Left Paraduodenal Hernia in a Young Patient with Recurrent Abdominal Pain: A Case Report and Short Literature Review.

BACKGROUND Internal hernias are a rare cause of small bowel obstruction in patients, which usually have a long history of mild abdominal symptoms, sometimes leading to emergency surgery due to acute abdominal pain. Occasionally, it takes a long time to make the correct diagnosis because of symptoms vagueness and transience of typical imaging findings; at times, a definitive diagnosis is possible only through surgery, especially in cases of acute presentations in a low-resource setting where high-performance diagnostic equipment may be unavailable. CASE REPORT We report the case of a young male patient with a long history of mild abdominal symptoms and some episodes of acute abdominal pain.

Patient factors predicting early dropout from psychiatric outpatient care for borderline personality disorder.

Despite obvious clinical need, factors underlying early treatment discontinuation among 'real world' borderline personality disorder (BPD) patients are still unknown. This study investigates individual characteristics that can predict early ( View Article and Find Full Text PDF

Two-year follow-up of borderline personality disorder patients in Italy: a preliminary report on prognosis and prediction of outcome.

Background And Aims: Few naturalistic studies have examined the course of borderline personality disorder (BPD) outside North American countries. The aim of this prospective study was to investigate remission rate, changes in the level of BPD psychopathology and outcome prediction in a sample (n = 46) of Italian BPD outpatients over a two-year follow-up.

Method: Two years after baseline, remission rate from BPD and changes in the severity of BPD psychopathology were investigated.

Mild mental retardation in a child with a de novo interstitial deletion of 15q21.2q22.1: a comparison with previously described cases.

We report on a child with mild mental retardation, hypotelorism, blepharophimosis, face slight asymmetry and partial hypoplasia of corpus callosum, with an interstitial deletion of a chromosome 15. The deletion was molecularly characterized by array-CGH and FISH techniques. This rearrangement has a 7.

[Gastrointestinal stromal tumors: report of three cases and review of the literature].

Gastrointestinal stromal tumours are the most common mesenchimal tumours of the gastrointestinal tract. Diagnosis of these tumours is difficult to establish, because symptoms are vague and traditional diagnostic tests are not specific. Natural history remains poorly defined and many criteria have been correlated with prognosis; for instance, some authors have found that GIST localization influences clinical behavior, that has not been confirmed by other authors; actually, tumour size, mitotic rate and complete resection seem to be the main prognostic factors.

Gene expression profiling reveals cross-talk between melanoma and fibroblasts: implications for host-tumor interactions in metastasis.

Host-tumor interaction is considered critical in carcinogenesis, tumor invasion, and metastasis. To explore the reciprocal effects of host-tumor interaction, we developed a system to assess the gene expression patterns of A2058 human melanoma cells cocultured in fibrillar collagen with HS-68 primary human fibroblasts. The gene expression pattern of the cocultured A2058 cells was only modestly affected, whereas the HS-68 fibroblast gene expression pattern was significantly altered.

Synthesis and evaluation of new tripeptide phosphonate inhibitors of MMP-8 and MMP-2.

The phosphotryptophan derivative l-Pro-l-Leu-l-(P)Trp(OH)(2) (2b) was reported as the first example of left-hand-sideLeft-hand-side inhibitors: inhibitors that bind in the unprime region of the enzyme active site, in reference to the convention of drawing the unprimed residues of a peptide substrate on the left side. [R.P.

The enol tautomer of indole-3-pyruvic acid as a biological switch in stress responses.

Indole-3-pyruvic acid (IPA) undergoes in solutions to the keto-enol tautomerism, which appears responsible of its pharmacological effects, as only the enol tautomer is an easy target for oxygen free-radicals and can be transformed directly to kynurenic acid (KYNA). Contrary to expectations, the IPA enol tautomer is rather stable in mammalian tissues, due to the presence of specific tautomerases, favouring the formation of KYNA in the presence of free-radicals. Because of the synergistic effects between glucocorticoids, free-radicals and excitatory aminoacids in chronic stress, the enol tautomer of IPA and KYNA are proposed as physiological metabolites produced in order to shut-off the chronic stress cycle.

Molecular dynamics simulation of matrix metalloproteinase 2: fluctuations and time evolution of recognition pockets.

