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Metabolism of short-chain fatty acids (SCFA) in the brain, particularly that of acetate, appears to occur mainly in astrocytes. The differential use has been attributed to transport, but the extent to which transmembrane movement of SCFA is mediated by transporters has not been investigated systematically. Here we tested the possible contribution of monocarboxylate transporters to SCFA uptake by measuring fluxes with labelled compounds and by following changes of the intracellular pH in Xenopus laevis oocytes expressing the isoforms MCT1, MCT2 or MCT4. All isoforms mediated significant transport of acetate. Formate, however, was transported only by MCT1. The contribution of MCT1 to SCFA transport was determined by using phloretin as a high-affinity inhibitor, which allowed a paired comparison of oocytes with and without active MCT1.

Laser Doppler flowmetry (LDF) is a non-invasive method to assess pulpal blood flow (PBF). Dental fracture injuries have been associated with significant PBF reduction The purpose of this study was: (i) to evaluate whether the severity of outcomes of dental fracture injuries may be related to LDF measurements of PBF, and (ii) to investigate whether outcomes of dental fracture injuries may predict PBF levels. The relationship between outcomes and PBF measurements was analyzed in 72 permanent maxillary incisors of 52 consecutive dental trauma patients. The diagnostic outcome group comprised 72 incisors with a type I (absence of sensitivity, periapical radiolucency, and grey discoloration of crown) (n = 42), type II (loss of sensitivity) (n = 16), or type III (loss of sensitivity, periapical radiolucency, and/or grey discoloration of crown) diagnosis. 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 diagnostic outcomes. A logistic regression analysis was used to compute the odds ratios for the outcome features for incisor non-injury controls vs two outcome groups: type II (n = 16) and type III (n = 14). PBF measurements that were significantly associated with more severe outcome were PBF levels of

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 < or =3 perfusion units (PU; 170.72 odds ratio; P = 0.000), and those of >3 PU and < or =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.

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 < or =3 perfusion units (PU) (OR 399.4) (P = 0.000), those of >3 PU and < or =6 PU (OR 100.5) (P = 0.000), and those of >6 PU and < or =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.

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.

Objective: Splinting of traumatically displaced or avulsed permanent teeth has been described as an effective modality in the treatment of patients with dental injuries. The purpose of this study was to investigate whether laser Doppler flowmetry (LDF) measurements of pulpal blood flow (PBF) and/or dental injury type may predict treatment outcome of splinting of permanent maxillary incisors., Study Design: The study comprised 64 patients undergoing dental trauma splinting, who were characterized by the presence of a single permanent maxillary incisor affected by a subluxation, luxation, or avulsion type injury. Perfusion units (PU) were taken in 2 sessions, on the day of splint removal (6 weeks after trauma; session I) and 12 weeks after splint removal (session II). At each session, when an injured permanent maxillary central incisor was recorded, the respective contralateral homologous tooth was used as a control. An adverse outcome occurring 36 weeks after splint removal was defined as the presence of "periapical radiolucency and/or grey discoloration." A multiple logistic regression analysis was used to compute the odds ratio for session-related PBF characteristics and dental injury type for adverse outcome (n=22) versus nonadverse outcome (n=42)., Results: There was a significant increase in PBF values from session I to session II (P=.047) for teeth without an adverse outcome, whereas teeth affected by an adverse outcome showed a significant decrease in PBF values (P=.001). PBF measurements did not change over time for the control group of contralateral incisors (P=.185). For the outcome criterion of "presence of periapical radiolucency and/or grey discoloration," there was a significant association between the treatment outcome groups and the variables of dental injury type (P=.049), session-related PBF difference (P=.000), and session II-related PBF level (P=.000). Significant increase in risk of an adverse outcome occurred with a session-related PBF difference (PBF(Session I) - PBF(Session II)) of >/=0 PU (8.6 odds ratio) (P=.014), and a session II-related PBF level of

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.

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.

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 (chi(2) =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 PU and

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 kappa statistical test indicated poor diagnostic agreement between the presence of TMJ pain and the MR imaging diagnosis of ID (kappa=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.

