Are patients with knee osteoarthritis aware that platelet-rich plasma is a treatment option?

Osteoarthritis (OA) is a prevalent joint disease, particularly affecting the knees. This condition is often managed through various treatments, including intra-articular injections such as corticosteroids (CS), hyaluronic acid (HA), and platelet-rich plasma (PRP). PRP has shown promising outcomes in recent studies although it does lack strong endorsement in some clinical guidelines due to inconsistent results and lack of standardized results.

Dopaminergic Control of Inflammation and Glycemia in Sepsis and Diabetes.

Most preclinical treatments for sepsis failed in clinical trials in part because the experimental models of sepsis were performed on healthy animals that do not mimic septic patients. Here, we report that experimental diabetes worsens glycemia, inflammation, and mortality in experimental sepsis. Diabetes increases hyperglycemia, systemic inflammation, and mortality in sepsis.

A sphingosine-1 phosphate agonist (FTY720) limits trauma/hemorrhagic shock-induced multiple organ dysfunction syndrome.

Background: Trauma/hemorrhagic shock (T/HS) is one of the major consequences of battlefield injury as well as civilian trauma. FTY720 (sphingosine-1-phosphate agonist) has the capability to decrease the activity of the innate and adaptive immune systems and, at the same time, maintain endothelial cell barrier function and vascular homeostasis during stress. For this reason, we hypothesize that FTY720, as part of resuscitation therapy, would limit T/HS-induced multiple organ dysfunction syndrome in a rodent T/HS model.

Testosterone depletion or blockade in male rats protects against trauma hemorrhagic shock-induced distant organ injury by limiting gut injury and subsequent production of biologically active mesenteric lymph.

Background: We tested the hypothesis that testosterone depletion or blockade in male rats protects against trauma hemorrhagic shock-induced distant organ injury by limiting gut injury and subsequent production of biologically active mesenteric lymph.

Methods: Male, castrated male, or flutamide-treated rats (25 mg/kg subcutaneously after resuscitation) were subjected to a laparotomy (trauma), mesenteric lymph duct cannulation, and 90 minutes of shock (35 mm Hg) or trauma sham-shock. Mesenteric lymph was collected preshock, during shock, and postshock.

Anticoagulants influence the in vitro activity and composition of shock lymph but not its in vivo activity.

Many models of trauma-hemorrhagic shock (T/HS) involve the reinfusion of anticoagulated shed blood. Our recent observation that the anticoagulant heparin induces increased mesenteric lymph lipase activity and consequent in vitro endothelial cell cytotoxicity prompted us to investigate the effect of heparin-induced lipase activity on organ injury in vivo as well as the effects of other anticoagulants on mesenteric lymph bioactivity in vitro and in vivo. To investigate this issue, rats subjected to trauma-hemorrhage had their shed blood anticoagulated with heparin, the synthetic anticoagulant arixtra (fondaparinux sodium), or citrate.

Loss of the intestinal mucus layer in the normal rat causes gut injury but not toxic mesenteric lymph nor lung injury.

There is substantial evidence that gut barrier failure is associated with distant organ injury and systemic inflammation. After major trauma or stress, the factors and mechanisms involved in gut injury are unknown. Our primary hypothesis is that loss of the intestinal mucus layer will result in injury of the normal gut that is exacerbated by the presence of luminal pancreatic proteases.

Calcium entry inhibition during resuscitation from shock attenuates inflammatory lung injury.

Trauma and hemorrhagic shock (T/HS) induce a systemic inflammatory response syndrome (SIRS). Neutrophils (polymorphonuclear leukocytes [PMN]) and other cells involved in acute lung injury (ALI) are activated by Ca2+ entry. Thus, inhibiting Ca2+ entry might attenuate post-traumatic lung injury.

Trauma-shock-induced gut injury and the production of biologically active intestinal lymph is abrogated by castration in a large animal porcine model.

Although small animal rodent studies indicate that there is a sexual dimorphism in the resistance to organ injury after trauma-hemorrhagic shock (T/HS), confirmatory studies are largely lacking in more clinically relevant large animal species. Thus, we tested the hypothesis that castration would reduce the susceptibility of adult minipigs to gut injury and abrogate the production of biologically active intestinal (mesenteric) lymph after T/HS. The hemodynamic response to T/HS was similar between castrated and noncastrated minipigs.

