Transforming growth factor β (TGF-β ) has been shown to participate in the pathophysiology of diabetic complications. As shown most recently, TGF-β stimulates the expression of a distinct ...serine/threonine kinase (hSGK) which had previously been cloned as an early gene transcriptionally regulated by cell volume alterations. The present study was performed to elucidate transcription and function of hSGK in diabetic nephropathy. As shown by Northern blotting, an increase of extracellular glucose concentration increased hSGK mRNA levels in cultured cells, an effect qualitatively mimicked by osmotic cell shrinkage or treatment with TGF-β (2 μ g/liter), phorbol 12,13-didecanoate (1 μ M), or the Ca2+ionophore ionomycin (1 μ M) and blunted by high concentrations of nifedipine (10 and 100 μ M). In situ hybridization revealed that hSGK transcription was markedly enhanced in diabetic nephropathy, with particularly high expression in mesangial cells, interstitial cells, and cells in thick ascending limbs of Henle's loop and distal tubules. According to voltage clamp and tracer flux studies in Xenopus oocytes expressing the renal epithelial Na+channel ENaC or the mouse thick ascending limb Na+,K+,2Cl-cotransporter BSC-1, coexpression with hSGK stimulated ENaC and BSC-1 11-fold and 6-fold, respectively, effects reversed by kinase inhibitors staurosporine (1 μ M) and chelerythrine (1 μ M) and not elicited by inactive hSGK. In conclusion, excessive extracellular glucose concentrations enhance hSGK transcription, which in turn stimulates renal tubular Na+transport. These observations disclose an additional element in the pathophysiology of diabetic nephropathy.
Summary The purpose of this study was to investigate whether dental injury diagnoses may predict adverse outcomes occurring 102 weeks after trauma, and to evaluate whether the severity of adverse ...outcome is related to laser Doppler flowmetry (LDF) measurements of blood flow from teeth. In 309 trauma patients, 404 permanent maxillary incisors and the respective contralateral homologous control teeth were investigated clinically and radiographically, and by LDF to assess local blood flow values. Dental displacement injuries were classified as grade I (subluxation), grade II (lateral or extrusive luxation), and grade III (avulsion or intrusive luxation). Dental fracture injuries were classified as uncomplicated crown fractures, complicated crown fractures, and root fracture. An adverse outcome was defined as the presence of ‘periapical radiolucency and/or grey discolouration’. Significant increase in risk of an adverse outcome occurred with a grade II dental displacement injury (15·07 odds ratio; P = 0·000), a grade III dental displacement injury (28·33 odds ratio; P = 0·000), and a root fracture (106·25 odds ratio; P = 0·000). Blood flow measurements that were significantly associated with more severe outcome were blood flow levels of ≤3 perfusion units (PU; 170·72 odds ratio; P = 0·000), and those of >3 PU and ≤6 PU (76·71 odds ratio; P = 0·000). Diagnoses of displaced and root fractured teeth predicted dental injury patients who went on to show adverse treatment outcomes of splinting. Blood flow measurements from teeth were related to the severity of adverse outcome.
Aim To evaluate laser Doppler flowmetry (LDF) measurements of pulpal blood flow (PBF) and severity of dental injury.
Methodology The relationship between adverse outcomes and PBF measurements was ...analysed in 94 permanent maxillary incisors of 71 consecutive dental trauma patients. The diagnostic adverse outcome group was comprised of 72 incisors in 52 patients with a type I (loss of sensitivity), type II (loss of sensitivity and periapical radiolucency), or type III (loss of sensitivity, periapical radiolucency and grey discoloration of crown) diagnosis. The nonadverse outcome group consisted of 22 incisors in 19 patients with the finding of an absence of an adverse outcome. At each session, when an injured permanent maxillary incisor was recorded, a contralateral homologous tooth was used as a control. An ordinal stepwise regression was completed to assess the degree of association between PBF measurements and adverse outcomes
Results Using chi‐square analysis for pairwise comparison, a significant relationship between PBF measurements and types of adverse outcomes (χ2 =119.635, d.f. = 12, P = 0.000) was observed. PBF measurements that were significantly associated with more severe outcome were PBF levels of ≤3 perfusion units (PU) (119.1 odds ratio) (P = 0.000), and those of >3 PU and ≤6 PU (12.7 odds ratio) (P = 0.000).
