Development of glycopeptide-intermediate resistance by Staphylococcus aureus leads to attenuated infectivity in a rat model of endocarditis.

Glycopeptide-intermediate resistant Staphylococcus aureus (GISA) are characterized by multiple changes in the cell wall and an altered expression of global virulence regulators. We investigated whether GISA are affected in their infectivity in a rat model of experimental endocarditis. The glycopeptide-susceptible, methicillin-resistant S. aureus M1V2 and its laboratory-derived GISA M1V16 were examined for their ability to (i) adhere to fibrinogen and fibronectin in vitro, (ii) persist in the bloodstream after intravenous inoculation, (iii) colonize aortic vegetations in rats, and (iv) compete for valve colonization by co-inoculation. Both GISA M1V16 and M1V2 adhered similarly to fibrinogen and fibronectin in vitro. In rats, GISA M1V16 was cleared faster from the blood (P < 0.05) and required 100-times more bacteria than parent M1V2 (10(6) versus 10(4)CFU) to infect 90% of vegetations. GISA M1V16 also had 100 to 1000-times lower bacterial densities in vegetations. Moreover, after co-inoculation with GISA M1V16 and M1V2Rif, a rifampin-resistant variant of M1V2 to discriminate them in organ cultures, GISA M1V16 was out-competed by the glycopeptide-susceptible counterpart. Thus, in rats with experimental endocarditis, GISA showed an attenuated virulence, likely due to a faster clearance from the blood and a reduced fitness in cardiac vegetations. The GISA phenotype appeared globally detrimental to infectivity.

Bucket-handle tear of the triangular fibrocartilage complex : case report of a complex peripheral injury with separation of the distal radioulnar ligaments from the articular disc.

Palmer previously proposed a classification system of triangular fibrocartilage complex (TFCC) injuries that proved to be useful in directing clinical management. However, dorsal peripheral tears (variants of class 1C) were not described and have rarely been reported in the literature since. We herewith present a rare case of bucket-handle tear of the TFCC. To our knowledge, this is the first case demonstrating partial separation of both the palmar and dorsal distal radioulnar ligaments (DRULs) from the articular disc. The particular wrist magnetic resonance (MR) arthrographic findings of this unusual complex peripheral TFCC tear (a variant of both class 1B and 1C) were nicely appreciated upon sagittal reformatted images.

Cholinergic neurons of fetal rat telencephalon in aggregating cell culture respond to NGF as well as to protein kinase C-activating tumor promoters.

Serum-free aggregating cell cultures of fetal rat telencephalon treated with the potent tumor promoter phorbol 12-myristate 13-acetate (PMA) showed a dose-dependent, persistent stimulation of the enzymes choline acetyltransferase (ChAT), glutamic acid decarboxylase and glutamine synthetase. After elimination of the proliferating cells by treatment of the cultures with Ara-C (0.4 microM) only the cholinergic marker enzyme, ChAT, could be stimulated by tumor promoters. The non-promoting phorbol ester, 4 alpha-phorbol 12,13-didecanoate proved to be inactive in these cultures, whereas the potent non-phorbol tumor promoter, mezerein, produced an even greater stimulatory effect than PMA. Since PMA and mezerein are potent and specific activators of protein kinase C, the present results suggest a role for this second messenger in the development of cholinergic telencephalon neurons. Stimulation of ChAT required prolonged exposure (48 h) of the cultures to PMA and the responsiveness of the cholinergic neurons to the tumor promoters decreased with progressive cellular maturation. The cholinergic telencephalon neurons showed the same pattern of responsiveness for tumor promoters as for nerve growth factor (NGF). However, the combined treatment with NGF and either PMA or mezerein produced an additive stimulatory effect, suggesting somewhat different mechanisms of action.

Photodynamic induced uptake of liposomal doxorubicin to rat lung tumors parallels tumor vascular density.