Ample pharmacological evidence points to a role of kinases in the regulation of cell volume. Given the limited selectivity of most inhibitors, however, the specific molecules involved have remained largely elusive. The search for cell volume regulated genes in liver HepG2 cells led to the discovery of the human serum- and glucocorticoid-dependent serine/threonine kinase hsgk1. Transcription and expression of hsgk1 is markedly and rapidly upregulated by osmotic and isotonic cell shrinkage. The effect of osmotic cell shrinkage on hsgk1 is mediated by p38 kinase. Further stimuli of hsgk1 transcription include glucocorticoids, aldosterone, TGF-beta1, serum, increase of intracellular Ca2+ and phorbolesters, whereas cAMP downregulates hsgk1 transcription. The hsgk1 protein is expressed in several epithelial tissues including human pancreas, intestine, kidney, and shark rectal gland. Co-expression of hsgk1 with the renal epithelial Na+-channel ENaC or the Na+/K+/2Cl(-)-cotransporter NKCC2 (BSC1) in Xenopus oocytes, accelerates insertion of the transport proteins into the cell membrane and thus, stimulates channel or transport activity. Thus, hsgk1 participates in the regulation of transport by steroids and secretagogues increasing intracellular Ca2+-activity. The stimulation of hsgk1 transcription by TGF-beta1 may further bear pathophysiological relevance.

The SLC26 gene family (solute carrier family 26) comprises five mammalian genes that encode anion transporter-related proteins. In addition to sat-1 and prestin, which were cloned from rat and gerbil, respectively, three human members have been identified and associated with specific genetic diseases (DTD, diastrophic dysplasia; CLD, congenital chloride diarrhea; PDS, Pendred syndrome). In this study we used a homology approach combined with RACE PCR to identify human SLC26A6, the sixth member of this gene family. Northern blot analysis showed the highest SLC26A6 transcript levels in kidney and pancreas. Expression in MDCK cells and in Xenopus oocytes demonstrated trafficking of the SLC26A6 protein to the cell membrane but did not reveal anion transport activity with tracer uptake or intracellular pH measurements. We determined the genomic structure of the SLC26A6 gene and excluded mutations in the 21 coding exons as the cause of DFNB6 and USH2B, which closely map to the SLC26A6 chromosomal locus (3p21)., (Copyright 2001 Academic Press.)

Cystic fibrosis (CF) is characterized by impaired Cl(-) secretion and increased Na(+) reabsorption in several tissues including respiratory epithelium. Many CFTR mutations have been identified over the past years. However, only a poor correlation between the genotype and lung phenotype was found suggesting additional factors influencing the phenotype and course of the disease. The serine/threonine kinase SGK1 has recently been shown to stimulate the activity of the epithelial Na(+) channel ENaC. A variety of stimuli such as aldosterone, cell shrinkage, insulin or TGF-beta1 stimulate transcription and activate the SGK1 kinase. Here we further examined the effects of SGK1 on ENaC and CFTR which have mutual interactions and we analyzed sgk1 mRNA abundance in lung tissue from CF patients. Coexpression of CFTR and h-SGK1 in Xenopus oocytes increased ENaC currents as previously described. In addition CFTR mediated currents were also stimulated. h-SGK1 accelerated the expression of the amiloride sensitive Na(+)- current in Xenopus oocytes paralleled by increased ENaC-protein abundance in the oocyte membrane, an effect which was reversed by a h-SGK1(K127R) mutation lacking the ATP-binding site. The cation selectivity or Na(+) affinity were not affected. However, coexpression of h-SGK1 with ENaC altered the sensitivity of the Na(+)-channel to the inhibitors amiloride and triamterene. The inhibitory effect of CFTR expression on ENaC current was not affected by coexpression of h-SGK1 in Xenopus oocytes. Lung tissue from CF patients strongly expressed the serine/threonine kinase h-sgk1 which was not the case for non-CF lung tissue. Loss of CFTR function itself in a CF lung epithelial cell line did not increase SGK1 expression. In summary, enhanced expression of h-SGK1 in epithelial cells of CF-lung tissue may be a novel pathophysiological factor contributing to increased Na(+) channel activity and thus to increased Na(+) transport in CF., (Copyright 2001 S. Karger AG, Basel.)

