Predicting postoperative nausea and vomiting in patients undergoing oral and maxillofacial surgery.

A common predictive measure of postoperative nausea and vomiting (PONV) is the Apfel score. Although tested in many different operations, it has not been tested extensively in oral and maxillofacial surgery (OMFS). This study was designed to determine whether it applied to OMFS and whether there were other factors in this population that would improve its accuracy. A retrospective chart review was carried out on a randomly selected group of patients who had OMFS during a 10-month period. In addition to the Apfel score risk factors, PONV data were collected in relation to type of anesthetic induction and maintenance, type of surgery, use of maxillomandibular fixation (MMF), use of opioids, and anesthesia and surgery times. One-hundred and sixty-seven patients were included in the analysis; 24% had nausea and 11% had nausea and vomiting. Patients who had orthognathic or temporomandibular joint surgery had the highest rate of PONV. Young age, anesthesia and operation time, and use of MMF were also associated with increased PONV. Adding age, MMF or limited postoperative mouth opening, and surgery type to the Apfel score should make it more predictive in OMFS.

Modulation of Inflammation as a Way of Delaying Alzheimer's Disease Progression: The Diet's Role.

BACKGROUND: Most of the recent reports suggest that inflammatory mediators play a central role in the etiopathogenesis of Alzheimer's disease (AD) and that the conditions leading to a chronic low-grade inflammation, such as stress, depression, obesity and metabolic syndrome, increase the odds of developing Mild Cognitive Impairment (MCI) and AD. Microglia cells are the main actors in the AD process: stimuli from the microenvironment may induce microglia cells to switch to a classically activated inflammatory phenotype M1, or, on the contrary to an alternatively activated M2 phenotype characterized by the secretion of different types of cytokines. Many attempts are currently being made in order to delay the progression of AD by reducing inflammatory mechanisms underlying the disease. Several studies support a relationship among neuroinflammation and nutrients, foods or dietary patterns, taking into account the synergistic or antagonistic biochemical interactions among nutrients as well as the different food sources of the same nutrient. Natural antioxidant and anti-inflammatory compounds found in plant foods, such as fruits, particularly berries (such as strawberry, blueberry, blackcurrant, blackberry, blueberry and mulberry) have been shown to exert neuroprotective activity. It is still unclear whether the dietary bioactive compounds enter the Blood Brain Barrier (BBB) playing a direct antiinflammatory or pro-inflammatory effect on microglia and/or other Central Nervous System (CNS) cells. Another hypothesis is that they may trigger a peripheral reaction that induce indirectly a CNS' response. The subsequent synthesis of cytokines may drive microglia polarization by different ways. So, via an indirect route microglia detects and responds to immune-to-brain signaling. CONCLUSION: This review summarizes current evidence about the potential mechanisms of the interaction among diet, neuroinflammation and AD.

The effect of fibroblast growth factor 15 deficiency on the development of high fat diet induced non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a form of non-alcoholic fatty liver disease (NAFLD) characterized by steatosis, inflammation, and fibrosis often associated with metabolic syndrome. Fibroblast growth factor 15 (FGF15), an endocrine factor mainly produced in the distal part of small intestine, has emerged to be a critical factor in regulating bile acid homeostasis, energy metabolism, and liver regeneration. We hypothesized that FGF15 alters the development of each of the listed features of NASH. To test this hypothesis, four-week old male Fgf15-/- and their corresponding wild-type (WT) mice were fed either a high fat diet (HFD) or a control chow diet for six months. The results confirmed that HFD feeding for six months in WT mice recapitulated human NASH phenotype, including macrovesicular steatosis, inflammation, and fibrosis. Whereas FGF15 deficiency had no effect on the severity of liver steatosis or inflammation, it was associated with decreased liver fibrosis. Furthermore, FGF15 deficiency resulted in abnormal bile acid homeostasis, increased insulin resistance, increased HFD-induced serum triglycerides, decreased inductions of hepatic cholesterol content by HFD, and altered gene expression of lipid metabolic enzymes. These data suggest that FGF15 improves lipid homeostasis and reduces bile acid synthesis, but promotes fibrosis during the development of NASH.

Toxicodynamics of rigid polystyrene microparticles on pulmonary gas exchange in mice: implications for microemboli-based drug delivery systems.