BACKGROUND: Visudyne®-mediated photodynamic therapy (PDT) at low drug/light conditions has shown to selectively enhance the uptake of liposomal doxorubicin in subpleural localized sarcoma tumors grown on rodent lungs without causing morphological alterations of the lung. The present experiments explore the impact of low-dose PDT on liposomal doxorubicin (Liporubicin™) uptake to different tumor types grown on rodent lungs. MATERIAL AND METHODS: Three groups of Fischer rats underwent subpleural generation of sarcoma, mesothelioma, or adenocarcinoma tumors on the left lung. At least five animals of each group (sarcoma, n = 5; mesothelioma, n = 7; adenocarcinoma, n = 5) underwent intraoperative low-dose (10 J/cm(2) at 35 mW/cm(2) ) PDT with 0.0625 mg/kg Visudyne® of the tumor and the lower lobe. This was followed by intravenous (IV) administration of 400 µg Liporubicin™. After a circulation time of 60 min, the tumor-bearing lung was processed for HPLC analyses. At least five animals per group underwent the same procedure but without PDT (sarcoma, n = 5; mesothelioma, n = 5; adenocarcinoma, n = 6). Five untreated animals per group underwent CD31 immunostaining of their tumors with histomorphometrical assessment of the tumor vascularization. RESULTS: Low-dose PDT significantly enhanced Liporubicin™ uptake to all tumor types (sarcoma, P = 0.0007; mesothelioma, P = 0.001; adenocarcinoma, P = 0.02) but not to normal lung tissue compared to IV drug administration alone. PDT led to a significantly increased ratio of tumor to lung tissue drug uptake for all three tumor types (P < 0.05). However, the tumor drug uptake varied between tumor types and paralleled tumor vascular density. The vascular density was significantly higher in sarcoma than in adenocarcinoma (P < 0.001) and mesothelioma (P < 0.001), whereas there was no significant difference between adenocarcinoma and mesothelioma. CONCLUSION: Low-dose Visudyne®-mediated PDT selectively enhances the uptake of systemically administered liposomal doxorubicin in tumors without affecting the drug uptake to normal lung. However, drug uptake varied significantly between tumor types and paralleled tumor vascular density.

Transección pancreática mediante un nuevo dispositivo asistido por radiofrecuencia en un modelo porcino de pancreatectomía distal laparoscópica: estudio de factibilidad

La morbilitat relacionada amb el desenvolupament de la fístula pancreàtica postoperatòria (FP) posteriorment a realitzar una pancreatectomia distal persisteix elevada. Hem realitzat un treball experimental per a avaluar la factibilitat de la realització de la transecció pancreàtica mitjançant un nou dispositiu assistit per radiofreqüència en un model porcí de pancreatectomia distal laparoscòpica (PDL). S’ha realitzat PDL en 10 animals avaluant com a variable principal el desenvolupament de FP i com a variables secundàries paràmetres relacionats amb l’aparició de complicacions intra o postoperatòries. Els resultats obtinguts suggereixen la factibilitat de la realització de la transecció pancreàtica mitjançant el dispositiu assistit per radiofreqüència.

Muscimol-induced death of GABAergic neurons in rat brain aggregating cell cultures.

During brain development, spontaneous neuronal activity has been shown to play a crucial role in the maturation of neuronal circuitries. Activity-related signals may cause selective neuronal cell death and/or rearrangement of neuronal connectivity. To study the effects of sustained inhibitory activity on developing inhibitory (GABAergic) neurons, three-dimensional primary cell cultures of fetal rat telencephalon were used. In relatively immature cultures, muscimol (10 microns), a GABAA receptor agonist, induced a transient increase in apoptotic cell death, as evidenced by a cycloheximide-sensitive increase of free nucleosomes and an increased frequency of DNA double strand breaks (TUNEL labeling). Furthermore, muscimol caused an irreversible reduction of glutamic acid decarboxylase activity, indicating a loss of GABAergic neurons. The muscimol-induced death of GABAergic neurons was attenuated by the GABAA receptor blockers bicuculline (100 microns) and picrotoxin (100 microns), by depolarizing potassium concentrations (30 mM KCl) and by the L-type calcium channel activator BAY K8644 (2 microns). As compared to the cholinergic marker (choline acetyltransferase activity), glutamic acid decarboxylase activity was significantly more affected by various agents known to inhibit neuronal activity, including tetrodotoxin (1 micron), flunarizine (5 microns), MK 801 (50 microns) and propofol (40 microns). The present results suggest that the survival of a subpopulation of immature GABAergic neurons is dependent on sustained neuronal activity and that these neurons may undergo apoptotic cell death in response to GABAA autoreceptor activation.

Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimer. A basis for new therapeutic strategies.