Resistance of the female, as opposed to the male, intestine to I/R-mediated injury is associated with increased resistance to gut-induced distant organ injury.

We tested the hypothesis that the female intestine is more resistant to gut I/R injury than the male intestine by comparing the effects of the isolated pure gut I/R superior mesenteric artery occlusion (SMAO) model on gut morphology and whether SMAO-induced distant organ injury (lung, bone marrow [BM], neutrophils, and red blood cells [RBCs]) would differ between male and proestrus female rats. At 6 or 24 h after SMAO or sham SMAO, gut injury, lung permeability, pulmonary neutrophil sequestration, RBC deformability, and BM RBC and white blood cell progenitor growth were measured, as was the ability of the plasma from these rats to activate naive rat neutrophils. At both 6 and 24 h after SMAO, the female rats had significantly less intestinal injury and reduced gut-induced lung injury, BM suppression, RBC dysfunction, and neutrophil activation than male rats subjected to SMAO.

Amiloride moderates increased gut permeability and diminishes mesenteric lymph-mediated priming of neutrophils in trauma/hemorrhagic shock.

Background: Amiloride, an inhibitor of Na+/H+ exchangers and Na+ channels has been shown recently to ameliorate both gut and lung injury in rats subjected to a combined insult of trauma and hemorrhagic shock (T/HS). We have shown previously that mesenteric lymph duct ligation prevents T/HS-induced lung endothelial injury and neutrophil activation, suggesting that toxic inflammatory factors originating from the gut and carried in the lymph are responsible for the lung injury observed after T/HS. This study investigates whether the protective effect of amiloride against T/HS-induced lung injury was associated with decreased lymph toxicity and gut permeability.

Gut-lymph hypothesis of systemic inflammatory response syndrome/multiple-organ dysfunction syndrome: validating studies in a porcine model.

Background: Trauma-hemorrhagic shock (T/HS) mesenteric lymph from rats has multiple biological properties and appears to cause organ injury via the activation of neutrophils and endothelial cells. As the next step in testing the potential clinical relevance of these rodent studies, we utilized a swine T/HS model to determine whether the intestinal lymph results observed in the rodent could be replicated in swine. A porcine model was chosen because the pig and human cardiovascular and gastrointestinal physiology are similar.

Neutrophil activation is modulated by sex hormones after trauma-hemorrhagic shock and burn injuries.

Recent literature indicates that females are more resistant to shock-, trauma-, and sepsis-induced immune dysfunction and organ injury than are males. Consequently, using trauma-hemorrhagic shock (T/HS) and burn models, we tested whether the neutrophil response to trauma occurred in a sexually dimorphic fashion and, if so, the role of sex hormones. Neutrophil activation, as reflected by CD11b expression and respiratory burst activity, was increased to a greater extent in male rats than in female rats after T/HS or burn injury.

Amiloride combined with small-volume resuscitation with hypertonic saline is superior in ameliorating trauma-hemorrhagic shock-induced lung injury in rats to the administration of either agent alone.

Objective: Recognition of the limitations of standard crystalloid resuscitation has led to exploration for alternative resuscitation strategies that might better prevent the development of trauma-hemorrhage-induced organ dysfunction and systemic inflammation. Thus, the goal of this study was to compare the effects of two resuscitation strategies alone and in combination with that of standard resuscitation with Ringer's lactate. These two strategies were intravenous injection of amiloride, an inhibitor of Na/H exchange and epithelial Na channels, and resuscitation with hypertonic saline.

Store-operated calcium channel inhibition attenuates neutrophil function and postshock acute lung injury.

Background: A wide variety of neutrophil (PMN) functions are regulated by cytosolic calcium concentration. Calcium channel blockade might therefore decrease postshock inflammation but could also limit important cardiovascular compensations. PMN Ca2+ entry occurs, however, through store-operated calcium entry (SOCE) channels rather than the voltage operated (L-type) channels that regulate cardiovascular tone.