The toxicodynamic relationship between the number and size of pulmonary microemboli resulting from uniformly sized, rigid polystyrene microparticles (MPs) administered intravenously and their potential effects on pulmonary gas exchange were investigated. CD-1 male mice (6-8 weeks) were intravenously administered 10, 25 and 45 µm diameter MPs. Oxygen hemoglobin saturation in the blood (SpO(2)) was measured non-invasively using a pulse oximeter while varying inhaled oxygen concentration (F(I)O(2)). The resulting data were fit to a physiologically based non-linear mathematical model that estimates 2 parameters: ventilation-perfusion ratio (V(A)/Q) and shunt (percentage of deoxygenated blood returning to systemic circulation). The number of MPs administered prior to a statistically significant reduction in normalized V(A)/Q was dependent on particle size. MP doses that resulted in a significant reduction in normalized V(A)/Q one day post-treatment were 4000, 40,000 and 550,000 MPs/g for 45, 25 and 10 µm MPs, respectively. The model estimated V(A)/Q and shunt returned to baseline levels 7 days post-treatment. Measuring SpO(2) alone was not sufficient to observe changes in gas exchange; however, when combined with model-derived V(A)/Q and shunt early reversible toxicity from pulmonary microemboli was detected suggesting that the model and physical measurements are both required for assessing toxicity. Moreover, it appears that the MP load required to alter gas exchange in a mouse prior to lethality is significantly higher than the anticipated required MP dose for effective drug delivery. Overall, the current results indicate that the microemboli-based approach for targeted pulmonary drug delivery is potentially safe and should be further explored.

Opinions of American and Swedish orthodontists about the role of erupting third molars as a cause of dental crowding.

OBJECTIVE: To compare the opinions of Swedish orthodontists and American orthodontists regarding the association between third molar eruption and dental crowding. MATERIALS AND METHODS: A survey was distributed to Swedish orthodontists (n = 230) asking their views on the force exerted by erupting third molars, its relationship to crowding, and their recommendations for prophylactic removal. Results were compared with those from a similar study conducted in the United States. Chi square analysis was used to determine differences in responses to questions between Swedish and American orthodontists. P < or = .05 was considered significant. RESULTS: Both Swedish and American orthodontists believed that lower third molars were more likely than upper third molars to cause force (65% and 58% for Swedish and American orthodontists, respectively) and crowding (42% and 40%, respectively). No statistically significant differences were seen between the answers of American and Swedish orthodontists regarding the role of upper and lower third molars in causing crowding. Although only 18% of Swedish orthodontists "generally" or "sometimes" recommended prophylactic removal of mandibular third molars, 36% of American orthodontists "generally" or "sometimes" recommended removal (P < .0001). CONCLUSIONS: Most orthodontists in the United States and Sweden do believe that erupting lower third molars exert an anterior force; however, they also believe that these teeth "rarely" or "never" cause crowding of the dentition. The reason that more American orthodontists recommend prophylactic removal of mandibular third molars remains unexplained.

Comparison of the stress direction on the TMJ in patients with class I, II, and III skeletal relationships.

OBJECTIVE: To assess the relationship between skeletal morphology and stress direction on the temporomandibular joint (TMJ) by a two-dimensional rigid body spring model (RBSM). DESIGN: Lateral cephalograms were analyzed and the information was processed with a fortran analysis program. SETTING AND SAMPLE POPULATION: The subjects were 149 patients (54 men and 95 women, mean age 21.8 +/- 5.9 years) from Kanazawa University Hospital and the School of Dentistry, Virginia Commonwealth University. Of the 149 cases, 48 were skeletal class I, 54 were class II, and 47 were class III. The patients had no TMJ symptoms or abnormalities. OUTCOME MEASURE: The force vector on the condyle, its direction (Ph angle), the degree of the vector (Ph) and the displacement vector (u, v), and the rotational angle (theta) of the mandibular body were calculated by RBSM. RESULTS: The direction of the force vector (Ph angle) on the condyle was 24.83 degrees +/- 4.67 degrees in the class II group, 21.04 degrees +/- 5.59 degrees in the class I group, and 19.58 +/- 7.57 degrees in the class III group. The Ph angle of the class II group was significantly larger than those of the class I and III groups (p < 0.05). CONCLUSIONS: This study suggests that differences in skeletal patterns induce differences in stress distribution on the TMJ; the morphology of the TMJ was also associated with stress direction and distribution on the condyle.