L-Carnitine is essential for the translocation of acyl-carnitine into the mitochondria for beta-oxidation of long-chain fatty acids. It is taken up into the cells by the recently cloned Na(+)-driven carnitine organic cation transporter OCTN2. Here we expressed hOCTN2 in Xenopus laevis oocytes and investigated with two-electrode voltage- clamp and flux measurements its functional and pharmacological properties as a Na(+)-carnitine cotransporter. L-carnitine transport was electrogenic. The L-carnitine-induced currents were voltage and Na(+) dependent, with half-maximal currents at 0.3 +/- 0.1 mM Na(+) at -60 mV. Furthermore, L-carnitine-induced currents were pH dependent, decreasing with acidification. In contrast to other members of the organic cation transporter family, hOCTN2 functions as a Na(+)-coupled carnitine transporter. Carnitine transport was stereoselective, with an apparent Michaelis-Menten constant (K(m)) of 4.8 +/- 0.3 microM for L-carnitine and 98.3 +/- 38.0 microM for D-carnitine. The substrate specificity of hOCTN2 differs from rOCT-1 and hOCT-2 as hOCTN2 showed only small currents with classic OCT substrates such as choline or tetraethylammonium; by contrast hOCTN2 mediated transport of betaine. hOCTN2 was inhibited by several drugs known to induce secondary carnitine deficiency. Most potent blockers were the antibiotic emetine and the ion channel blockers quinidine and verapamil. The apparent IC(50) for emetine was 4.2 +/- 1.2 microM. The anticonvulsant valproic acid did not induce a significant inhibition of carnitine transport, pointing to a different mode of action. In summary, hOCTN2 mediates electrogenic Na(+)-dependent stereoselective high-affinity transport of L-carnitine and Na(+). hOCTN2 displays transport properties distinct from other members of the OCT family and is directly inhibited by several substances known to induce systemic carnitine deficiency.

Transforming growth factor beta (TGF-beta) has been shown to participate in the pathophysiology of diabetic complications. As shown most recently, TGF-beta 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-beta (2 microgram/liter), phorbol 12,13-didecanoate (1 microM), or the Ca(2+) ionophore ionomycin (1 microM) and blunted by high concentrations of nifedipine (10 and 100 microM). 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 microM) and chelerythrine (1 microM) 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.

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., (Copyright 2000 S. Karger AG, Basel.)

The incline and length of guiding elements, i.e. marginal ridges and lingual surfaces of front teeth, marginal ridges and internal cusp slopes of premolars and molars, play an important role in dentistry. Since the so far reported values differ considerably, it was the purpose of the present investigation to replicate the measurements, including all the occlusal landmarks proposed and defined by previous investigators. The measurements were performed on 34 pairs of mounted casts from a selected group of untreated, naturally grown dentitions from adolescents of mean age 14 years. The upper casts were mounted with a face bow, the kinematic hinge axis and the left incisura infraorbitalis representing the posterior and anterior reference points. The lower pinned casts were mounted joint related. All measurements were carried out with a computer-aided, three-dimensional digitizer. The inclines were expressed as angles related to the axis-orbital-plane. Taking the proposed occlusal landmarks as a basis, the inclines of guiding elements were found to be in agreement with previously reported values, despite ethnic and racial differences of the various study-populations. The values, however, differed markedly when measurements based on individual, functional relevant landmarks were compared to measurements based on anatomical, easy identifiable or mathematically constructed landmarks. The successive decrease of the inclines of the guiding elements from the central incisors to the second molars could be confirmed, the molars displaying very flat inclines. Interestingly, 9% of the first molars and 21% of the second molars showed negative values, pointing to a functional arrangement characterized by a buccally oriented occlusal surface of those teeth. Combined with the finding that the length of the guiding elements of the anterior teeth was almost twice as long as that of the posterior teeth, the results corroborate the occlusal concept of an anterior-posterior sequence of the guiding elements, or a so-called sequential guidance with front-canine-dominance.

The present in-vitro study was designed to investigate the chemical efficacy of N-monochloro-D,L,-2-aminobutyrate (NMAB, GK 101E) in removing carious material under clinically relevant conditions, using objective methods of measurement. Assuming that the chemical effectiveness of water in caries removal is minimal, a comparison of the efficacy of GK-101E with that of water was made. The force required to achieve complete caries removal from symmetrically separated carious lesions was determined with the Caridex system, modified by a force gauge. One lesion half was treated with GK-101E, while the corresponding half was treated with water. Thus a difference in the chemical potential of the fluids in softening carious material should lead to a difference in the force required to remove equal quantities of caries. Statistical analysis of the findings of the present study revealed no significant difference between GK-101E and water, with regard to both the force and the number of excavation strokes and the time needed for caries removal. It is concluded that, under the given test conditions, the removal of carious dentine is not significantly enhanced by the chemical action of GK-101E.