Validity of single‐point assessments for determining leg pulse wave velocity in sitting and supine positions

There has been a great deal of interest into the effects of prolonged sitting on lower limb vascular function. However, most studies use flow‐mediated dilation which is technically challenging. A simpler technique is pulse wave velocity (PWV) which can be estimated at any single arterial site of interest using a number of different calculations (Bramwell–hill [PWV_BH], β‐stiffness index [PWV_β] and blood flow [PWV_BF]). Findings from this technique would be better inferred if they compare to a standard criterion 2‐point PWV assessment. The current study used ultrasound to determine which estimation of single‐point PWV is most valid. The criterion was traditional ECG‐gated 2‐point (superficial femoral [SF]‐posterior tibialis [PT]) PWV. Single‐point estimates were calculated at the SF and PT arteries in both supine and seated positions. Single‐point PWV was considered valid if the aSEE was <1.0 m·s. Findings show that for both postural positions, the absolute standard error of estimates (aSEE) criterion of <1.0 m·s was not achieved in either the PT or SF arteries using any of the single‐point PWV calculations. However, single‐point calculations consistently demonstrated the lowest error at the SF artery using PWV_β in both supine (SF aSEE = 1.7 vs. PT 2.7 m·s) and seated (SF aSEE = 1.5 vs. PT 3.0 m·s) positions. All single‐point ΔPWV (supine – seated) calculations were higher in sitting, with PWV_β having the closest agreement (ΔSF aSEE 1.7 m·s) to the 2‐point criterion. Single‐point PWV calculations do not directly reflect regional 2‐point PWV. However, they are sensitive to change when moving from supine to seated positions.     

Evidence Regarding the Treatment of Denture Stomatitis

Denture stomatitis is a common inflammatory condition affecting the mucosa underlying complete dentures. It is associated with denture microbial biofilm, poor denture hygiene, poor denture quality, and nocturnal denture use. Numerous treatment methodologies have been used to treat stomatitis; however, a gold standard treatment has not been identified. The aim of this systematic review is to report on the current knowledge available in studies representing a range of evidence on the treatment of denture stomatitis.     

CXC chemokine expression and synthesis in skeletal muscle during ischemia/reperfusion

BACKGROUND: The chemokines keratinocyte-Derived Cytokine (KC) and macrophage inflammatory protein (MIP)-2, murine equivalents of human interleukin 8, have been implicated in remote injury after acute hind limb ischemia/reperfusion (I/R). These studies were designed to determine whether the cytokines responsible for remote tissue injury are also synthesized and accumulate in the ischemic or reperfused hind limb. METHODS: B6, 129SF2/J mice were subjected to either 3 hours of unilateral hind limb ischemia alone (IA) or 3 hours of ischemia followed by 4 or 24 hours of reperfusion (I/R). After IA or I/R, experimental and control (nonischemic) contralateral hind limbs were harvested for analysis of protein content, messenger RNA (mRNA), tissue edema, and viability. RESULTS: IA did not increase KC or MIP-2 mRNA or protein levels. In contrast, I/R resulted in a 15- and 10-fold increase in KC mRNA after 4 and 24 hours of reperfusion, respectively. KC protein levels were increased 10-fold after 4 hours of reperfusion and 30-fold after 24 hours (vs IA or sham; P < .001). MIP-2 mRNA transiently increased 42-fold after 4 hours of reperfusion but decreased to basal levels after 24 hours of reperfusion. Despite the relative increase in MIP-2 mRNA by 4 hours of reperfusion, significantly increased (8- to 10 fold) MIP-2 protein levels were not detected until 24 hours of reperfusion only in the reperfused limbs. Tissue edema was increased significantly (P < .01) compared with sham after just 4 hours of reperfusion and remained increased at 24 hours. Tissue viability decreased 52% after 4 hours of reperfusion and did not change significantly by 24 hours. CONCLUSIONS: Skeletal muscle is a site of significant ongoing chemokine synthesis during reperfusion. The persistent increase in muscle chemokine levels at 24 hours of reperfusion was not associated with increased edema or injury. The role of these chemokines during reperfusion may be further investigated by local or oral administration of chemokines or chemokine receptor antagonists. CLINICAL RELEVANCE: I/R injury remains an important clinical problem across a variety of surgical specialties. In the critical care arena, serum levels of proinflammatory cytokines have been useful in predicting the mortality associated with acute respiratory distress syndrome and sepsis. In this article, the data presented indicate that murine skeletal muscle produces potent proinflammatory neutrophil and macrophage chemokines during reperfusion, but not during ischemia. These findings suggest that measurement of tissue and/or serum levels of chemokines during reperfusion may be an important adjunct to predicting tissue injury along with ongoing inflammation during the clinical course of reperfusion injury. Within the vascular system, severe inflammatory responses are usually associated with thrombotic events. New techniques to noninvasively image thrombin activation (by using magnetic resonance imaging) in reperfused limbs may coincide with the pattern of murine skeletal muscle chemokine expression in humans. The data suggest that reperfusion is when chemokine mRNA and protein synthesis increase. Within the time periods studied in these experiments, the chemokine component of the inflammatory response remained in the reperfused, rather than the systemic nonreperfused, tissue. This observation may underestimate the degree of the systemic response to ischemia because the single mouse hind limb represents only 7% of the mouse total body area, whereas the human limb represents nearly 18% of the adult body area. Despite this shortcoming, these data provide potential temporal and quantitative information regarding the location and magnitude of chemokine synthesis in skeletal muscle during reperfusion.     