A comparative study of mandibular fractures in the United States and Turkey.

This study compared the data on mandibular fractures that occurred in a city in the United States and one in Turkey between 1991 and 2000. The 210 Turkish patients had 252 mandibular fractures, whereas the 665 US patients had 1042 mandibular fractures. Males accounted for 84% (560 patients) and females for 16% (105 patients) of the cases in the US. The male:female ratio was 5.5:1. In Turkey, males accounted for 76% (160 patients) and females for 24% (50 patients) of cases. The male:female ratio was 3.2:1. Assault (53.7%) was the most common cause of fracture in the US, whereas in Turkey the most common cause was a motor vehicle accident (36.2%). The most common site of mandibular fracture in the US was the angle (27.57%); in Turkey the most common site was the body (28.97%). Many of these variations may be related to socioeconomic, cultural and environmental differences between the two countries.

Mechanisms underlying reduced responsiveness of neonatal neutrophils to distinct chemoattractants.

Potential mechanisms underlying impaired chemotactic responsiveness of neonatal neutrophils were investigated. Two distinct chemoattractants were compared: bacterially derived N-formyl-methionyl-leucyl-phenylalanine (fMLP) and a unique chemotactic monoclonal antibody, designated DL1.2, which binds to a neutrophil antigen with an apparent molecular mass of 120 kDa. Chemotaxis of neutrophils toward fMLP, as well as DL1.2, was reduced in neonates when compared with adult cells. This did not appear to be a result of decreased fMLP receptor or DL1.2 antigen expression by neonatal neutrophils. fMLP, but not DL1.2, induced a rapid increase in intracellular calcium in adult and neonatal cells, which reached a maximum within 30 s. The calcium response of cells from neonates to fMLP was reduced when compared with adult cells, and an unresponsive subpopulation of neonatal neutrophils was identified. NF-kappaB nuclear binding activity induced by fMLP and DL1.2, as well as expression of the p65 NF-kappaB subunit and IkappaB-alpha, was also significantly reduced in neonatal cells, when compared with adult cells. In contrast, although fMLP, but not DL1.2, activated p42/44 and p38 mitogen-activated protein (MAP) kinases in neutrophils, no differences were observed between adults and neonates. Chemotaxis of adult and neonatal neutrophils toward fMLP and DL1.2 was also blocked to a similar extent by inhibitors of phosphatidylinositol 3-kinase, as well as an inhibitor of NF-kappaB. These findings indicate that reduced chemotactic responsiveness in neonatal neutrophils is a result of, at least in part, aberrations in chemoattractant-induced signaling. However, the biochemical pathways mediating this defect appear to be related to the specific chemoattractant.

Tissue injury following inhalation of fine particulate matter and hydrogen peroxide is associated with altered production of inflammatory mediators and antioxidants by alveolar macrophages.

Hydrogen peroxide (H(2)O(2)) is present in the atmosphere at concentrations known to induce cell and tissue damage. However, inhaled H(2)O(2) vapor should not reach the lower lung due to its high water solubility. It has been suggested that hygroscopic components of particulate matter (PM) may transport H(2)O(2) into the lower lung and induce tissue injury and this was investigated. Ammonium sulfate [(NH(4))(2)SO(4)] was selected as a model for fine atmospheric PM. Treatment of female Sprague-Dawley rats with (NH(4))(2)SO(4) (429 or 215 microg/m(3); 0.3-0.4 microm mass median diameter) or H(2)O(2) (10, 20, or 100 ppb) alone or in combination for 2 h had no major effect on bronchoalveolar lavage fluid cell number or viability or on protein content or lactate dehydrogenase levels, either immediately or 24 h after exposure, relative to air-exposed rats. However, electron microscopy revealed increased numbers of neutrophils in pulmonary capillaries adhered to the vascular endothelium in rats treated with the combination of (NH(4))(2)SO(4) + H(2)O(2). Exposure of rats to (NH(4))(2)SO(4) + H(2)O(2) also resulted in tumor necrosis factor-alpha (TNF-alpha) production by alveolar macrophages. This was observed immediately and 24 h after exposure. Immediately after inhalation of (NH(4))(2)SO(4) + H(2)O(2), a transient increase in production of superoxide anion by alveolar macrophages was observed. In contrast, nitric oxide production by cells from rats exposed to (NH(4))(2)SO(4) + H(2)O(2) or H(2)O(2) alone was decreased, and this persisted for 24 h. Decreases in nitric oxide may be due to superoxide anion-driven formation of peroxynitrite. In this regard, nitrotyrosine, an in vivo marker of peroxynitrite, was detected in lung tissue after exposure of rats to (NH(4))(2)SO(4) + H(2)O(2) or H(2)O(2). We also found that expression of the antioxidant enzyme heme oxygenase-1 by stimulated alveolar macrophages was increased following exposure of rats to (NH(4))(2)SO(4) + H(2)O(2). Taken together, these studies demonstrate that the biological effects of inhaled fine PM are augmented by H(2)O(2). Moreover, tissue injury induced by fine PM may be related to altered production of cytotoxic mediators by alveolar macrophages.

