bluuebunny/crossref_metadata_2025 huggingface dataset:
Block of voltage‐operated sodium channels by 2,6‐dimethylphenol, a structural analogue of lidocaine's aromatic tail
Authors: Haeseler Gertrud , Bufler Johannes , Merken Sarah , Dengler Reinhard , Aronson Jeffrey , Leuwer Martin
Published: September 2002

The structural features that determine the state‐dependent interaction of local anaesthetics with voltage‐operated sodium channels are still a matter of debate. We have studied the blockade of sodium channels by 2,6‐dimethylphenol, a phenol derivative which resembles the aromatic tail of lidocaine, etidocaine, and bupivacaine.

The effects of 2,6‐dimethylphenol were studied on heterologously (HEK 293) expressed rat neuronal (rat brain IIA) and human skeletal muscle (hSkM1) sodium channels using whole‐cell voltage‐clamp experiments.

2,6‐Dimethylphenol was effective in blocking whole‐cell sodium inward currents. Its potency was comparable to the potency of lidocaine previously obtained with similar protocols by others. The IC50 at −70 mV holding potential was 150 and 187 μM for the skeletal muscle and the neuronal isoform, respectively. In both isoforms, the blocking potency increased with the fraction of inactivated channels at depolarized holding potentials. However, the block achieved at −70 mV with respect to −150 mV holding potential was significantly higher only in the skeletal muscle isoform. The estimated dissociation constant Kd from the inactivated state was 25 μM and 28 μM in the skeletal muscle and the neuronal isoform, respectively. The kinetics of drug equilibration between resting and inactivated channel states were about 10 fold faster compared with lidocaine.

Our results show that the blockade induced by 2,6‐dimethylphenol retains voltage‐dependency, a typical feature of lidocaine‐like local anaesthetics. This is consistent with the hypothesis that the ‘aromatic tail’ determines the state‐dependent interaction of local anaesthetics with the sodium channel.

British Journal of Pharmacology (2002) 137, 285–293. doi:10.1038/sj.bjp.0704854
Gene expressions in Jurkat cells poisoned by a sulphur mustard vesicant and the induction of apoptosis
Authors: Zhang Peng , Ng Patrick , Caridha Diana , Leach Richard A , Asher Ludmila V , Novak Mark J , Smith William J , Zeichner Steven L , Chiang Peter K
Published: September 2002

The sulphur mustard vesicant 2‐chloroethylethyl sulphide (CEES) induced apoptosis in Jurkat cells.

Akt (PKB), a pivotal protein kinase which can block apoptosis and promotes cell survival, was identified to be chiefly down‐regulated in a dose‐dependent manner following CEES treatment. Functional analysis showed that the attendant Akt activity was simultaneously reduced.

PDK1, an upstream effector of Akt, was also down‐regulated following CEES exposure, but two other upstream effectors of Akt, PI3‐K and PDK2, remained unchanged.

The phosphorylation of Akt at Ser473 and Thr308 was significantly decreased following CEES treatment, reflecting the suppressed kinase activity of both PDK1 and PDK2.

Concurrently, the anti‐apoptotic genes, Bcl family, were down‐regulated, in sharp contrast to the striking up‐regulation of some death executioner genes, caspase 3, 6, and 8.

Based on these findings, a model of CEES‐induced apoptosis was established. These results suggest that CEES attacked the Akt pathway, directly or indirectly, by inhibiting Akt transcription, translation, and post‐translation modification.

Taken together, upon exposure to CEES, apoptosis was induced in Jurkat cells via the down‐regulation of the survival factors that normally prevent the activation of the death executioner genes, the caspases.

British Journal of Pharmacology (2002) 137, 245–252. doi:10.1038/sj.bjp.0704856
The smooth muscle relaxant effect of hydrogen sulphide in vitro: evidence for a physiological role to control intestinal contractility
Authors: Teague B , Asiedu S , Moore P K
Published: September 2002

Sodium hydrogen sulphide (NaHS), a donor of hydrogen sulphide (H2S), produced dose‐related relaxation of the rabbit isolated ileum (EC50, 76.4±7.9 μM) and rat vas deferens (EC50, 64.8±5.4 μM) and reduced ACh‐mediated contraction of the guinea‐pig isolated ileum.

NaHS also reduced the response of the guinea‐pig (EC50, 80.0±5.7 μM) and rat (EC50, 108.2±11.2 μM) ileum preparations to electrical stimulation of the intramural nerves. In guinea‐pig ileum this effect was spontaneously reversible and mimicked by sodium nitroprusside (SNP, EC50, 2.1 μM). Combination of NaHS (20 μM) with SNP (0.5 μM) produced a greater than additive inhibition of the twitch response of the ileum to electrical stimulation.

The inhibitory effect of NaHS on the field‐stimulated guinea‐pig ileum was unaffected by pretreatment with L‐NAME (100 μM), indomethacin (10 μM), naloxone (1 μM) or glibenclamide (100 μM). Furthermore, NaHS (200 μM) did not affect the contractile response of the ileum to KCl (10 to 60 mM).

Propargylglycine (PAG, 1 mM) and β‐cyanoalanine (BCA, 1 mM) (inhibitors of cystathionine‐γ‐lyase) but not aminooxyacetic acid (AOAA, 1 mM) (inhibitor of cystathionine‐β‐synthetase) caused a slowly developing increase in the contraction of the guinea‐pig ileum to field stimulation. This effect was reversed by cysteine (1 mM).