Effects of dietary phenethyl isothiocyanate, ellagic acid, sulindac and calcium on the induction and progression of N-nitrosomethylbenzylamine-induced esophageal carcinogenesis in rats

The potential inhibitory effects of phenethyl isothiocyanate(PEITC), ellagic acid (EA), sulindac and supplemental dietarycalcium (SDC) on N-nitrosomethylbenzylamine (NMBA)-induced esophagealcarcinogenesis were evaluated in rats utilizing an abbreviated(5 week) NMBA treatment protocol which allowed administrationof the putative inhibitors throughout the experiment (i.e. beginning2 weeks prior to NMBA treatment) or following completion ofNMBA dosing only. PEITC at 500 p.p.m. significantly inhibitedtumor incidence and multiplicity when given before and during,but not following, NMBA treatment. Neither sulindac at 125 p.p.m.nor SDC (2% versus 0.5% in control diet) inhibited tumor developmentwhen given during or following NMBA treatment. EA, which wasadministered only following NMBA treatment, significantly reducedthe incidence (66.7% versus 100% in NMBA controls), but notthe multiplicity, of esophageal tumors at the high-dose (4000p.p.m.) level. Together these findings indicate that: (i) PEITCselectively inhibits the induction but not the subsequent progressionof NMBA-induced esophageal tumors; (ii) EA may repress esophagealtumor development when administered following NMBA treatment;(iii) at the doses administered, neither sulindac nor SDC possesssignificant inhibitory activity against NMBA-induced esophagealcarcinogenesis in the rat.     

O6-Methyguanine levels and histopathological changes in the rat esophagus and liver following single and repeated administration of N-nitrosomethylbenzylamin

In this study we investigated the time course of O⁶-methylguanine(O⁶-meGua) levels and concomitant histo-pathological effectsin the rat esophagus and liver following single and repeateds.c administration of the esophagus-specific carcinogen N-nitrosomethylbenzylamine(NMBA). The primary purpose of this study was to determine ifdifferences in the induction and/or persistence of O⁶-meGuamight account for differences in the tumorigenicity of NMBAobserved with treatment regimens of 0.5 mg/kg/ dose, 3 doses/weekfor 5 weeks (a proven tumorigenic regimen) and 1.67 mg/kg/dose,3 doses/week for 2 weeks (an essentially non-tumorigenic regimen).Results of the single dose experiment indicated that enzymaticactivation of NMBA in the rat esophagus was not dose limited,at least at doses up to and including 5.0 mg/kg. Results ofthe repeated dose experiment demonstrated that the non-tumorigenicNMBA regimen produced significantly higher levels of esophagealO⁶meGua compared with the tumorigenic NMBA regimen. During the2 week treatment period of the non-tumorigenic regimen esophagealO⁶-meGua levels decreased progressively, but remained significantlyhigher than in the tumorigenic regimen. In contrast, the relativelylower O⁶-meGua levels of the tumorigenic regimen remained essentiallyunchanged during the course of treatment At 72 h following conclusionof dosing no O⁶-meGua was detected in the esophagi of rats treatedwith either regimen. Microscopic examinations revealed thatthe non-tumorigenic NMBA regimen produced a marked cytotoxiceffect on the esophageal epithelium, while microscopic esophagealchanges observed with the tumorigenic regimen were generallyless severe. In the liver O⁶meGua was detected in only a fewrats and no remarkable microscopic pathology was observed inthis organ. Together these findings indicate that: (i) abbreviatedNMBA treatment induces tumors in the rat esophagus only at levelsthat induce DNA damage without causing extensive cytotoxicity;(ii) the lack of NMBA tumorigenicity in the rat liver may bedue, at least in part, to the rapid and efficient repair ofO⁶-meGua adducts, coupled with the lack of necrosis and compensatorycell division in this organ.     

Benzo[b]fluoranthene: tumorigenicity in strain A/J mouse lungs, DNA adducts and mutations in the Ki-ras oncogene

The polycyclic aromatic hydrocarbon benzo[b]fluoranthene (B[b]F)is a pervasive constituent of environmental combustion products.We sought to examine the lung tumorigenic activity of B[b]Fin strain A/J mice, to study the relationship between formationand decay of B[b]F-DNA adducts and to examine mutations in theKi-ras proto-oncogene in DNA from B[b]F-induced tumors. Micewere given i.p. injections of 0, 10, 50, 100 or 200 mg/kg bodywt and lung adenomas were scored after 8 months. B[b]F inducedsignificant numbers of mouse lung adenomas in a dose-relatedfashion, with the highest dose (200 mg/kg) yielding 6.95 adenomas/mouse, with 100% of the mice exhibiting an adenoma. In micegiven tricaprylin, the vehicle control, there were 0.60 adenomas/mouse,with 55% of the mice exhibiting an adenoma. Based on dose, B[b]Fwas less active than benzo[