Functional heterogeneity in liver and lung macrophages.

Although initially considered merely "scavenger cells" that participate in immunologic responses only after B and T lymphocytes have performed their biological tasks, more recent evidence suggests that macrophages play a key role in host defense as well as in the maintenance of normal tissue structure and function. For macrophages to perform their biological functions, they must be activated. This involves up-regulation of an array of signaling pathways resulting in altered gene expression and increased biochemical and functional activity. Macrophages have been identified in almost all tissues of the body. However, the basal activity of these cells, as well as their ability to respond to inflammatory mediators, varies considerably with their location. In addition, even within a particular tissue, there is evidence of macrophage heterogeneity. The largest populations of macrophages in the body are located in the liver and lung. Because of the unique attributes of these tissues, hepatic and pulmonary macrophages play essential roles not only in nonspecific host defense but also in the homeostatic responses of these tissues. In this review, the functional and biochemical activities of macrophages localized in the liver and lungs are compared. Evidence suggests that these represent distinct cell populations with unique functions and responsiveness to inflammatory agents.

Depression, pain, exposure to stressful life events, and long-term outcomes in temporomandibular disorder patients.

PURPOSE: This study investigated the role of psychological factors in temporomandibular disorders (TMD). Orofacial pain patients' pretreatment levels of depression, disability caused by pain, and exposure to stressful life events were measured, and differences on these variables between temporomandibular joint (TMJ) disease patients and patients whose pain was of muscular origin (MPD) were evaluated. The use of these variables and patient diagnostic status in predicting response to treatment in a subsample of these patients was also evaluated. PATIENTS AND METHODS: Before undergoing treatment, 258 patients were administered the Beck Depression Inventory (BDI), the Pain Disability Index (PDI), and the Social Readjustment Rating Scale (SRRS). Follow-up data on pain disability, current level of pain, depression, and satisfaction with treatment were obtained on 48 of these patients who were contacted at varying intervals after completing treatment. RESULTS: BDI scores obtained at the outset of treatment were significantly elevated and were positively correlated with SRRS and PDI scores. MPD patients had higher SRRS, BDI depression, and PDI pain disability scores than TMJ patients, and differences between the 2 groups in pain disability were greatest in areas that are often sources of interpersonal stress. Among follow-up patients, PDI scores declined after treatment, with MPD patients showing greater decreases than TMJ patients. Independent of patients' diagnostic status, their pretreatment PDI scores were predictive of their pain level at follow-up and were inversely related to their degree of satisfaction with treatment at follow-up; their pretreatment BDI scores were predictive of their depression level at follow-up. CONCLUSIONS: The findings are consistent with previous research indicating a link between emotional dysfunction and TMD and are largely supportive of the conclusion that psychological factors play a more pronounced role when pain is of muscular origin. Promising behavioral interventions are available for TMD patients in whom psychological factors appear to be playing a significant role.

Prooxidant and antioxidant functions of nitric oxide in liver toxicity.