These results show that NaHS relaxes gastrointestinal and urogenital smooth muscle and suggest that H2S is responsible for these effects. The possibility that endogenous H2S, formed as a consequence of activation of intramural nerves, plays a part in controlling the contractility of the guinea‐pig ileum is discussed.

British Journal of Pharmacology (2002) 137, 139–145. doi:10.1038/sj.bjp.0704858
Bertosamil blocks HERG potassium channels in their open and inactivated states
Authors: Zitron Edgar , Karle Christoph A , Wendt‐Nordahl Gunnar , Kathöfer Sven , Zhang Wei , Thomas Dierk , Weretka Slawomir , Kiehn Johann
Published: September 2002

Bertosamil is chemically related to the class‐III anti‐arrhythmic drug tedisamil and has been developed as a bradycardic, anti‐ischemic and anti‐arrhythmic drug. Its anti‐arrhythmic properties might in part be attributed to its block of voltage‐dependent potassium channels Kv1.2, Kv1.4. and Kv1.5. However, HERG‐potassium channel block as an important target for class‐III drugs has not yet been investigated.

We investigated the effect of bertosamil on the HERG potassium channel heterologously expressed in Xenopus oocytes with the two‐electrode voltage‐clamp technique.

Bertosamil (70 μM) inhibited HERG tail currrent after a test pulse to 30 mV by 49.3±8.4% (n=5) and the IC50 was 62.7 μM. Onset of block was fast, i.e. 90% of inhibition developed within 180±8.22 s (n=5), and block was totally reversible upon washout within 294±38.7 s (n=5).

Bertosamil‐induced block of HERG potassium channels was state‐dependent with block mainly to open‐ and inactivated channels. Half‐maximal activation voltage was slightly shifted towards more negative potentials.

Steady‐state inactivation of HERG was not influenced by bertosamil. Bertosamil block elicited voltage–but no frequency‐dependent effects.

In summary, bertosamil blocked the HERG potassium channel. These blocking properties may contribute to the anti‐arrhythmic effects of bertosamil in the treatment of atrial and particular ventricular arrhythmias.

British Journal of Pharmacology (2002) 137, 221–228. doi:10.1038/sj.bjp.0704859
Blocking action of chromanol 293B on the slow component of delayed rectifier K+ current in guinea‐pig sino‐atrial node cells
Authors: Ding Wei‐Guang , Toyoda Futoshi , Matsuura Hiroshi
Published: September 2002

In guinea‐pig sino‐atrial (SA) node cells the delayed rectifier K+ current (IK) is composed of rapidly and slowly activating components of IK (IKr and IKs, respectively). The present study was undertaken to characterize the blocking action of the chromanol derivative 293B on IKs in guinea‐pig SA node cells using whole‐cell patch‐clamp technique.

Bath application of 293B blocked IKs, elicited by 4‐s depolarizing voltage pulses from a holding potential of −50 mV, under conditions in which the L‐type Ca2+ current (ICa,L) and IKr were inhibited; the effect was concentration‐dependent with an IC50 of 5.3 μM, when evaluated by the decrease in the amplitude of IKs tail current following 4‐s depolarizing voltage steps to +50 mV.

The 293B block of IKs progressed with time during depolarizing voltage steps with a more rapid block at higher concentrations.

The block of IKs by 293B was fully reversed within a few minutes after washing off the drug, even when a maximal effect (a nearly full block) was achieved at high drug concentration (50 μM).

Bath application of 293B at 50 μM greatly and reversibly reduced the amplitude of IKs which is maximally stimulated by β‐adrenergic agonist isoprenaline (1 μM), while the degree of 293B block of the isoprenaline‐stimulated IKs was slightly but significantly smaller than that of non‐stimulated IKs (94.0±0.98% block, n=6 vs 99.4±0.45% block, n=6; P<0.01).

We conclude that, in guinea‐pig SA node cells (i) 293B is a potent and fully reversible blocker of IKs in control and during β‐adrenergic stimulation and (ii) block with 293B occurs in a time‐dependent manner during depolarizing voltage steps.

British Journal of Pharmacology (2002) 137, 253–262. doi:10.1038/sj.bjp.0704861
Bradykinin potentiation by ACE inhibitors: a matter of metabolism
Authors: Tom Beril , Dendorfer Andreas , Vries René de , Saxena Pramod R , Jan Danser A H
Published: September 2002

Studies in isolated cells overexpressing ACE and bradykinin type 2 (B2) receptors suggest that ACE inhibitors potentiate bradykinin by inhibiting B2 receptor desensitization, via a mechanism involving protein kinase C (PKC) and phosphatases. Here we investigated, in intact porcine coronary arteries, endothelial ACE/B2 receptor ‘crosstalk’ as well as bradykinin potentiation through neutral endopeptidase (NEP) inhibition.

NEP inhibition with phosphoramidon did not affect the bradykinin concentration‐response curve (CRC), nor did combined NEP/ACE inhibition with omapatrilat exert a further leftward shift on top of the ≈10 fold leftward shift of the bradykinin CRC observed with ACE inhibition alone.

In arteries that, following repeated exposure to 0.1 μM bradykinin, no longer responded to bradykinin (‘desensitized’ arteries), the ACE inhibitors quinaprilat and angiotensin‐(1‐7) both induced complete relaxation, without affecting the organ bath fluid levels of bradykinin. This phenomenon was unaffected by inhibition of PKC or phosphatases (with calphostin C and okadaic acid, respectively).

