Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner.

Ischemia/reperfusion (I/R) injury is a major cause of morbidity and mortality after liver surgery. The role of Sirtuin 1 (SIRT1) in hepatic I/R injury remains elusive. Using human and mouse livers, we investigated the effects of I/R on hepatocellular SIRT1. SIRT1 expression was significantly decreased after I/R. Genetic overexpression or pharmacological activation of SIRT1 markedly suppressed defective autophagy, onset of the mitochondrial permeability transition, and hepatocyte death after I/R, whereas SIRT1-null hepatocytes exhibited increased sensitivity to I/R injury. Biochemical approaches revealed that SIRT1 interacts with mitofusin-2 (MFN2). Furthermore, MFN2, but not MFN1, was deacetylated by SIRT1. Moreover, SIRT1 overexpression substantially increased autophagy in wild-type cells, but not in MFN2-deficient cells. Thus, our results demonstrate that the loss of SIRT1 causes a sequential chain of defective autophagy, mitochondrial dysfunction, and hepatocyte death after I/R.

Clinical anatomy of the atrioventricular junctions.

OBJECTIVES: This study reevaluated the anatomy of the areas anterior and posterior to the atrioventricular (AV) septal structures, previously said to represent anterior and posterior septal areas. BACKGROUND: In descriptions of the locations of accessory AV pathways within the AV junctions, four regions have been recognized: the left and right free walls and the anterior and posterior septums. On the basis of known facts concerning cardiac structure, it is questionable whether these so-called septums are truly septal. METHODS: Ten human hearts were dissected to elucidate the clinical anatomy of these purportedly septal regions, together with the overall arrangement of the AV junctions. RESULTS: The true septal components of the AV junctions are the muscular and membranous AV septal areas. These separate the cavity of the right atrium from that of the left ventricle. The region previously designated as the anterior septum is part of the right parietal junction. It is contiguous with the membranous part of the septum but extends anteriorly and laterally from the septum as part of the supraventricular crest of the right ventricle ("crista supraventricularis"). In the region posterior to and beneath the mouth of the coronary sinus, only the most anterior extent, in continuity with the central fibrous body, is part of the muscular AV septum. The posterior extent of this area roofs over the diverging right and left ventricular walls and is filled in with fibroareolar tissue of the AV groove. CONCLUSIONS: The larger part of the regions anterior and posterior to the true AV septal areas are not septal but are parts of the parietal AV junctions. An understanding of these anatomic relations is essential for those wishing to modify conduction across the AV junctions.

Effect of changes in load on monophasic action potential and segment length of pig heart in situ.

There is increasing evidence that mechano-electric feedback, defined as a change in mechanical state that precedes and alters transmembrane potential, operates in a wide variety of preparations and species including man. Load reduction is becoming a common therapeutic tool in a variety of clinical settings but the electrophysiological effects of these manoeuvres is not known. In this study the effect of changes in loading conditions on the time course of ventricular repolarisation were examined in the in situ heart in 13 pigs anaesthetised with halothane. Monophasic action potentials, electrocardiograms and segment length changes were recorded from the left ventricular epicardium using suction operated devices. Afterload was decreased by intravenous infusion of sodium nitroprusside, and increased by aortic cross clamping. Infusion of sodium nitroprusside resulted in a rise in action potential duration (measured at 70% repolarisation) in all 21 infusions (mean 3.4 ms), which was linearly related to the fall in systolic left ventricular pressure (r = 0.72, p less than 0.001) and the change in minimum systolic segment length (r = 0.46, p less than 0.05), but not to the change in maximum diastolic length (r = 0.33, NS). Aortic constriction, sufficient to elevate peak systolic left ventricular pressure back to the control level, restored the changes in action potential duration to normal. In addition, there were concomitant changes in the QT interval and T wave of the epicardial ECG. These findings show that mechano-electric feedback operates in the in situ heart and has potential importance in the clinical setting where changes in systemic blood pressure may directly alter cardiac electrophysiology.

Audit of cardiac catheterisation in a district general hospital: implications for training.