Sex hormones modulate distant organ injury in both a trauma/hemorrhagic shock model and a burn model.

Background: Emerging data suggest a gender dimorphism in resistance and susceptibility to distant organ injury after mechanical and thermal trauma. The aim of this study was to determine the role that testosterone and estradiol play in modulating resistance or susceptibility to distant organ injury, and whether their effects were associated with differences in the production of nitric oxide.

Methods: Adult male, female, castrated male, and ovariectomized female Sprague-Dawley rats were given intraperitoneal pentobarbital sodium anesthesia and subjected to trauma/sham shock or trauma/hemorrhagic shock (T/HS).

A study of the biologic activity of trauma-hemorrhagic shock mesenteric lymph over time and the relative role of cytokines.

Background: Gut-derived factors in intestinal lymph have been recently shown to cause lung injury, activate neutrophils, and injure endothelial cells in rats subjected to hemorrhagic shock (T/HS). However, the time course of the appearance and disappearance of these factors in intestinal lymph is unclear. Thus the goal of this study was to characterize the biologic activity of T/HS lymph collected at various times during and after shock.

Mesenteric lymph from burned rats induces endothelial cell injury and activates neutrophils.

Objective: Our previous studies indicated that mesenteric lymph duct ligation prevented burn-induced lung injury. Thus, the goal of the present study was to begin to investigate potential mechanisms of this protective effect.

Design: Prospective animal study with concurrent control.

Intestinal bacterial overgrowth induces the production of biologically active intestinal lymph.

Objective: We have previously documented that gut-derived lymph from rats subjected to trauma plus hemorrhagic shock (T/HS) is injurious to vascular endothelial cells and activates neutrophils (PMNs), two key events in postshock organ injury. Because T/HS leads to gut injury, intestinal bacterial overgrowth, and the loss of gut barrier function, the relative role of gut injury as opposed to intestinal bacterial overgrowth per se in the pathogenesis of biologically active intestinal lymph is unclear. We therefore studied whether mesenteric lymph can injure endothelial cells and/or active PMNs in an intestinal bacterial overgrowth model where there is no gut injury (monoassociation).

Factors in intestinal lymph after shock increase neutrophil adhesion molecule expression and pulmonary leukosequestration.

Background: Because the ischemic gut may produce factors that initiate systemic inflammation, we tested the hypothesis that factors released from the gut into the mesenteric lymphatics increase neutrophil (PMN) adhesion molecule expression after trauma and shock.

Methods: At 1 and 4 hours after hemorrhagic shock (30 mm Hg x 90 minutes) plus trauma (laparotomy) (T/HS) or sham-shock (T/SS), with or without mesenteric lymph duct ligation, PMN CD11b and CD18 expression was assessed in male rats. In additional rats, mesenteric lymph samples were tested for their ability to increase PMN CD11b expression in vitro.

Serine proteases are involved in the pathogenesis of trauma-hemorrhagic shock-induced gut and lung injury.

The objective of this work was to test the hypothesis that Intraluminal serine proteases are involved in trauma-hemorrhagic shock (T/HS)-induced intestinal and lung injury. Male Sprague-Dawley rats were administrated the serine protease inhibitor (6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfate, Nafamostat) either intraluminally into the gut or intravenously after a laparotomy (trauma) and then subjected to 90 min of hemorrhagic shock (T/HS) or sham shock (T/SS). Intestinal and lung injury was assessed at 3 h after resuscitation with Ringer's lactate solution.

Hypertonic saline resuscitation limits neutrophil activation after trauma-hemorrhagic shock.

There is evidence suggesting that the ischemic gut is a major source of factors that lead to neutrophil activation, and that neutrophil activation can be reduced by hypertonic saline resuscitation. Thus, we tested whether trauma-hemorrhagic shock-induced neutrophil activation can be reduced by hypertonic saline resuscitation, as well as whether hypertonic saline reduces the ability of mesenteric lymph from shocked animals to activate neutrophils. Male Sprague-Dawley rats subjected to trauma (laparotomy), plus 90 min of shock [mean arterial pressure (MAP) MAP = 30 mmHg] or sham shock were resuscitated with Ringer's lactate or 7.