Conclusions PBF measurements were related to the severity of adverse outcomes. Further studies are required to evaluate whether PBF measurements can predict dental injuries that progress to adverse treatment outcomes.
– Splinting of traumatically displaced permanent teeth has been described as an effective modality in the treatment of patients with dental injuries. The purpose of this study was to (i) investigate ...whether dental injury diagnosis may predict adverse outcomes occurring 96 weeks after splint removal, and (ii) evaluate whether the severity of adverse outcome is related to laser Doppler flowmetry (LDF) measurements of pulpal blood flow (PBF). In 206 trauma patients, 273 permanent maxillary incisors treated by repositioning and splinting, and the respective contralateral homologous control teeth were investigated clinically and radiographically, and by LDF to assess local PBF values. Dental displacement injuries were classified as grade I (subluxation), grade II (lateral or extrusive luxation) and grade III (avulsion or intrusive luxation). Outcomes were classified as ‘absence of loss of sensitivity, periapical radiolucency, and/or grey discolouration of crown’, type I (loss of sensitivity), type II (loss of sensitivity and periapical radiolucency or grey discoloration of crown) and type III (loss of sensitivity, periapical radiolucency and grey discoloration of crown). An adverse outcome was defined as the presence of ‘periapical radiolucency and/or grey discoloration’. A multiple logistic regression analysis was used to compute the odds ratio (OR) for dental displacement injury for adverse outcome (n = 69) vs non‐adverse outcome (n = 168). An ordinal stepwise regresssion was completed to assess the degree of association between PBF measurements and outcome groups. Significant increase in risk of an adverse outcome occurred with a grade II dental displacement injury (OR 14.3) (P = 0.000) and a grade III dental displacement injury (OR 19.9) (P = 0.000). PBF measurements that were significantly associated with more severe outcome were PBF levels of ≤3 perfusion units (PU) (OR 399.4) (P = 0.000), those of >3 PU and ≤6 PU (OR 100.5) (P = 0.000), and those of >6 PU and ≤9PU (OR 6.2) (P = 0.000). Diagnoses of displaced teeth predicted dental injury patients who went on to show adverse treatment outcomes of splinting. PBF measurements were related to the severity of adverse outcome.
The purpose of this study was to assess the prevalences of magnetic resonance (MR) imaging findings of internal derangement (ID) in temporomandibular joints (TMJs) without a specific clinical ...diagnosis of temporomandibular disorder (TMD), and to investigate whether in this TMJ group the variable of pain may be linked to MR imaging findings of ID. The study comprised 109 patients, who were assigned a clinical uni‐ or bilateral TMJ‐related diagnosis of `absence of TMD'. Bilateral sagittal and coronal MR images were obtained subsequently to establish the prevalence of TMJ ID. An MR imaging diagnosis of ID was found in 99 (55·9%) of the 177 TMJs investigated. About 30·3% of the closed mouth‐related TMJ positions characterized by disc displacement presented with anterior disc displacement, while 27·3% had anterolateral and 25·3% anteromedial disc displacement. Analysis of the data revealed the presence of TMJ pain to be associated with significantly more MR imaging diagnoses of disc displacement without reduction than disc displacement with reduction (P < 0·05), while there was no significant difference in the prevalences of ID and those of absence of ID (P > 0·05). Using chi‐square analysis, no significant relationship was found between the presence of TMJ pain and the MR imaging diagnosis of TMJ ID (P=0·93). Use of the κ statistical test indicated poor diagnostic agreement between the presence of TMJ pain and the MR imaging diagnosis of ID (κ=0·01). The results suggest TMJs with a clinical diagnosis of `absence of TMD' to be associated with a high rate of IDs, while in these instances the clinical variable of TMJ pain may have no effect on prevalences of MR imaging diagnoses TMJ ID. The data confirm the aspect of clinical diagnostic criteria as an unreliable instrument in predicting MR imaging diagnoses of TMJ ID.