OBJECTIVE: To assess complications of diagnostic cardiac catheterisation in a non-surgical centre by review of the first three years' experience and audit of 2804 diagnostic left heart procedures. DESIGN: Analysis of a prospective database of cardiac catheter procedures. SETTING: District general hospital without available on site cardiac surgery. RESULTS: The rate of major complications of cardiac catheterisation was 0.07%. Mortality was 0. 07%, and the rate of arterial complications (requiring surgical repair) was 0.24% for brachial arteries and 0.17% for femoral. These results are comparable to those reported from national and international surgical centres. CONCLUSION: A diagnostic cardiac catheterisation service can be offered in non-surgical hospitals without an increased risk to patients. It highlights the relevance of training in angioplasty and questions the appropriateness of starting preliminary invasive cardiology training of specialist registrars in district general hospitals.

Myocardial infarction due to coronary artery compression by aortic root abscess.

A 44-year-old man with aortic valve disease presented with myocardial ischaemia and ultimately infarction in the presence of suspected endocarditis. Thoracic computerised tomographic scan and coronary arteriography suggested the ischaemia was caused by external compression of the left coronary artery due to an aortic root abscess, later confirmed at surgery. Myocardial ischaemia is an infrequent accompaniment of infective endocarditis and is most commonly due to coexisting coronary disease. More rarely, emboli from vegetations may give rise to infarction. Although aortic root abscess is a well recognised complication of aortic valve endocarditis, coronary artery compression is an unusual mode of presentation and we believe this to be the first reported case of myocardial infarction resulting from external compression in this setting.

Osteotome sinus floor elevation and simultaneous, non-submerged implant placement: case report and literature review.

The osteotome sinus floor elevation is a conservative technique for sinus elevation and immediate implant placement. The purpose of this report is to present a case using the sinus floor elevation technique for placement of a non-submerged implant with 12 months follow-up after permanent restoration and to review the literature regarding sinus floor elevation. The osteotome sinus floor elevation technique may be used successfully for the placement of nonsubmerged implants. It allows for shorter post-treatment waiting times and provides a less invasive approach compared to 1- or 2-step antrostomy procedures.

Migration of gingival fibroblasts on fibronectin and laminin.

The migrational behavior of fibroblasts is critical for the maintenance and healing of the periodontium. The purpose of this study was to determine, in vitro, the differences found in gingival fibroblast migration on the following substrates: fibronectin, laminin, bovine serum albumin (BSA), or plastic. Filter paper strips soaked in solutions of the test molecules were placed in 35 mm culture dishes. Equimolar amounts of the various proteins were allowed to dry onto the plastic in a discrete band. The bands were masked and 5.0 x 10(4) cells seeded. Rat gingival fibroblasts were allowed to attach for 1.5 hours and the protein bands uncovered and incubation continued for 24 hours under standard conditions. Cells were fixed, stained and cell images captured, computer digitized and migrational areas and cell numbers and areas quantified after converting pixels to microm. Cell migration was enhanced on fibronectin substrates. Statistically significant differences (P < 0.01) were found for total area covered (fibronectin, mean = 110.8 mm2 vs. controls: plastic, mean = 28.2 mm2; BSA, mean = 18.2 mm2) and the number of cells migrating as compared to controls (fibronectin, mean = 1184 vs. controls: plastic, mean = 304, BSA, mean = 230). No significant differences in area covered or numbers of cells migrating were found between controls and cells exposed to other substrates. Mean spread area per cell was not statistically significantly different for any of the conditions. Numbers of cells migrating on substrates other than fibronectin were reduced even more when protein synthesis was inhibited using cycloheximide. In this system fibronectin serves as a cue to recruit significantly greater numbers of fibroblasts to migrate for greater distances than the other molecules tested.

Attachment of Fusobacterium nucleatum to fibronectin immobilized on gingival epithelial cells or glass coverslips.