We report a molecular dynamics simulation study of a zinc-protease--gelatinase A or MMP2--which is a major target for drug design, being involved in tumor metastasis and other degenerative diseases. Two structures have been employed as starting conditions, one based on the crystal of multi-domain proMMP2, the other consisting of the catalytic domain only. The overall fold of the two models is maintained over the 1260 ps trajectory, enabling us to analyze correlations of fluctuations among domains, and to observe the presence of correlations within the catalytic domain in the multi-domain enzyme only, hence due to the presence of hemopexin and fibronectin domains.

In vivo functional dissection of human inner kinetochore protein CENP-C.

CENP-C is a fundamental component of the inner kinetochore plate and contributes to the formation of functional centromeres in eukaryotic organisms. Recruitment of CENP-C to kinetochore requires other centromere proteins, particularly CENP-A, CENP-H, and CENP-I. However, how CENP-C is correctly localized at the kinetochore is not clearly determined, mainly due to the functional variety of its domains, which hints at a complex recruitment mechanism.

Inhibition of contact hypersensitivity reaction to picryl chloride: effect of small molecular weight peptidomimetic compounds possessing inhibitory activity against metalloproteinases.

We have studied the effect of small molecular weight inhibitors of snake venom metalloproteinases (SVMP) and matrix metalloproteinases (MMPs) on the induction and effector phase of the contact hypersensitivity reaction (CHR) in a mouse model. Identification of nonsteroid small molecules is very important for the development of new anti-inflammatory drugs. The compounds that we tested were synthetically modified tripeptides (peptidomimetic compounds) POL-257, POL-509, POL-443, POL-491, and POL-647, with structures based on natural occurring peptides in snake venom.

CENP-C binds the alpha-satellite DNA in vivo at specific centromere domains.

CENP-C is a fundamental component of the centromere, highly conserved among species and necessary for the proper assembly of the kinetochore structure and for the metaphase-anaphase transition. Although CENP-C can bind DNA in vitro, the identification of the DNA sequences associated with it in vivo and the significance of such an interaction have been, until now, elusive. To address this problem we took advantage of a chromatin-immunoprecipitation procedure and applied this technique to human HeLa cells.

Modulation of the catalytic activity of neutrophil collagenase MMP-8 on bovine collagen I. Role of the activation cleavage and of the hemopexin-like domain.

The cleavage of bovine collagen I by neutrophil collagenase MMP-8 has been followed at pH 7.4, 37 degrees C. The behavior of the whole enzyme molecule (whMMP-8), displaying both the catalytic domain and the hemopexin-like domain, has been compared under the same experimental conditions with that of the catalytic domain only.

Role of p75 neurotrophin receptor in the neurotoxicity by beta-amyloid peptides and synergistic effect of inflammatory cytokines.

The neurodegenerative changes in Alzheimer's disease (AD) are elicited by the accumulation of beta-amyloid peptides (Abeta), which damage neurons either directly by interacting with components of the cell surface to trigger cell death signaling or indirectly by activating astrocytes and microglia to produce inflammatory mediators. It has been recently proposed that the p75 neurotrophin receptor (p75(NTR)) is responsible for neuronal damage by interacting with Abeta. By using neuroblastoma cell clones lacking the expression of all neurotrophin receptors or engineered to express full-length or various truncated forms of p75(NTR), we could show that p75(NTR) is involved in the direct signaling of cell death by Abeta via the function of its death domain.

Neurotrophin p75 receptor is involved in neuronal damage by prion peptide-(106-126).

In this work we have investigated the molecular basis of the neuronal damage induced by the prion peptide by searching for a surface receptor whose activation could be the first step of a cascade of events responsible for cell death. By using a human neuroblastoma cell line lacking all the neurotrophin receptors and derived clones expressing the full-length or truncated forms of the low affinity neurotrophin receptor (p75(NTR)), we have been able to demonstrate that the neuronal death induced by the prion protein fragment PrP-(106-126) is an active process mediated by a) the binding of the peptide to the extracellular region of p75(NTR), b) the signaling function of the intracytoplasmic region of the receptor, and c) the activation of caspase-8 and the production of oxidant species.

pH- and temperature-dependence of functional modulation in metalloproteinases. A comparison between neutrophil collagenase and gelatinases A and B.