When using bradykinin analogues that were either completely or largely ACE‐resistant ([Phe8Ψ(CH2‐NH)Arg9]‐bradykinin and [ΔPhe5]‐bradykinin, respectively), the ACE inhibitor‐induced shift of the bradykinin CRC was absent, and its ability to reverse desensitization was absent or significantly reduced, respectively. Caveolar disruption with filipin did not affect the quinaprilat‐induced effects. Filipin did however reduce the bradykinin‐induced relaxation by ≈25–30%, thereby confirming that B2 receptor‐endothelial NO synthase (eNOS) interaction occurs in caveolae.

In conclusion, in porcine arteries, in contrast to transfected cells, bradykinin potentiation by ACE inhibitors is a metabolic process, that can only be explained on the basis of ACE‐B2 receptor co‐localization on the endothelial cell membrane. NEP does not appear to affect the bradykinin levels in close proximity to B2 receptors, and the ACE inhibitor‐induced bradykinin potentiation precedes B2 receptor coupling to eNOS in caveolae.

British Journal of Pharmacology (2002) 137, 276–284. doi:10.1038/sj.bjp.0704862
Induction of insulin resistance by high‐sucrose feeding does not raise mean arterial blood pressure but impairs haemodynamic responses to insulin in rats
Authors: Santuré Marta , Pitre Maryse , Marette André , Deshaies Yves , Lemieux Christian , Lariviére Richard , Nadeau André , Bachelard Hélène
Published: September 2002

This study was undertaken to further investigate the effects of a sucrose‐enriched diet on vascular function and insulin sensitivity in rats.

Male Sprague‐Dawley rats were randomized to receive a sucrose‐ or regular rat chow‐diet for 4 weeks. A first group of sucrose‐ and chow‐fed rats was instrumented with pulsed Doppler flow probes and intravascular catheters to determine blood pressure, heart rate, regional blood flows and insulin sensitivity in conscious rats. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Glucose transport activity was examined in isolated muscles by using the glucose analogue [3H]‐2‐deoxy‐D‐glucose. A second group of sucrose‐ and chow‐fed rats was used to obtain information regarding nitric oxide synthase (NOS) isozymes protein expression in muscles, and determine endothelin content in vascular tissues isolated from both dietary groups.

Sucrose feeding was found to induce insulin resistance, but had no effect on resting blood pressure, heart rate, or regional haemodynamics. This insulin resistance was accompanied by alteration in the vascular responses to insulin. Insulin‐mediated skeletal muscle vasodilation was impaired, whereas the mesenteric vasoconstrictor response was potentiated in sucrose‐fed rats. A reduction in eNOS protein content in muscle and an increase in vascular endothelin peptide were noted in these animals. Moreover, a reduction in insulin‐simulated glucose transport activity was also noted in muscles isolated from sucrose‐fed rats.

Together these data suggest that a cluster of metabolic and haemodynamic abnormalities occur in response to the intake of simple sugars in rats.

British Journal of Pharmacology (2002) 137, 185–196. doi:10.1038/sj.bjp.0704864
Production of inflammatory mediators by renal epithelial cells is insensitive to glucocorticoids
Authors: Haij Simone de , Woltman Andrea M , Bakker Astrid C , Daha Mohamed R , van Kooten Cees
Published: September 2002

In the present study we investigated the effect of glucocorticoids on the activation of renal tubular epithelial cells, which are thought to play an important role in inflammatory processes in the kidney.

Activation of renal epithelial cells by IL‐1, TNF‐α or CD40L resulted in increased production of cytokines and chemokines. Both in the renal epithelial cell line HK‐2 and in primary cultures of human proximal tubular epithelial cells (PTEC) production of IL‐6, IL‐8 and monocyte chemotactic protein 1 (MCP‐1) was not inhibited by glucocorticoids, independent of the stimulus.

In contrast, dexamethasone strongly inhibited cytokine production by immortalized renal fibroblasts and an airway epithelial cell line (A549).

Stimulation of renal epithelial cells resulted in activation of NF‐κB, a pivotal transcription factor in the regulation of cytokine genes, as was shown by IκB‐α degradation and increased DNA‐binding activity. In contrast to dexamethasone, addition of the NF‐κB inhibitors pyrrolidine dithiocarbamate (PDTC) and n‐tosyl‐l‐phenylalanine chloromethyl ketone (TPCK) completely abolished cytokine and chemokine production.

Renal epithelial cells express abundant levels of the functional glucocorticoid receptor alpha (GRα) isoform and low levels of the inhibitory beta isoform (GRβ).

In conclusion, cytokine production by renal epithelial cells is insensitive to the inhibitory effects of glucocorticoids. The lack of dexamethasone‐mediated inhibition was specific for renal epithelial cells and could not be explained by an increased expression of the glucocorticoid receptor beta isoform.

British Journal of Pharmacology (2002) 137, 197–204. doi:10.1038/sj.bjp.0704866
Beta 3‐adrenoceptor in rat aorta: molecular and biochemical characterization and signalling pathway
Authors: Rautureau Yohann , Toumaniantz Gilles , Serpillon Sabrina , Jourdon Philippe , Trochu Jean‐Noël , Gauthier Chantal
Published: September 2002

We have previously demonstrated that β3‐adrenoceptor (β3‐AR) stimulation induces endothelium‐dependent vasorelaxation in rat aorta through the activation of an endothelial NO synthase associated with an increase in intracellular cGMP. The aim of the present study was to localise β3‐AR to confirm our functional study and to complete the signalling pathway of β3‐AR in rat aorta.

