83 research outputs found
Unusual metachronous isolated inguinal lymph node metastasis from adenocarcinoma of the sigmoid colon
No full textAbstract This study aimed to describe an unusual case of metachronous isolated inguinal lymph nodes metastasis from sigmoid carcinoma. A 62-year-old man was referred to our department because of an obstructing sigmoid carcinoma. Colonoscopy showed the obstructing lesion at 30 cm from the anal verge and abdominal CT revealed a sigmoid lesion infiltrating the left lateral abdominal wall. The patient underwent a colonic resection extended to the abdominal wall. Histology showed an adenocarcinoma of the colon infiltrating the abdominal wall with iuxtacolic nodal involvement. Thirty three months after surgery abdominal CT and PET scan revealed a metastatic left inguinal lymph node involvement. The metastatic lymph node was found strictly adherent to the left iliac-femoral artery and encompassing the origin of the left inferior epigastric artery. Histology showed a metachronous nodal metastasis from colonic adenocarcinoma. Despite metastastic involvement of inguinal lymph node from rectal cancer is a rare but well known clinical entity, to the best of our knowledge, this is the first report of inguinal metastasis from a carcinoma of the left colon. Literature review shows only three other similar reported cases: two cases of inguinal metastasis secondary to adenocarcinoma of the cecum and one case of axillary metastasis from left colonic carcinoma. A metastatic pathway through superficial abdominal wall lymphatic vessels could be possible through the route along the left inferior epigastric artery. The solitary inguinal nodal involvement from rectal carcinoma could have a more favorable prognosis. In the case of nodal metastasis to the body surface lymph nodes from colonic carcinoma, following the small number of such cases reported in the literature, no definitive conclusions can be drawn.</p
A New Convenient Synthetic Method and Preliminary Pharmacological Characterization of Triazinediones as Prokineticin Receptor Antagonists
No full textA new efficient synthetic method to obtain prokineticin receptor antagonists based on the triazinedione scaffold is described. In this procedure the overall yield improves from 13% to about 54%, essentially for two factors: 1) N-(chlorocarbonyl) isocyanate is no more used, it represents the yield limiting step with an average yield not exceeding 30%. 2) The Mitsunobu reaction is not involved in the new synthetic scheme avoiding the use of time and solvent consuming column chromatography. All synthesized triazinediones were preliminary pharmacologically screened in vivo for their ability to reduce the Bv8-induced thermal hyperalgesia. In this assay all compounds displayed EC50 values in the picomolar-subpicomolar range, some triazinediones containing a 4-halogen substituted benzyl group in position 5 showed the best activity. The analogues containing a 4-fluorine atom (PC-7) and a 4-bromobenzyl group (PC-25) resulted 10 times more potent than the reference PC-1 that bears a 4-ethylbenz
Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions
No full textCurrent therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. Pursuing on our investigation on potential anti HIV multi-target agents we have designed and synthesized a small library of biphenylhydrazo 4-arylthiazoles derivatives and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity. In particular, compound 2-{3-[(2-{4-[4-(hydroxynitroso)phenyl]-1,3-thiazol-2-yl} hydrazin-1-ylidene) methyl]-4-methoxyphenyl} benzamide bromide (EMAC2063) was the most potent towards RNaseH (IC50 = 4.5 mM)- and RDDP (IC50 = 8.0 mM) HIV RT-associated functions
Homology modeling of a Class A GPCR in the inactive conformation: A quantitative analysis of the correlation between model/template sequence identity and model accuracy
No full textPublished in final edited form as: J Mol Graph Model. 2016 November ; 70: 140–152. doi:10.1016/j.jmgm.2016.10.004.With the present work we quantitatively studied the modellability of the inactive state of Class A G protein-coupled receptors (GPCRs). Specifically, we constructed models of one of the Class A GPCRs for which structures solved in the inactive state are available, namely the β2 AR, using as templates each of the other class members for which structures solved in the inactive state are also available. Our results showed a detectable linear correlation between model accuracy and model/template sequence identity. This suggests that the likely accuracy of the homology models that can be built for a given receptor can be generally forecasted on the basis of the available templates. We also probed whether sequence alignments that allow for the presence of gaps within the transmembrane domains to account for structural irregularities afford better models than the classical alignment procedures that do not allow for the presence of gaps within such domains. As our results indicated, although the overall differences are very subtle, the inclusion of internal gaps within the transmembrane domains has a noticeable a beneficial effect on the local structural accuracy of the domain in question
Larger tumor size predicts nodal involvement in patients with follicular thyroid carcinoma
