A minimal role for selectins in the recruitment of leukocytes into the inflamed liver microvasculature

A two-step paradigm for leukocyte recruitment has been established in a number of tissues including the mesentery, skin, and muscle, and necessitates an initial rolling step via the selectins before firm leukocyte adhesion via the integrins. In view of the many inflammatory diseases that involve the liver, we investigated the importance of rolling and the selectins in the hepatic microvasculature and compared the responses to that of the commonly used mesentery or cremaster microvasculature. We visualized the liver microvasculature using intravital microscopy and we determined that within the liver the majority of leukocytes adhere within the sinusoids (80%) in response to a chemotactic stimulus such as FMLP (20% in postsinusoidal venules) whereas leukocytes adhere exclusively within postcapillary venules in tissue like the mouse cremaster. In the sinusoids, the adhesive response to FMLP is not dependent upon selectins inasmuch as adhesion was not reduced in the sinusoidal vessels of P-selectin-deficient mice or E-selectin/P-selectin- deficient animals in the presence or absence of L-selectin antibody. No rolling or adhesion was detected in response to FMLP in the selectin-deficient cremaster microvasculature. Immunoneutralization of selectins with fucoidan in wildtype mice eliminated rolling and adhesion in the cremaster but failed to affect adhesion in the liver sinusoids in response to FMLP. More long-term leukocyte recruitment with lipopolysaccharide (4 h) was also impaired in the cremaster but not the liver microvasculature in selectin-deficient animals. Leukocyte adhesion in the sinusoids was reduced in P-selectin-deficient mice also lacking intercellular adhesion molecule-1 (ICAM-1). This study for the first time demonstrates that selectins are not an essential step for leukocyte recruitment into the inflamed liver microvasculature.     

Vascular clamping of the liver. Indications and limits

Control of bleeding during liver surgery is an essential prognostic factor for postoperative morbidity and mortality. Several well defined methods are currently available to ensure vascular occlusion, ranging from selective clamping of a segmental pedicle to total vascular exclusion of the liver. These methods of vascular control each have specific indications. However, they can induce ischaemia of the liver whose functional consequences, such as postoperative liver failure, are particularly severe in the case of prolonged ischaemia, affecting the remaining liver and in the presence of histological or functional alterations of the hepatic parenchyma. Selective methods of vascular control, only affecting the part of the liver to be resected, can be used systematically. In contrast, when the occlusion is not selective, they must be used sparingly, essentially in the case of bleeding from the parenchymal section, adopting the principal objective of the briefest possible total ischaemia. Minimization of bleeding must be weighed up against the consequences of ischaemia on the remaining liver, especially in the case of extensive hepatectomy, prolonged clamping and pathological non-neoplastic liver.     

Repair of congenital H-type vestibuloanorectal fistula through the posterior midsagittal approach: case report

In this study we attempt to evaluate the advantages and disadvantages of extracorporeal shock wave lithotripsy (ESWL) in situ versus retrograde stone manipulation before ESWL (ESWL+push back) in patients with proximal ureteral stones with regard to tissue damage and inflammatory processes. Several studies have revealed that C-reactive protein (CRP) is a useful marker for tissue damage and inflammation. Thirty patients following primary ESWL in situ, with residual calculi, were randomized to retreatment with ESWL in situ or ESWL+push back. Four of 15 patients in the ESWL+push back group demonstrated an increase in CRP levels after treatment compared with no significant increase in 15 patients in the ESWL in situ group. We conclude that ESWL+push back did not cause significantly higher CRP values than ESWL in situ. ESWL+push back may cause irritation, inflammation, and slight tissue damage in some cases; however, these effects are probably minor and would not contraindicate its use. The implications of this study are that serum CRP levels may be utilized to monitor tissue injury in patients undergoing auxiliary procedures.     

Powerlessness and HIV prevention among people who trade sex for drugs (''strawberries'')

Agonistic analogs of GnRH have emerged as effective drugs in the treatment of pelvic pain associated with endometriosis. Iatrogenic hypoestrogenism is the fundamental mechanism through which GnRH agonists induce regression of the exquisitely estrogen-dependent endometriotic lesions. The decrease in bone mass consistently observed in women on long-term GnRH agonist treatment has prompted regulatory agencies such as the FDA to approve the use of these drugs for a maximum of six months in the treatment of endometriosis. The very high recurrence rate of pelvic symptomatology after the interruption of medical therapy underlines the importance of strategies aiming at improving the safety of effective long-term treatments. Data has recently become available suggesting the existence of an ideal range of circulating estradiol levels which would maintain a normal bone metabolism and still cause atrophy of endometriotic lesions. Add-back regimens including estrogen preparations have been therefore studied with variable results. In strict analogy, as oral progestins have been shown to improve bone mass in postmenopausal women, regimens employing progestin add-back have been proposed. Our review describes most of the currently published studies employing these and other substances in association with the commonly used GnRH agonists in patients with symptomatic endometriosis.     

Characterization and localization of galanin receptors in human entorhinal cortex

The neuropeptide galanin (GAL) has a widespread distribution throughout the human cortex. The entorhinal cortex (ENT) plays a crucial role in the transfer of cortico-cortical information related to memory and displays severe degeneration in Alzheimer's disease (AD). However, very little is known about the pharmacology of the GAL receptor (GALR) in normal human ENT. Therefore, we pharmacologically visualized their distribution and characterized GALRs using in vitro receptor autoradiography and radioligand binding assays. Autoradiograms revealed intense GALR labeling, mainly in the substantia innominata, hypothalamus, the bed nucleus of the stria terminalis and within layers 2 and 4 of the ENT. Kinetic experiments showed that saturation of GALR sites by [125I]GAL (human) (hGAL) occurred within 2 h and that this binding readily reversed in the presence of a GTP analog, but not in the presence of excess unlabeled hGAL. Analysis of [125I]hGAL binding data from saturation experiments gave KD values of 98.6+/-21.6 pM, Bmax values of 52.9+/-32.4 fmol/mg protein and identified a high and low affinity state of the GALR. The presence of 5'-guanylylimidodiphosphate (GppNHp) or NaCl reduced the agonist labeling of hGALR in ENT membranes.