By RT–PCR, we have detected β3‐AR transcripts both in aorta and in freshly isolated endothelial cells. The absence of markers for adipsin or hormone‐sensitive lipase in endothelial cells excluded the presence of β3‐AR from adipocytes. The localization of β3‐AR in aortic endothelial cells was confirmed by immunohistochemistry using a rat β3‐AR antibody.

To identify the G protein linked to β3‐AR, experiments were performed in rat pre‐treated with PTX (10 μg kg−1), a Gi/0 protein inhibitor. The blockage of Gi/0 protein by PTX was confirmed by the reduction of vasorelaxation induced by UK 14304, a selective α2‐AR agonist. The cumulative concentration‐response curve for SR 58611A, a β3‐AR agonist, was not significantly modified on aorta rings from PTX pre‐treated rats.

At the same level of contraction, the relaxations induced by 10 μM SR 58611A were significantly reduced in 30 mM‐KCl pre‐constricted rings (Emax=16.7±8.4%, n=5), in comparison to phenylephrine (0.3 μM) pre‐constricted rings (Emax=49.11±11.0%, n=5, P<0.05). In addition, iberotoxin (0.1 μM), glibenclamide (1 μM) and 4‐aminopyridine (1 mM), selective potassium channels blockers of KCa, KATP, and Kv respectively, decreased the SR 58611A‐mediated relaxation.

We conclude that β3‐AR is preferentially expressed in rat aortic endothelial cells. β3‐AR‐mediated aortic relaxation is independent of Gi/0 proteins stimulation, but results from the activation of several potassium channels, KCa, KATP, and Kv.

British Journal of Pharmacology (2002) 137, 153–161. doi:10.1038/sj.bjp.0704867
A comparison of digital and film radiography in Dutch dental practices assessed by questionnaire.
Authors: Berkhout W E R , Sanderink G C H , Van der Stelt P F
Published: September 2002

OBJECTIVES

The purpose of this study was to assess the experiences of general dental practitioners (GDPs) with solid-state and storage phosphor digital sensors compared to film.

METHODS

In a mail survey 578 questionnaires were sent to Dutch GDPs who were users of digital X-ray detectors and film. The questionnaire requested demographic data, information about the digital system used and the user-friendliness of the X-ray detector system. In the analysis of the data these variables were related to the type of system used and also to the demographic data. The data were analysed using descriptive statistics, variance-analysis (One-Way ANOVA) and nonparametric tests (Kruskal-Wallis, Mann-Whitney and Wilcoxon) (SPSS 9.0).

RESULTS

Four hundred and twenty-four questionnaires were returned (overall response rate 73%). The user-friendliness of the handling of the different systems before exposing the radiograph is better for conventional film, whereas the handling after exposing the radiograph favoured the digital X-ray detector systems.

CONCLUSIONS

The user-friendliness was best for film pre-exposure and digital sensors post-exposure.
Oral radiographic predictors of osteoporosis.
Authors: White S C
Published: September 2002

Osteoporosis is a systemic skeletal disease characterized by low bone mass and micro architectural deterioration of the bone scaffold that result in increased bone fragility and susceptibility to fracture. It is one of the most common disorders of the elderly and is estimated to effect 75 million people in Europe, Japan and the USA. The purpose of screening for osteoporosis is to identify individuals who are likely to benefit from treatment. The fact that dental radiographs are regularly made on a large fraction of the adult population makes their potential use as a marker of skeletal health an exciting avenue of research. In the last four decades numerous research teams have reported oral radiographic findings associated with osteoporosis. The preponderance of the evidence shows that the jaws of subjects with osteoporosis show reduced bone mass and altered morphology. Clinically useful predictions of individuals most likely to develop osteoporotic fractures will require a multifactorial model including both radiographic and clinical findings. Future efforts should continue to search for oral radiographic signs with high sensitivity and specificity for osteoporosis, identify clinical signs available in the dental office associated with osteoporosis, develop multidisciplinary classification methods including both radiographic and clinical parameters, and automate radiographic and clinical analyses as much as possible to minimize the involvement of the dentist as well as to standardize data collection.
Odontogenic myxomas in the Hong Kong Chinese: clinico-radiological presentation and systematic review.
Authors: MacDonald-Jankowski D S , Yeung R , Lee K M , Li T K L
Published: September 2002

AIM

The aim of this study was to determine the clinical and radiological presentation on plain films of central odontogenic myxomas (OM) in the Hong Kong Chinese and compare them to other reported series by a systematic review (SR).

METHODS

The study had two elements, that of a complete series of all OMs presenting at a major Chinese maxillofacial surgical unit and a SR. The files of the Department of Oral and Maxillofacial Surgery of the University of Hong Kong between 1989 and 2000 were reviewed for OM cases. The relevant literature was identified by electronic databases, review of citation lists and handsearching of key journals. The principal selection criterion was that the study should represent a complete collection of cases.