To learn more about colonization of the oral epithelium by Fusobacterium nucleatum and the role of fibronectin in mediating adhesion of this microorganism, we studied attachment of this bacterium to cultured gingival epithelial cells that were coated with exogenous, purified plasma fibronectin. The three strains of F. nucleatum studied adhered in large numbers to epithelial cells that had been coated with fibronectin, compared with buffer-coated control cells. Bacterial adherence was also enhanced when epithelial cells were coated with whole human saliva. However, cells coated with saliva depleted of fibronectin did not facilitate adhesion of bacteria. Bacterial adhesion was restored when purified fibronectin was added back. We also tested adherence of bacteria to coverslips coated with fibronectin, saliva, and saliva depleted of fibronectin. The bacteria adhered to coverslips coated with fibronectin or whole human saliva, but did not adhere to coverslips coated with fibronectin-depleted saliva. Bacterial adhesion to coverslips was restored upon addition of purified fibronectin to the fibronectin-depleted saliva. Bacterial attachment to fibronectin-coated coverslips was found to be temperature-dependent, with maximal adhesion observed at 37 degrees C. Pre-treatment of F. nucleatum with soluble fibronectin inhibited attachment of the bacteria by 92%, whereas pre-treatment with bovine serum albumin had no effect. Pre-treatment of bacteria with laminin or type IV collagen caused moderate inhibition of attachment by 60% and 50%, respectively. Treatment of fibronectin-coated coverslips with Fab fragments of anti-fibronectin IgG blocked the attachment of F. nucleatum by 93%. Fab fragments of the other antisera tested had no inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

The survival rate of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Bacteroides forsythus following 4 randomized treatment modalities.

The overall goal of this clinical study was to determine the short-term anti-infective effects of four randomized treatment modalities on Actinobacillus actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), and Bacteroides forsythus (Bf) and determine the effects of bacterial survival on treatment outcomes in patients with adult periodontitis. Twelve adult patients requiring therapy for moderate periodontitis were selected for this study. All patients had at least one tooth in each quadrant that had an inflamed pocket of probing depth > or =5 mm with probing attachment loss that harbored at least one of the following three periodontal pathogens: Aa, Pg, or Bf. The number of target organisms per site was determined pre-operatively, at 1 week, and 1 month and 3 months postoperatively utilizing DNA probes. One quadrant in each patient was randomly assigned to each one of the following four treatment groups: 1) scaling and root planing (SRP group); 2) pocket reduction through osseous surgery and apically-positioned flap (OS group); 3) modified Widman flap (MWF group); and 4) modified Widman flap and topical application of saturated citric acid at pH 1 for 3 minutes (CA group). The 4 treatment modalities were performed in one appointment. No postoperative antibiotics were used. Patients were instructed to supplement their daily oral hygiene with chlorohexidine oral rinse during the study. The results of this investigation indicated that: 1) none of the treatment modalities was effective in eliminating the target species; 2) the incidence of infected sites for all groups was 100% preoperatively; 62.5%, 33.3%, and 31.3% at 1 week, and 1 and 3 months postoperatively, respectively; 3) these infected sites lost 1.1 +/- 0.4 mm of probing attachment compared to gain of 0.0 +/- 0.3 mm for uninfected sites; 4) the infected sites had higher plaque and bleeding on probing 0.9 +/- 0.3, 73 +/- 12%, respectively, compared to 0.3 +/- 0.1 and 30 +/- 8% for the uninfected sites; and 5) no statistically significant differences were detected among the infected sites in regard to gingival index (1.0 +/- 0.2 vs. 0.8 +/- 0.1) or probing depth (3.5 +/- 0.4 vs. 3.0 +/- 0.1 mm). These results indicate that bacterial survival negatively affects the short-term clinical outcomes of non-surgical and surgical periodontal therapy.

The prevalence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Bacteroides forsythus in humans 1 year after 4 randomized treatment modalities.

The relationship between probing attachment changes in treated periodontal pockets and the prevalence of selected periodontal pathogens was assessed in 10 patients with adult periodontitis 1 year following randomized therapy. All patients had at least 1 tooth in each quadrant with an inflamed pocket of probing depth > or =5 mm and clinical attachment loss and harbored at least one of the following 3 major periodontal pathogens: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, or Bacteroides forsythus. The number of target organisms per site was determined preoperatively; at 1 week; and at 1, 3, 6, and 12 months postoperatively utilizing DNA probes. The following clinical parameters were measured and recorded preoperatively and at 1, 3, 6, and 12 months post-treatment: gingival fluid flow, gingival index, plaque index, probing depth, probing attachment level, gingival recession, and bleeding on probing. One quadrant in each patient was randomly assigned to 1 of the following 4 treatments: 1) scaling and root planing; 2) pocket reduction through osseous surgery and apically-positioned flap; 3) modified Widman flap; and 4) modified Widman flap and topical application of saturated citric acid at pH 1 for 3 minutes. All 4 treatments were rendered in one appointment using local anesthesia. No postoperative antibiotics were used, but patients rinsed with 0.12% chlorhexidine for the first 3 months postoperatively and received a prophylaxis every 3 months. This investigation revealed: 1) 30.0% of the sites were infected by at least 1 species at 3, 6, and 12 months postoperatively. 2) Failing sites were infected by a high number of both Pg and Bf These sites had a mean of 24.2+/-9.0 x 10(3) Pg and 93.1+/-42.0 X 10(3) Bf while stable sites had a mean of 6.8+/-0.5 x 10(3) Pg and 7.2+/-1.2 x 10(3) Bf (P = 0.06 and P = 0.05, respectively). 3) The infected sites lost significantly more mean clinical attachment at 12 months (1.5+/-0.5 mm compared to a loss of 0.2+/-0.3 mm for uninfected sites, P = 0.017). 4) The infected sites had a significantly greater BOP (67+/-14% versus 25+/-8% for uninfected sites at 12 months, P = 0.012). 5) The choice of treatment modality did not affect the prevalence of the target species at 1 year post-treatment. These results suggest that prevalence of microbial pathogens negatively affects the 1 year outcome of periodontal surgical and nonsurgical therapy.