In response to tissue damage and inflammation induced by a variety of xenobiotics including acetaminophen, carbon tetrachloride, ethanol, galactosamine, and endotoxin, as well as disease states such as viral hepatitis, and postischemic and regenerative injury, the liver produces large quantities of nitric oxide. Indeed, nearly all cell types in the liver including hepatocytes, Kupffer cells, stellate cells, and endothelial cells have the capacity to generate nitric oxide. Thus, these cells, as well as infiltrating leukocytes, may indirectly augment tissue injury. In many models of liver damage, nitric oxide and its oxidation products such as peroxynitrite contribute to the injury process by directly damaging the tissue or by initiating additional immunologic reactions that result in damage. In some models, nitric oxide donors or peroxynitrite can mimic the cytotoxic actions of liver toxins. Moreover, agents that prevent the generation of nitric oxide or antioxidants that bind reactive nitrogen intermediates, or knockout mice with reduced capacity to produce nitric oxide, are protected from xenobiotic-induced tissue injury. In contrast, there have been reports that blocking nitric oxide production enhances xenobiotic-induced tissue injury. This has led to the concept that nitric oxide either inactivates proteins critical for xenobiotic-induced tissue injury or acts as an antioxidant, reducing cellular levels of cytotoxic reactive oxygen intermediates. Whether or not nitric oxide or secondary oxidants generated from nitric oxide act as mediators of tissue injury or protect against toxicity is likely to depend on the precise targets of these reactive nitrogen intermediates, as well as levels of superoxide anion present and the extent to which tissue injury is mediated by reactive oxygen intermediates. In addition, as toxicity is a complex process involving a variety of cell types and many soluble mediators, the contribution of each of these factors must be taken into account when considering the role of nitric oxide as a determinant of tissue injury.

Minimal amidine structure for inhibition of nitric oxide biosynthesis.

Pharmacological modulation of nitric oxide synthase activity has been achieved using structural analogs of arginine. In the present studies, we demonstrated that the minimal amidine structure required for enzymatic inhibition is formamidine. We found that the production of nitric oxide by primary cultures of rat hepatocytes and several mouse and human cell lines, including RAW 264.7 macrophages, PAM 212 keratinocytes, G8 myoblasts, S180 sarcoma, CX-1 human colon cells, and GH3 rat pituitary cells, was inhibited in a concentration- and time-dependent manner by formamidine. Formamidine was 2- to 6-fold more effective in inhibiting nitric oxide production in cells expressing inducible nitric oxide synthase (NOS2) than in a cell line expressing calcium-dependent neuronal nitric oxide synthase (NOS1). Whereas formamidine had no effect on gamma-interferon-induced expression of nitric oxide synthase protein, its enzymatic activity was blocked. Kinetic analysis revealed that formamidine acts as a simple competitive inhibitor with respect to arginine (K(i) formamidine approximately 800 microM). Using a polarographic microsensor to measure real-time flux of nitric oxide release from RAW 264.7 macrophages, formamidine was found to require 30-90 min to inhibit enzyme activity, suggesting that cellular uptake of the drug may limit its biological activity. Our data indicate that formamidine is an effective inhibitor of nitric oxide production. Furthermore, its low toxicity may make it useful as a potential therapeutic agent in diseases associated with the increased production of nitric oxide.

Pharmacologic therapy of persistent pulmonary hypertension of the newborn.

Persistent pulmonary hypertension of the newborn (PPHN) is a potentially life-threatening condition characterized by a failure of pulmonary vascular resistance to decrease adequately during the transition to extrauterine life. Inhaled nitric oxide, a vasodilator that acts selectively on the pulmonary circulation, has revolutionized the treatment of this condition. However, inhaled nitric oxide has not proven effective in all patients, particularly those with congenital diaphragmatic hernias or meconium aspiration syndrome. Furthermore, large clinical trials of inhaled nitric oxide have failed to demonstrate significant differences in mortality between nitric oxide-treated and control infants with PPHN. Other therapeutic approaches to PPHN have been limited by a relative lack of specificity for the pulmonary circulation, and have received much less attention. Pharmacologic approaches, including pulmonary surfactants, prostacyclin, endothelin antagonists, Ca(2+)-channel blockers, magnesium sulfate, and tolazoline, have exhibited varying degrees of efficacy in lowering pulmonary vascular pressures in humans and/or animals. A number of these agents are also effective when used in combination. For example, phosphodiesterase inhibitors have been reported to act synergistically with inhaled nitric oxide. Surfactants also appear to be useful in PPHN, particularly in patients with congenital diaphragmatic hernia, when used in combination with other therapies. Surfactant lavage and other novel therapies may also be effective in combination therapy of meconium aspiration syndrome. Further studies should be directed at defining the optimal therapies in specific clinical settings. Validation of multiple therapeutic modalities for PPHN, including inhaled nitric oxide, will allow for rational, combined vasodilator strategies that are specific for the underlying pathophysiology in each patient.