RESULTS

The SR revealed that only a quarter of the reports provided any quantitative radiological details. Just under half of the included reports provided the relative period prevalence of OMs compared to other odontogenic tumours, but these reports almost completely excluded consideration not only of the radiology but also specific clinical details. Furthermore, they did not report of recurrence data, an important feature of the OM. Most of the most recent reports were concerned with relative period prevalence. The relative period prevalence and 'number of OMs per hospital per year' of studies separated by two or more decades in Hong Kong and Nigeria indicate an increase in the number of lesions diagnosed as OMs. The 10 Hong Kong cases were broadly consistent with the predilections for females and the mandible of other reports. The mean age at first presentation in the present report is 36.9, older than the other reports. Most lesions are large, affecting both posterior and anterior quadrants. They appear to be larger than those in many other reports. Two of the OMs are accompanied by histories of recent rapid growth. Tooth displacement and root resorption are more frequently observed in OMs in the present study. Although all OMs in the present study are still being followed up after surgery, none have recurred.

CONCLUSION

Although the presentation of larger lesions in the older Chinese could in part be explained by attitudes rooted in traditional medicine in spite of the widespread availability of modern medical care in Hong Kong, there is a history of recent rapid growth in at least two cases. An emphasis by recent reports on the OMs' relative period prevalence of concurrent odontogenic lesions, has omitted recording the radiology and the specific clinical details usually required for diagnosis.,
Thin-plate spline (TPS) graphical analysis of the mandible on cephalometric radiographs.
Authors: Chang H P , Liu P H , Chang H F , Chang C H
Published: September 2002

We describe two cases of Class III malocclusion with and without orthodontic treatment. A thin-plate spline (TPS) analysis of lateral cephalometric radiographs was used to visualize transformations of the mandible. The actual sites of mandibular skeletal change are not detectable with conventional cephalometric analysis. These case analyses indicate that specific patterns of mandibular transformation are associated with Class III malocclusion with or without orthopaedic therapy, and visualization of these deformations is feasible using TPS graphical analysis.
Radiographic diagnosis of Limbus vertebra on a lateral cephalometric film: report of a case.
Authors: Mupparapu M , Vuppalapati A , Mozaffari E
Published: September 2002

Although Limbus vertebra is not an uncommon radiological finding in an adult, it is a rare finding in the child or adolescent. The most common site for the presence of Limbus vertebra is the mid-lumbar region and less commonly occurs in the mid cervical region. It is a defect (tiny unfused apophyseal fragment) in the anterior margin of the vertebral body usually at the superior anterior margin in the lumbar vertebrae and at the anteroinferior margin in the cervical vertebrae. These margins are the sites of epiphyseal centers on vertebrae. A case of Limbus vertebra seen on a routine lateral cephalometric radiograph taken prior to Orthodontic treatment is reported and the literature is reviewed. The Limbus vertebra is thought to result from herniation of the nucleus pulposus through the ring apophysis prior to fusion isolating a small segment of the vertebral rim. This could be mistaken for a fracture, infection or tumor resulting in further invasive diagnostic procedures. It is important to recognize that this represents the sequela of a remote injury in an immature skeleton. A sound knowledge of this anomaly is essential for all clinicians so that appropriate measures can be taken without unduly alarming patients.
Accuracy of tuned aperture computed tomography in the diagnosis of radicular fractures in non-restored maxillary anterior teeth--an in vitro study.
Authors: Nair M K , Nair U P , Gröndahl H-G , Webber R L
Published: September 2002

OBJECTIVES

This study compared the accuracy of three radiographic imaging modalities for the detection of artificially induced radicular fractures on maxillary anterior teeth.

METHODS

Fractures were induced in 28 of 54 maxillary incisors in 15 cadaver specimens using a distally directed force. Radiographs evaluated included conventional two-dimensional direct digital radiographs (DDI), unprocessed Tuned Aperture Computed Tomography (TACT-U) and iteratively restored TACT (TACT-IR). Eight observers recorded their findings using a five-point confidence-rating scale. Receiver Operating Characteristic (ROC) analyses were done, followed by ANOVA to test for significant effects of observers, imaging modality and fracture location. Post hoc tests were carried out in instances where ANOVA indicated significance.

RESULTS

The areas under the ROC-curves (A(z)) were, respectively: DDI: 0.53; TACT-U: 0.83 and TACT-IR: 0.97. TACT-IR and TACT-U performed significantly better than DDI (P < 0.001) with TACT-IR providing a higher detection accuracy than TACT-U (P < 0.033). A difference in detection accuracy was also noted based on fracture location (P < 0.001). Tukey's post hoc analyses revealed that fractures extending beyond the middle third of the root were more accurately detected. Inter-observer agreement was 0.68, and intra-examiner agreement, 0.87 (kappa analysis).

CONCLUSIONS

TACT performed significantly better than direct digital images in detecting trauma-induced radicular fractures in unrestored, maxillary anterior teeth.
Utility of frequency-selective fat saturation T2-weighted MR images for the detection of joint effusion in the temporomandibular joint.
Authors: Tanaka T , Morimoto Y , Masumi S , Tominaga K , Ohba T
Published: September 2002

OBJECTIVES

To evaluate joint effusion in the temporomandibular joint (TMJ) using frequency-selective fat saturation (FS) T2-weighted images and assess this technique. To investigate whether bone marrow abnormalities and magnetic resonance imaging (MRI) findings of internal derangement may be linked to joint effusion in the TMJ in patients with pain.