– Laser Doppler flowmetry (LDF) is a non‐invasive method to assess pulpal blood flow (PBF). Dental injury has been associated with significant PBF reduction. The purpose of this study was (i) to ...describe PBF characteristics of teeth with specific clinical outcomes, and (ii) to demonstrate diagnostic characteristics for different threshold PBF values for detection of specific multiple adverse outcomes. In 80 trauma patients, a single maxillary incisor treated by repositioning and splinting, and the respective contralateral homologous control tooth were investigated by LDF to assess local PBF values. Perfusion units (PU) were taken in two sessions, on the day of splint removal (session I), and 12 weeks after splint removal (session II). The ability of session II‐related PBF measurements at 2.9, 6.4 and 9.9 PU levels to identify adverse outcomes occurring 36 weeks after splint removal was investigated. Adverse outcomes were classified as type I (loss of sensitivity), type II (periapical radiolucency), type III (grey discolouration), type IV (loss of sensitivity and periapical radiolucency), and type V (loss of sensitivity, periapical radiolucency and grey discolouration of crown). Receiver–operator characteristic (ROC) curves were used to evaluate the sensitivity and specificity of PBF assessments. There was a significant increase in PBF values from session I to session II (P = 0.0001) for teeth without an adverse outcome, while teeth affected by a type II–V outcome showed a significant decrease in PBF values (P < 0.05). PBF measurements did not change over time for the contralateral incisors (P > 0.05). A type IV and V outcome occurred in 21 and 24% of the instances, respectively. The PBF of 2.9 PU demonstrated a sensitivity of 70% and a specificity of 93% for type V outcomes. The best likelihood ratio was found for the PBF 2.9 PU level and incisors associated with a type V outcome. The data suggest that the LDF test to be a valuable diagnostic adjunct for luxated teeth showing signs of adverse outcomes including grey discolouration or a combination of other signs. However, it may also become necessary to apply clinical decision‐making methods in order to correctly evaluate the value of information gathered. The clinical implication is that LDF may become useful in the prediction of adverse outcomes at a much earlier time period than may be accomplished by standard sensitivity tests.
summary Laser Doppler flowmetry (LDF) is a non‐invasive method to assess pulpal blood‐flow (PBF). Dental luxation injuries have been associated with significant PBF reduction. The purpose of this ...study was to describe diagnostic characteristics for different session‐related threshold PBF values for detection of specific adverse outcomes. In 61 trauma patients, a single maxillary incisor treated by repositioning and splinting, and the respective contralateral homologous control tooth were investigated by LDF to assess local PBF values. Perfusion units (PU) were taken 12 weeks (session I) and 24 weeks (session II) after splint removal. The ability of session I‐related PBF measurements at 2·8, 6·4 and 10·1 PU levels, and of session II‐related ameasurements at 2·4, 6·3 and 10·2 PU levels to identify adverse outcomes occurring 36 weeks after splint removal was investigated. Adverse outcomes were classified as type I (periapical radiolucency), type II (grey discoloration), and type III (periapical radiolucency and grey discoloration of crown). Receiver operator characteristic curves were used to evaluate the sensitivity and specificity of PBF assessments. There was no significant difference in PBF values between session I and session II (P > 0·05) for teeth without an adverse outcome, and those with a type I, II or III outcome (P > 0·05). The PBF measurements did not change over time for the contralateral incisors (P > 0·05). A type I, II and III outcome occurred in 36, 21 and 12% of the incisors, respectively. The best likelihood ratio was found for the PBF 6·4 PU level at session I and incisors associated with a type I (20·8) and type II outcome (15·2). The PBV of 6·4 PU demonstrated a sensitivity of 96% and a specificity of 59% for type I outcomes, and a sensitivity of 100% and a specificity of 50% for type II outcomes. The data suggest the LDF test to be a valuable diagnostic adjunct for luxated teeth showing signs of adverse outcomes.