Effect of smear layer and direction of dentinal tubules on osteoblast adhesion to human dentin tissue.

The purpose of this study was to investigate the effect of smear layer and direction of dentinal tubules on osteoblast adhesion to human dentin tissue in vitro. Dentin disks were made from human premolars extracted for orthodontic reasons. Dentin disks were cut either perpendicularly to the long axis of the tooth or at 45 degrees to the long axis of tooth. The smear layer was removed by 34% phosphoric acid gel from half of the dentin disk surface. Human osteoblast-like Saos-2 cells were grown in RPMI medium with 10% fetal bovine serum and 1% antibiotic/antimycotic cocktail under standard cell culture conditions. Cells were seeded into Nunc four-well culture plates at 1.5 x 10(5) cells per well with dentin disks in the bottom of each well. After 1 day in culture the dentin disks along with cells grown on their surface were examined with a scanning electron microscopy. Osteoblasts attached and spread on the dentin surface and formed a monolayer in the presence and absence of a smear layer. Cells spread over the dentinal tubules despite their direction. These results suggest that cell adhesion and spreading of osteoblasts is not influenced either by the existence of a smear layer or the direction of the dentinal tubules on the dentin surface.

Evaluation of a combined surgical repair and guided tissue regeneration technique to treat recent root canal perforations.

This study evaluated a technique that included retrofill to repair molar root canal perforations and guided tissue regeneration to restore the periodontium that was removed from the furcation area for access to the sites. Six dogs had root canal therapy on mandibular fourth premolars and first molars. The distal root of each tooth was perforated on the furcation aspect halfway between the furcation and the apex. Replaced flap surgery was performed for access to prepare and fill the perforation site with intermediate Restorative Material. A bone xenograft was placed in the access ostectomy site and covered with GoreTex Augmentation Material (GTAM). Controls included unfilled perforations and not using bone grafts and/or GTAM. Dogs were killed at 6, 12, and 24 wk postsurgery. Complications were more common when root perforations were left unfilled. Histomorphometry revealed a statistically significant decrease in inflammation and more bone fill when root perforations were filled and GTAM was used, respectively.

Fibronectin and laminin enhance gingival cell attachment to dental implant surfaces in vitro.

The objective of this study was to determine if the biologically active molecules laminin and fibronectin could influence gingival cell attachment to implant surfaces in vitro. Flat squares of the following implant materials were tested: smooth, plasma-sprayed, and hydroxyapatite-coated titanium. The surfaces were coated with equimolar quantities of either laminin, fibronectin, or bovine serum albumin. Fibronectin coating of implant surfaces resulted in two to three times the enhancement of gingival fibroblast binding on all implant surfaces tested (P < .01), with a lesser effect on epithelial cells. Laminin coating resulted in three to four times the enhancement of gingival epithelial cell binding on all implant surfaces tested (P < .01), with a lesser effect on fibroblasts. The two cell types exhibited distinct preferences for the different molecules tested with the surface roughness having some influence.

A combined endodontic retrofill and periodontal guided tissue regeneration technique for the repair of molar endodontic furcation perforations: report of a case.