METHODS

TMJ effusion was sought on FS T2-weighted images and conventional T2-weighted images in 400 joints from 200 patients with TMJ-related pain. Self-reported pain records were obtained from patients immediately before MRI and images assessed by the amount of TMJ fluid graded bilaterally using reference films by two radiologists. Other parameters recorded included disk displacement categories and condyle marrow abnormalities. The association between the recorded parameters and TMJ effusion judged by FS-sequences or conventional sequences was analysed using chi-square and Kappa tests.

RESULTS

The detection rate of TMJ effusion by FS-sequences was significantly greater than by conventional methods, and the results showed a significant relationship between MRI interpretation of TMJ effusion using FS-sequences or conventional methods and the presence of pain. The correlation between TMJ effusion on FS-sequences and pain was significantly stronger than the conventional method. Kappa test indicated good agreement between pain and MRI TMJ effusion by FS-sequences (kappa = 0.66), but not by conventional sequences (kappa = 0.56). The other parameters showed a similar trend for TMJ-related pain.

CONCLUSIONS

FS T2-weighted imaging is useful for detection of TMJ effusion, without known causes and confirms the importance of TMJ effusion as an indicator in patients with TMJ-related pain, bone abnormalities, and disk displacement.
A new device for measuring density of jaw bones.
Authors: Yang J , Chiou R , Ruprecht A , Vicario J , MacPhail L A , Rams T E
Published: September 2002

OBJECTIVES

The purpose of this project was to develop a lightweight, simple device to evaluate alveolar process bone density using normal intraoral and extraoral imaging procedures.

METHODS

A simple lightweight device was constructed using barium sulfate as the major radiopaque component. The 5 x 32 x 12 mm(3) resin block has eight segments with known densities ranging from 1.304 (g/cm(3)) to 1.982 (g/cm(3)). The device was integrated into an XCP unit for standard intraoral radiographs and placed between the jaws for computer aided tomographic imaging. The relationship between the device segment densities and the optical densities of the exposed film was plotted.

RESULTS

A linear inverse relationship was found between the device segment densities and optical densities when segment densities were between 1.304 (g/cm(3)) to 1.882 (g/cm(3)). However, the relationship was non-linear for segment densities above 1.882 (g/cm(3)).

CONCLUSIONS

Normal human bone density is 1.85 (g/cm(3)), and this densitometer is useful for determination of material densities from 1.304 (g/cm(3)) to 1.882 (g/cm(3)). The device may be useful for precise bone density assessment.
A sequential approach to radiological interpretation.
Authors: Farman A G , Kushner G M , Gould A R
Published: September 2002

A case of large glandular odontogenic cyst of the mandible is presented in which the panoramic radiograph also demonstrated a soft tissue lesion consistent with carotid aneurysm. CT confirmed the bucco-lingual extent of the mandibular lesion and the presence of a soft tissue lesion consistent with an aneurysm of the internal carotid artery. CT angiography, MR angiography and US were used to rule out a carotid artery aneurysm prior to surgery of the mandibular lesion.
Radiographic practices of dentists undertaking endodontics in New Zealand.
Authors: Chandler N P , Koshy S
Published: September 2002

OBJECTIVES

To determine the radiographic practices of New Zealand dentists undertaking root canal treatment, and to investigate the relationship between radiographic practices and educational and clinical factors.

METHODS

A questionnaire was sent to all 1200 general dental practitioners and five specialist endodontists in New Zealand. Data were subjected to descriptive and analytical statistics.

RESULTS

The response rate was 79%. The mean number of root canal treatments done by general dentists in the previous 12 months was 103, and for the specialists 938. Pre-operative views were taken by 57.1% of respondents all the time and by 34.8% in most cases. The long cone paralleling and bisecting angle techniques were in regular use by similar numbers of respondents, and over one half of the practitioners regularly used film holders and electronic apex locators. Working length films were taken by 67% of practitioners all the time and by 18% in most cases. One-quarter of practitioners took a master point view all the time, and 15% did this for most cases. Almost 65% always took a film of the completed root filling and 21% did for most cases. Twenty-three per cent of practitioners did not follow up their work.

CONCLUSIONS

The majority of respondents used radiographs pre-operatively, for working length assessment and to assess the final root filling. There was a general improvement in radiographic practices compared with data from a previous national survey held in 1980.
Lingual and buccal mandibular bone depressions: a review based on 583 cases from a world-wide literature survey, including 69 new cases from Japan.
Authors: Philipsen H P , Takata T , Reichart P A , Sato S , Suei Y
Published: September 2002

OBJECTIVES

To review present knowledge of so-called lingual and buccal mandibular bone depressions (n = 583) based on studies of 247 contemporary and 267 archaeological cases from a world-wide literature survey in addition to 69 new cases from Japan.

METHODS

The 69 cases from Japan were retrieved through examination of 42,600 consecutive panoramic radiographs.

RESULTS

Bone depressions can be divided into four topographical variants: (1) lingual anterior mandibular body (incisor-canine- premolar area) above the mylohyoid muscle; (2) posterior to the mandibular angle-first permanent molar area, below the mandibular canal, and a third located to the ascending, lingual mandibular ramus, posterior to the lingual foramen, just below the neck of the condyle. An excessively rare fourth variant is located to the buccal aspects of the ascending mandibular ramus.