summary Laser Doppler flowmetry (LDF) is a non‐invasive method to assess pulpal blood‐flow (PBF). Dental injury has been associated with significant PBF reduction. The purpose of this study was to ...assess whether (i) the type of luxation trauma may affect PBF measurements and (ii) whether luxation type‐related measurements may show short‐ and long‐term changes of PBF values. In 41 trauma patients, 69 maxillary incisor treated by repositioning and splinting, and the respective contralateral homologous tooth were investigated by LDF to assess local PBF values. Perfusion units were recorded in four sessions, on the day of splint removal, and 12, 24 and 36 weeks after splint removal. Statistical analysis consisted of univariate analysis of variance for repeated measurements. For the LDF measurements, the main effect of the variable ‘session’ was not significant (P = 0·119). However, there was a significant ‘session’/‘luxation type’ interaction (P = 0·000). Analysis of simple session‐within‐luxation type effects revealed intrusive luxations to be associated with a significant decrease in PBF values (P = 0·000), while subluxations (P = 0·568), lateral luxations (P = 0·980), extrusive luxations (P = 0·910), and avulsions (P = 0·996) showed no significant difference between session‐related values. The PBF measurements did not change over time for the contralateral incisors (P = 0·996). The LDF may become useful in the detection of pulpal ischaemic episodes in luxated maxillary incisors after repositioning and splinting. Further studies are warranted to assess the validity of the diagnosis of post‐traumatic ‘ischaemic episodes’ by comparing it with histological tooth pulp changes, and by determining how well it may predict course and response to treatments in clinical trials.
At moderate cell shrinkage, activation of Na(+) channels is the most prominent mechanism of regulatory cell volume increase in rat hepatocytes. The amiloride sensitivity of these channels suggests a ...relation to the family of epithelial Na(+) channels (ENaCs). The present study was performed to determine the pharmacological profile of shrinkage-activated Na(+) channels and to test for ENaC expression in primary cultures of rat hepatocytes; in addition, the influence of the cell volume regulated serine/threonine kinase hSGK on activity and pharmacological profile of rENaC was examined in Xenopus oocytes. Conventional electrophysiology in hepatocytes reveals that the shrinkage-activated Na(+) channel is inhibited by amiloride and EIPA with IC(50) values of 6.0 and 0.12 micromol/l, respectively. Western blots and RT-PCR demonstrate that rat hepatocytes do express all three subunits (alpha, beta, gamma) of ENaC. Coexpression of hSGK with rENaC in Xenopus oocytes reveals that the kinase stimulates ENaC by a factor of 4. Moreover, hSGK decreases the affinity to amiloride (increase of IC(50) from 0.12 to 0.26 micromol/l) and increases the affinity to EIPA (decrease of IC(50) from 250 to 50 micromol/l). In conclusion, rat hepatocytes express ENaC, which is activated by the cell volume-sensitive kinase hSGK. ENaC may contribute to the Na(+) channels activated by osmotic cell shrinkage in hepatocytes, whereby the relatively low amiloride and high EIPA sensitivity of the channel could at least be partially due to modification by SGK, which decreases the amiloride and increases the EIPA sensitivity of ENaC.
Mercury was previously shown to exert toxic effects by influencing ion channels and transporters in the kidney and brain. Gallium alloys were suggested as less toxic restorative materials. To compare ...the toxicity of gallium ions with those of mercury ions, we applied gallium nitrate Ga(NO3)3 (0.1-100 μM and mercuric chloride (HgCl2) (0.001-10 μM) to Xenopus oocytes expressing mammalian ion channels and transport proteins. Mercury (10 μM) inhibited the K+-channels ROMK and HERG, the phosphate transporter NaPi-3, the amino acid transporter rBAT, the cation transporter OCT-2, and the osmolyte transporter BGT. It activated the IKschannel but did not affect the Na+-channel ENaC, the anion channel NaPi-1, and the glucose transporter SGLT-1. Gallium was without significant effect on the channels and on SGLT1, NaPi-3, and rBAT, but inhibited BGT and OCT-2. In conclusion, both Hg2+ and Ga3+ may exert toxic effects on transport systems, which may partially explain their cytotoxic effects.
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