The peroxisome proliferator-activated receptor gamma (PPARgamma) is highly expressed in the colon mucosa and its activation has been reported to protect against colitis. We studied the involvement of PPARgamma and its heterodimeric partner, the retinoid X receptor (RXR) in intestinal inflammatory responses. PPARgamma(1/)- and RXRalpha(1/)- mice both displayed a significantly enhanced susceptibility to 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis compared with their wild-type littermates. A role for the RXR/PPARgamma heterodimer in the protection against colon inflammation was explored by the use of selective RXR and PPARgamma agonists. TNBS-induced colitis was significantly reduced by the administration of both PPARgamma and RXR agonists. This beneficial effect was reflected by increased survival rates, an improvement of macroscopic and histologic scores, a decrease in tumor necrosis factor alpha and interleukin 1beta mRNA levels, a diminished myeloperoxidase concentration, and reduction of nuclear factor kappaB DNA binding activity, c-Jun NH(2)-terminal kinase, and p38 activities in the colon. When coadministered, a significant synergistic effect of PPARgamma and RXR ligands was observed. In combination, these data demonstrate that activation of the RXR/PPARgamma heterodimer protects against colon inflammation and suggest that combination therapy with both RXR and PPARgamma ligands might hold promise in the clinic due to their synergistic effects.

El papel del ganglio centinela en la evolución del cáncer de colon

L'afectació o no dels ganglis limfàtics influeix en el pronòstic dels pacients amb càncer de còlon i en la decisió de realitzar tractament adjuvant, en conseqüència, l'estudi particular ganglionar podria aportar informació que determinés canvis en el maneig d'aquests pacients. Per dur a terme aquest estudi podria ajudar-nos la determinació del gangli sentinella. La seva detecció permetria la identificació d'un petit nombre de ganglis representatius de l'estat histopatològic del territori ganglionar i en ells realitzar un estudi més exhaustiu amb l'objectiu d'aconseguir un estadiatge més exacte dels pacients, amb possible transcendència en el tractament adjuvant requerit.

¿La cirugía laparoscópica en el cáncer de colon presenta iguales resultados en pacientes octogenarios? Influencia de factores diferenciales

S'ha realitzat un estudi retrospectiu sobre 593 pacients dividits en tres grups d'edat (&70, 70-79 i& 80 anys), intervinguts de càncer de còlon per laparoscòpia entre 1998 i 2009. S’han analitzat totes les variables preoperatòries, la morbiditat associada a cada grup d’edat tant mèdica como quirúrgica i les dades intraoperatòries, per a obtenir la taxa de complicacions postoperatòries. Després dels resultats s'ha objectivat que l'índex de complicacions en el grup de majors de 80 anys és major a causa del gran nombre de factors de risc pel que fa als més joves.

Influència de l’índex de massa corporal i de la massa muscular en el desenvolupament de lesió muscular en pacients sotmesos a cirurgia de colon laparoscòpica

La cirurgia oncològica de colon i recte via laparoscòpica requereix una posició quirúrgica especial, la de litotomia modificada (posició Lloyd-Davies), Trendelemburg &30º, i side dret o esquerre depenent del costat de la cirurgia. En aquest tipus de posició quirúrgica les lesions musculars per reperfusió de les extremitats inferiors son complicacions que s’han que considerar, sobretot en cirurgies de llarga durada i en pacients amb factors de risc com obesitat, diabetis i enolisme crònic. En pacients obesos està descrit que l’ índex de massa muscular elevat pot ser un factor de risc a l’hora de desenvolupar lesions musculars tant per reperfussió com per compressió prolongada, que poden arribar al síndrome compartimental.

Distribution and genesis of the RFRP-producing neurons in the rat brain: comparison with melanin-concentrating hormone- and hypocretin-containing neurons.

Prepro-RFRP-containing neurons have recently been described in the mammalian brain. These neurons are only found in the tuberal hypothalamus. In this work, we have provided a detailed analysis of the distribution of cells expressing the RFRP mRNA, and found them in seven anatomical structures of the tuberal hypothalamus. No co-expression with melanin-concentrating hormone (MCH) or hypocretin (Hcrt), that are also described in neurons of the tuberal hypothalamus, was observed. Using the BrdU method, we found that all RFRP cell bodies are generated between E13 and E14. Thus, RFRP neurons form a specific cell population with a complex distribution pattern in the tuberal hypothalamus. However, they are generated in one peak. These observations are discussed with data concerning the distribution and genesis of the MCH and Hcrt cell populations that are also distributed in the tuberal hypothalamus.