CONCLUSIONS

The present concept favours that all variants have a common origin: a hyperplastic/hypertrophic lobe (or aberrant lobe) of the sublingual, submandibular or parotid salivary gland, exerting pressure upon the cortex of the mandible by the respective gland, leading to focal atrophy or resorption of the bone. The bone depressions take years to develop, appearing radiographically not until the 5th to 6th decades.
Appearance, location, course, and morphology of the mandibular incisive canal: an assessment on spiral CT scan.
Authors: Jacobs R , Mraiwa N , vanSteenberghe D , Gijbels F , Quirynen M
Published: September 2002

OBJECTIVES

To assess the appearance, location, and course of the incisive canal as compared to other anatomical landmarks on spiral CT of the mandible.

METHODS

Study material included 230 spiral CT scans taken for preoperative planning of implant placement in the posterior mandible. All scanning was performed using a standard exposure and patient positioning protocol. Axial, panoramic, and reformatted cross-sectional images were carefully examined. Visibility of the incisive canal and other anatomical landmarks was scored using a four-point rating scale. The vertical and buccolingual diameter of the outer contour as well the diameter of the inner contour of the incisive canal were measured using a digital sliding caliper.

RESULTS

An incisive canal was identified in 93% of the cases, with good visibility in 22% of the cases. Mean (s.d.) vertical diameter, buccolingual diameter, and inner diameter of the incisive canal were 4.7 (1.1), 3.7 (0.7), and 1.1 (0.3) mm respectively. The mandibular canal, mental foramen, lingual foramen, and anterior looping appeared in 98, 100, 82 and 7% of the images respectively.

CONCLUSIONS

A well-defined incisive canal could be detected in the majority of spiral CT scans. Its radiographic detection remained lower than for the mandibular canal or mental foramen, but higher than for the visibility of the lingual foramen. Visualisation of the incisive canal and the occasional presence of an anterior looping, demonstrates the potential value of cross-sectional imaging of the anterior mandible for presurgical planning purposes.
Application of Physiological Genomics to the Microcirculation
Authors: Greene Andrew S.
Published: September 2002

Physiological genomics represents a new challenge in the biological sciences–the quest to define the functions of thousands of genes that will emerge from the sequencing of the human genome and the genomes of other model organisms. Because the attention of the scientific community has focused on this task, new tools that will allow high‐efficiency identification of gene function are being developed at remarkable speed. Physiological genomic approaches to understanding integrated systems function are now becoming widely used in many areas of biological research. The availability of genomic information across species has now revealed a striking degree of conservation of both gene order and function, allowing researchers to easily move from model organisms to man in the hunt for gene function. Physiological genomics approaches in the cardiovascular system have focused on disease‐based models and the behavior of large vessels. In the microcirculation, genomic studies have largely been confined to the use of single gene knockouts or to the study of angiogenesis. This review summarizes the strategies for physiological genomics that are appropriate to the study of the microcirculation and discusses several key discoveries that have been made by using these approaches.
DNA Microarrays: Their Use and Misuse
Authors: Li Xinmin , Gu Weikuan , Mohan Subburaman , Baylink David J.
Published: September 2002

DNA microarray represents one of the major advances in functional genomics. Its ability to study expression of several thousands of genes or even all genes in the entire genome in a single experiment has changed the way in which we address basic biomedical questions. Numerous publications have shown its utility in drug discovery, disease diagnosis, novel gene identification, and understanding complex biological systems. However, there are substantive technical issues associated with the use of this technology that limit the interpretation of microarray data. In this review, we first give an overview of DNA microarray technology and then focus on uncertainty areas of microarray technology that include making microarrays, isolation of RNA and labeling, hybridization and scanning, and data analysis. The center theme of this review is to improve microarray reproducibility by addressing common technical problems. Finally, we briefly summarize microarray's applications in biomedical research.
Virally Mediated Gene Transfer to the Vasculature
Authors: Gunnett Carol A. , Heistad Donald D.
Published: September 2002

Gene transfer technology provides valuable tools for the study of vascular biology. By using gene transfer, effects of specific gene products can be evaluated in a highly selective manner. In recent years, techniques used for gene transfer have been adapted for applications to blood vessels, including microvessels, both in vitro and in vivo. The purpose of this review is to provide a survey of published work in this field of investigation and to discuss advantages and limitations of current methods used for gene transfer to the vasculature.
Nonviral Gene Transfer Strategies for the Vasculature
Authors: Young Jennifer L. , Dean David A.
Published: September 2002

Major attention has been focused on the development of gene therapy approaches for the treatment of vascular diseases. In this review, we focus on an alternative use of gene therapy: the use of genetic means to study vascular cell biology and physiology. Both viral and nonviral gene transfer strategies have limitations, but because of the overwhelming inflammatory responses associated with the use of viral vectors, nonviral gene transfer methods are likely to be used more abundantly for future applications in the vasculature. Researchers have made great strides in the advancement of gene delivery to the vasculature in vivo. However, the efficiency of gene transfer seen with most nonviral approaches has been exceedingly low. We discuss how to circumvent and take advantage of a number of the barriers that limit efficient gene delivery to the vasculature to achieve high‐level gene expression in appropriate cell types within the vessel wall. With such levels of expression, gene transfer offers the ability to alter pathways at the molecular level by genetically modulating the activity of a gene product, thus obviating the need to rely on pharmacological agents and their foreseen and unforeseen side effects. This genetic ability to alter distinct gene products within a signaling or biosynthetic pathway or to alter structural interactions within and between cells is extremely useful and technologically possible today. Hopefully, with the availability of these tools, new advances in cardiovascular physiology will emerge.
Use of Antisense Oligonucleotides: Advantages, Controls, and Cardiovascular Tissue
Authors: Golden Teresa , Dean Nicholas M. , Honkanen Richard E.
Published: September 2002