Metalloproteases are metalloenzymes secreted in the extracellular fluid and involved in inflammatory pathologies or events, such as extracellular degradation. A Zn(2+) metal, present in the active site, is involved in the catalytic mechanism, and it is generally coordinated with histidyl and/or cysteinyl residues of the protein moiety. In this study we have investigated the effect of both pH (between pH 4.

Uridine induces differentiation in human neuroblastoma cells via protein kinase C epsilon.

Uridine metabolism has an important role in the physiopathology of the nervous system. In this paper, we have explored the effects of exogenous uridine on LAN-5 human neuroblastoma cells. Cells were exposed to uridine for 4 days and cell proliferation, neurite outgrowth, and 160 kDa neurofilament (NF) expression were the parameters measured.

Cleavage of bovine collagen I by neutrophil collagenase MMP-8. Effect of pH on the catalytic properties as compared to synthetic substrates.

The enzymatic processing of bovine collagen I by neutrophil collagenase (MMP-8) has been monitored at 37 degrees C, envisaging the occurrence of multiple intermediate steps, following the initial cleavage, which leads to the formation of (1/4) and (3/4) fragments. Further, the first cleavage event has been investigated at 37 degrees C as a function of pH, and catalytic parameters have been obtained through a global analysis of steady-state kinetic data, such as to get an overall consistent picture of k(cat)/K(m), k(cat), and K(m). These data have been compared with those obtained from the catalysis by MMP-8 of two synthetic fluorogenic substrates under the same experimental conditions.

Clinical experiences with the use of indole-3-pyruvic acid.

In the last few years, Indol-3-pyruvic acid (IPA) has been subjected to 5 pilot clinical trials in volunteers and a phase II study on patients affected by anxiety, with or without sleep problems. Overall, results indicated a very good safety profile, relief from anxiety and a better quality of sleep in patients treated with IPA. Moreover, the drug showed no withdrawal signs, but positive effects on mood, improving feelings of relaxation, calmness and happiness.

Managing ankle injuries in the emergency department.

We review the anatomy and physiology of the ankle joint with attention to the structures most likely to be injured. We discuss the epidemiology of ankle injuries and their physical and radiographic evaluation, including the Ottawa Ankle Rules. Treatment, consultation, and pitfalls are followed by more specific discussions of tendonitis, Achilles tendon injury, tendonous subluxations, tarsal tunnel syndrome, sonovial impingement, and injury to the os trigonum.

Structures of adamalysin II with peptidic inhibitors. Implications for the design of tumor necrosis factor alpha convertase inhibitors.

Crotalus adamanteus snake venom adamalysin II is the structural prototype of the adamalysin or ADAM family comprising proteolytic domains of snake venom metalloproteinases, multimodular mammalian reproductive tract proteins, and tumor necrosis factor alpha convertase, TACE, involved in the release of the inflammatory cytokine, TNFalpha. The structure of adamalysin II in noncovalent complex with two small-molecule right-hand side peptidomimetic inhibitors (Pol 647 and Pol 656) has been solved using X-ray diffraction data up to 2.6 and 2.

2 angstrom X-ray structure of adamalysin II complexed with a peptide phosphonate inhibitor adopting a retro-binding mode.

The search of reprolysin inhibitors offers the possibility of intervention against both matrixins and ADAMs. Here we report the crystal structure of the complex between adamalysin II, a member of the reprolysin family, and a phosphonate inhibitor modeled on an endogenous venom tripeptide. The inhibitor occupies the primed region of the cleavage site adopting a retro-binding mode.

Processing of pro-tumor necrosis factor-alpha by venom metalloproteinases: a hypothesis explaining local tissue damage following snake bite.

Venom-induced necrosis is a common local debilitating sequela of bites by many vipers, frequently resulting in severe permanent scarring and deformity. Antivenoms are not effective under these circumstances unless administered within a few minutes of the bite; this is unlikely to occur in the rural tropics where most victims take a long time to reach medical care. We have shown that two venom zinc metalloproteinases (jararhagin from Bothrops jararaca venom and a metalloproteinase from Echis pyramidum leakeyi venom) successfully cleaved the recombinant glutathione-S-transferase-tumor necrosis factor-alpha fusion protein (GST-TNF-alpha) substrate to form biologically active TNF-alpha which was shown to be neutralized by ovine TNF-alpha Fab antibodies.