No full textAims and background Lymph node metastases are rare in patients with follicular thyroid carcinoma, with an average incidence of 5.5% of all cases reported in the literature. In the present study we focused on the search for risk factors predictive of lymph node involvement in patients with follicular thyroid carcinoma to plan the most appropriate management and follow-up. Methods and study design We carried out a cross-sectional study among patients with follicular thyroid carcinoma and lymph node metastasis at diagnosis and patients without lymph node involvement. From January 1998 to April 2008, 930 patients underwent thyroidectomy in our surgical department for a variety of thyroid disorders, 420 (45.2%) of them for a differentiated thyroid carcinoma. The medical records of 55 patients with histological diagnosis of follicular thyroid carcinoma were analyzed. Results Four patients (7.3%) had lymph node metastasis from follicular thyroid carcinoma at presentation in both the lateral and central neck compartments. Mean tumor size was significantly greater for follicular thyroid carcinomas with nodal metastasis (5.1 ± 1.4 cm) than for those without nodal involvement (3.0 ± 1.2 cm, P <0.010). Among factors supposed to influence the presence of nodal metastasis at diagnosis (age, gender, tumor size, multifocality, tumor poorly differentiated, tumor widely invasive, vascular invasion, thyroid capsular invasion, and extra thyroid invasion), tumor size larger than 4.0 cm was the only factor retained in the multivariate statistical model. Conclusions Lymph node dissection must be planned only in the case of large follicular thyroid carcinomas. Since follicular carcinoma is usually diagnosed postoperatively, more attention should be paid to nodal involvement in the tumor re-staging during follow-up of those patients with tumors larger than 4.0 cm in diameter. </jats:sec
Measurement of the effective B0s→K+K− lifetime
No full textA measurement of the effective lifetime is presented using approximately 37 pb−1 of data collected by LHCb during 2010. This quantity can be used to put constraints on contributions from processes beyond the Standard Model in the meson system and is determined by two complementary approaches as
τKK=1.440±0.096 (stat)±0.008 (syst)±0.003 (model) ps
HALOGENATED TRIAZINEDIONES BEHAVE AS ANTAGONISTS OF PKR1: IN-VITRO AND IN-VIVO PHARMACOLOGICAL CHARACTERIZATION
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Conservation hints for Pinna nobilis from a century-old genetic time capsule
No full text: The noble pen shell, Pinna nobilis, is an iconic marine bivalve endemic to the Mediterranean Sea, playing a key role as an ecosystem engineer. Over the past century, it has faced severe threats from overharvesting, pollution, and catastrophic mass mortality events. This study analysed 119 mitochondrial COI gene sequences from historical (1700s, 1920s, 1970s, 1990s) and modern (2000s) samples, including survivors of recent mass mortality crises. We standardised a protocol to extract DNA from ancient byssus samples over a century old and dated the emergence of the mitochondrial lineages of Pinna nobilis, uncovering its evolutionary history in unprecedented detail. Our findings suggest two main temporal origins for the species' genetic variation: (i) a group of modern lineages directly descended from Pinna nobilis early ancestors originating 2.5 mya, and (ii) a large group derived from the first Pleistocene radiation of the species, approximately 1.5 mya. Importantly, our research depicts the evolutionary response of Pinna nobilis to three major challenges in the last century: human overexploitation, pollution, and environmental changes. Our results highlight the species' remarkable resilience, likely mediated by Pleistocene genetic traits, whose persistence over time mainly depends on the maintaining of a high effective population size to ensure successful recruitment
Predominance of Methicillin Resistant Staphylococcus Aureus -ST88 and New ST1797 causing Wound Infection and Abscesses.
No full textAlthough there has been a worldwide emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA), little is known about the molecular epidemiology of MRSA in Tanzania. In this study, we characterized MRSA strains isolated from clinical specimens at the Bugando Medical Centre, Tanzania, between January and December 2008. Of 160 S. aureus isolates from 600 clinical specimens, 24 (15%) were found to be MRSA. Besides molecular screening for the Panton Valentine leukocidin (PVL) genes by PCR, MRSA strains were further characterized by Multi-Locus Sequence Typing (MLST) and spa typing. Despite considerable genetic diversity, the spa types t690 (29.1%) and t7231 (41.6%), as well as the sequence types (ST) 88 (54.2%) and 1797 (29.1%), were dominant among clinical isolates. The PVL genes were detected in 4 isolates; of these, 3 were found in ST 88 and one in ST1820. Resistance to erythromycin, clindamicin, gentamicin, tetracycline and co-trimoxazole was found in 45.8%, 62.5%, 41.6%, 45.8% and 50% of the strains, respectively. We present the first thorough typing of MRSA at a Tanzanian hospital. Despite considerable genetic diversity, ST88 was dominant among clinical isolates at the Bugando Medical Centre. Active and standardized surveillance of nosocomial MRSA infection should be conducted in the future to analyse the infection and transmission rates and implement effective control measures
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