This is a report of a case in which the techniques of endodontic retrofill and guided tissue regeneration were used together to treat a perforation of the mesiofacial root of a maxillary left first molar (a strip perforation). After full-thickness flap reflection, the root received a retrograde filling and a large fenestration defect was surgically created to allow access to the furcal (distal) surface of the mesiofacial root. The roots were treated with tetracycline, the defect was filled with freeze-dried, demineralized, irradiated human cadaver bone, and the access fenestration was covered with a piece of barrier membrane. Healing was uneventful and the defect showed 100% bone fill at the time of reentry to retrieve the membrane 7 months after the initial surgery. Fifteen months after surgery the area appears clinically and radiographically healthy and the tooth has been employed as an abutment for a fixed partial denture.

Beyond quality circles: self-managing teams.

A more extreme form of change than QCs, self-managing teams are informally estimated to have evolved in more than 200 U.S. plants. Indications are, however, that this is but the beginning--despite middle managers' fears that such teams will erode their power.

Exaggerated responsiveness to thyrotrophin releasing hormone: a risk factor in women with coronary artery disease.

Thyroid function tests were performed and thyroid antibodies and serum cholesterol concentrations measured in 12 women aged 60 years or under with severe coronary artery disease proved by coronary angiography. This group was compared with 11 women with normal coronary angiography. Ten out of the 12 women with coronary artery disease had an exaggerated response of thyroid stimulating hormone to thyrotrophin releasing hormone compared with two out of 11 controls (p less than 0.008). The mean serum cholesterol concentration was significantly higher in those with coronary artery disease than in the controls. Thyroid antibodies were present in four of those with coronary artery disease and one of the controls. There was no difference in the risk factors for coronary artery disease between the two groups except for cigarette smoking. Eleven out of 12 in the coronary artery disease group smoked cigarettes compared with four out of 11 in the control group (p less than 0.01). Minimal impairment of thyroid function is an important risk factor for coronary artery disease in women.

Abnormal ventricular repolarisation in association with myocardial bridging.

Myocardial bridging causing systolic compression of epicardial coronary arteries may be an incidental finding at coronary arteriography. Bridging rarely causes myocardial ischaemia. A young man presented with chest pain and striking abnormalities of ventricular repolarisation that initially were treated as myocardial infarction. At cardiac catheterisation the coronary arteries were normal apart from the presence of a myocardial bridge affecting a major diagonal branch of the left anterior descending artery. Echocardiography was normal with no features of hypertrophic cardiomyopathy.

Regional changes in ventricular excitability during load manipulation of the in situ pig heart.

1. The effect of load manipulation on myocardial excitability was studied in the anaesthetized, in situ pig heart. 2. A 33% increase in systolic left ventricular pressure achieved by aortic clamping reduced the mean effective refractory period by 11 ms (7.6%, P less than 0.01); whereas a 15% reduction in ventricular pressure achieved by intravenous infusion of sodium nitroprusside increased the mean effective refractory period by 4 ms (3.2%, P less than 0.05). 3. Changes in action potential duration, measured to 70% repolarization, roughly paralleled those of the effective refractory period. 4. The changes in effective refractory period were inhomogeneous, with a greater change occurring at the apex compared to the base in response to an increase in load, i.e. there was an increase in regional dispersion of refractoriness across the left ventricle. 5. Since inhomogeneity of repolarization and refractoriness is known to be potentially arrhythmogenic, these findings suggest that mechanical factors may contribute directly to the arrhythmias commonly seen clinically in high load states such as congestive cardiac failure and may also have consequences for the treatment of such arrhythmias.

Arrhythmia in heart failure: role of mechanically induced changes in electrophysiology.

Various mechanisms have been suggested to explain the high prevalence of ventricular arrhythmia in patients with heart failure, but as yet there is no unifying theory. There is growing evidence that changes in myocardial mechanical properties may directly alter cardiac electrophysiology by a process of mechanoelectric feedback. Moreover, when changes in cardiac loading similar to those seen in heart failure are produced experimentally in normal heart, there is a greater tendency to arrhythmogenesis. The intimate relation between changes in mechanical function and arrhythmia in heart failure could account for the lack of effect of most conventional antiarrhythmic drugs on arrhythmogenesis, and the beneficial effect of peripheral vasodilators. This paper argues that mechanically induced changes in electrophysiology are very important in the development of arrhythmia in cardiac failure; there may be no need to implicate other mechanisms, such as relative ischaemia, metabolic changes, or changes in sympathetic tone.