Antisense oligonucleotides are short pieces of synthetic, chemically modified DNA or RNA that are designed to interact by Watson‐Crick base pairing with mRNA encoding a targeted protein. During the past 20 years the technology associated with the development of antisense has improved dramatically, and emerging chemistries have made antisense oligonucleotides into powerful and versatile tools to study the function of proteins in living cells. The dramatic increase in novel genomic sequence information that has recently become available has generated enormous opportunities for the development of antisense oligonucleotides capable of altering the expression level of virtually any gene. With this will come a nearly equal opportunity to determine the role of individual proteins in a vast array of cardiovascular disease. The great specificity that these compounds exhibit in vitro suggests that they may also have an exciting future for development into therapeutics useful for the treatment of human disease. This review highlights some of the advances made in the field of antisense research, placing an emphasis on uses and proper controls.
Effect of Urate on Nitric Oxide Microcirculatory Response in the Rat Tail to Body Heating
Authors: Widanski B. , Richardson D. , Bruckner G.
Published: September 2002

Objective: The objective of this study was to determine if nitric oxide (NO)‐mediated cutaneous vasodilation depends on urate concentrations.

Methods: Capillary blood cell velocities (BCV) in the tail capillary vessels of anesthetized, heat‐stressed Sprague‐Dawley rats were measured by the videomicroscopy method, and the femoral mean arterial pressure (MAP) was recorded on a Grass polygraph. The effects of urate or urate and NO production on the above parameters were determined by using specific inhibitors of these compounds, for example, allopurinol (All) or All or N‐nitro‐L‐arginine (NNA), respectively. Urate concentrations were determined by an enzymatic, colorimetric method, and total nitrite levels were measured fluorometrically.

Results: During heat stress, All or All and NNA significantly decreased plasma urate or urate and total nitrite concentrations, respectively, and the response of vascular conductance (estimated as a ratio of BCV to MAP). Urate administration, after All and NNA pretreatment, restored plasma urate and total nitrite concentrations and increased BCV/MAP.

Conclusions: Urate at physiological concentration helps to maintain vascular conductance of cutaneous capillaries in the rat tail during body heating. The effect of urate on vascular conductance may be mediated by NO.
Blood Flow and Red Blood Cell Deformation in Nonuniform Capillaries: Effects of the Endothelial Surface Layer
Authors: SECOMB T.W. , HSU R. , PRIES A.R.
Published: September 2002

Objective: A theoretical model is used to examine the mechanics of red blood cell (RBC) motion in nonuniform capillaries. The model includes effects of the endothelial surface layer (ESL), which is a layer of macromolecules adjacent to the endothelium and which impedes plasma flow.

Methods: The motion of an RBC traversing a capillary with diameter varying sinusoidally between 5.4 µm and 7.4 µm is simulated numerically. The ESL is assumed to be 0.7‐µm wide and deformable. Axisymmetric RBC shapes are assumed. Lubrication theory is used to analyze the motion of plasma around the RBC and through the ESL.

Results: In a nonuniform capillary with no ESL, moving RBCs undergo large transient deformations and predicted flow resistance is substantially higher than in a uniform capillary with the same mean diameter. The presence of a deformable ESL reduces the transient fluid shear stresses and deformations experienced by RBCs traversing a nonuniform capillary. With an ESL, the increase in flow resistance resulting from nonuniformity is less than twofold versus three‐ to fourfold with no ESL in vessel geometries with the same ESL‐free luminal region.

Conclusions: The presence of the ESL reduces the impact of capillary irregularity on flow resistance and may protect RBCs traversing irregular capillaries from damage due to large, rapidly fluctuating external stresses.
The Physiology of Endothelial Xanthine Oxidase: From Urate Catabolism to Reperfusion Injury to Inflammatory Signal Transduction
Authors: MENESHIAN AVEDIS , BULKLEY GREGORY B.
Published: September 2002

Xanthine oxidoreductase (XOR) is a ubiquitous metalloflavoprotein that appears in two interconvertible yet functionally distinct forms: xanthine dehydrogenase (XD), which is constitutively expressed in vivo; and xanthine oxidase (XO), which is generated by the posttranslational modification of XD, either through the reversible, incremental thiol oxidation of sulfhydryl residues on XD or the irreversible proteolytic cleavage of a segment of XD, which occurs at low oxygen tension and in the presence of several proinflammatory mediators. Functionally, both XD and XO catalyze the oxidation of purines to urate. However, whereas XD requires NAD+ as an electron acceptor for these redox reactions, thereby generating the stable product NADH, XO is unable to use NAD+ as an electron acceptor, requiring instead the reduction of molecular oxygen for this purine oxidation and generating the highly reactive superoxide free radical. Nearly 100 years of study has documented the physiologic role of XD in urate catabolism. However, the rapid, posttranslational conversion of XD to the oxidantgenerating form XO provides a possible physiologic mechanism for rapid, posttranslational, oxidant‐mediated signaling. XO‐generated reactive oxygen species (ROS) have been implicated in various clinicopathologic entities, including ischemia/reperfusion injury and multisystem organ failure. More recently, the concept of physiologic signal transduction mediated by ROS has been proposed, and the possibility of XD to XO conversion, with subsequent ROS generation, serving as the trigger of the microvascular inflammatory response in vivo has been hypothesized. This review presents the evidence and basis for this hypothesis.