The esthetic effects of implant platform selection.

Implant dentistry has undergone considerable evolution over the history of modern endosseous implant therapy. With the advent of enhanced bone and soft tissue manipulation procedures, improved implant hardware components, and enough experience for the procedures to evolve, an implant restoration today may be indistinguishable from a natural tooth. Guidelines are discussed for implant selection and implant placement dictated by the desired functional and esthetic result. The implant platform should be selected only after the tooth and soft tissue dimensions are decided. In addition, the largest platform diameter that fits within the normal root contours should be selected. Surgically, that platform should be placed 3 mm apically and 1 mm lingually to the buccal emergence point. The buccal cementoenamel junction or free gingival margin thus becomes the key determinant for implant position. Specific implant dimensions are discussed for each tooth to provide appropriate guidelines for the practitioner.

Mechanisms of guanylin action via cyclic GMP in the kidney.

Guanylin, uroguanylin, and lymphoguanylin are small peptides that activate cell-surface guanylate cyclase receptors and influence cellular function via intracellular cGMP. Guanylins activate two receptors, GC-C and OK-GC, which are expressed in intestine and/or kidney. Elevation of cGMP in the intestine elicits an increase in electrolyte and water secretion. Activation of renal receptors by uroguanylin stimulates urine flow and excretion of sodium, chloride, and potassium. Intracellular cGMP pathways for guanylins include activation of PKG-II and/or indirect stimulation of PKA-II. The result is activation of CFTR and/or C1C-2 channel proteins to enhance the electrogenic secretion of chloride and bicarbonate. Similar cellular mechanisms may be involved in the renal responses to guanylin peptides. Uroguanylin serves as an intestinal natriuretic hormone in postprandial states, thus linking the digestive and renal organ systems in a novel endocrine axis. Therefore, uroguanylin participates in the complex physiological processes underlying the saliuresis that is elicited by a salty meal.

Guanylin peptides: renal actions mediated by cyclic GMP.

The guanylin family of cGMP-regulating peptides has three subclasses of peptides containing either three intramolecular disulfides found in bacterial heat-stable enterotoxins (ST), or two disulfides observed in guanylin and uroguanylin, or a single disulfide exemplified by lymphoguanylin. These small, heat-stable peptides bind to and activate cell-surface receptors that have intrinsic guanylate cyclase (GC) activity. Two receptor GC signaling molecules have been identified that are highly expressed in the intestine (GC-C) and/or the kidney (OK-GC) and are selectively activated by the guanylin peptides. Stimulation of cGMP production in renal target cells by guanylin peptides in vivo or ex vivo elicits a long-lived diuresis, natriuresis, and kaliuresis. Activation of GC-C receptors in target cells of intestinal mucosa markedly stimulates the transepithelial secretion of Cl(-) and HCO(-)/(3), causing enhanced secretion of fluid and electrolytes into the intestinal lumen. Bacterial ST peptides act as mimics of guanylin and uroguanylin in the intestine, which provide a cellular mechanism underlying the diarrhea caused by ST-secreting strains of Escherichia coli. Uroguanylin and guanylin may participate in a novel endocrine axis linking the digestive system and kidney as a physiological mechanism that influences Na(+) homeostasis. Guanylin, uroguanylin, and/or lymphoguanylin may also serve within intrarenal signaling pathways controlling cGMP production in renal target cells. Thus we propose that guanylin regulatory peptides participate in a complex multifactorial biological process that evolved to regulate the urinary excretion of NaCl when dietary salt levels exceed the body's physiological requirements. This highly integrated and redundant mechanism allows the organism to maintain sodium balance by eliminating excess NaCl in the urine. Uroguanylin, in particular, may be a prototypical "intestinal natriuretic hormone."

Guanylin peptides: cyclic GMP signaling mechanisms.

Guanylate cyclases (GC) serve in two different signaling pathways involving cytosolic and membrane enzymes. Membrane GCs are receptors for guanylin and atriopeptin peptides, two families of cGMP-regulating peptides. Three subclasses of guanylin peptides contain one intramolecular disulfide (lymphoguanylin), two disulfides (guanylin and uroguanylin) and three disulfides (E. coli stable toxin, ST). The peptides activate membrane receptor-GCs and regulate intestinal Cl- and HCO3- secretion via cGMP in target enterocytes. Uroguanylin and ST also elicit diuretic and natriuretic responses in the kidney. GC-C is an intestinal receptor-GC for guanylin and uroguanylin, but GC-C may not be involved in renal cGMP pathways. A novel receptor-GC expressed in the opossum kidney (OK-GC) has been identified by molecular cloning. OK-GC cDNAs encode receptor-GCs in renal tubules that are activated by guanylins. Lymphoguanylin is highly expressed in the kidney and heart where it may influence cGMP pathways. Guanylin and uroguanylin are highly expressed in intestinal mucosa to regulate intestinal salt and water transport via paracrine actions on GC-C. Uroguanylin and guanylin are also secreted from intestinal mucosa into plasma where uroguanylin serves as an intestinal natriuretic hormone to influence body Na+ homeostasis by endocrine mechanisms. Thus, guanylin peptides control salt and water transport in the kidney and intestine mediated by cGMP via membrane receptors with intrinsic guanylate cyclase activity.

Guanylin peptides: cyclic GMP signaling mechanisms

Guanylate cyclases (GC) serve in two different signaling pathways involving cytosolic and membrane enzymes. Membrane GCs are receptors for guanylin and atriopeptin peptides, two families of cGMP-regulating peptides. Three subclasses of guanylin peptides contain one intramolecular disulfide (lymphoguanylin), two disulfides (guanylin and uroguanylin) and three disulfides (E. coli stable toxin, ST). The peptides activate membrane receptor-GCs and regulate intestinal Cl- and HCO3- secretion via cGMP in target enterocytes. Uroguanylin and ST also elicit diuretic and natriuretic responses in the kidney. GC-C is an intestinal receptor-GC for guanylin and uroguanylin, but GC-C may not be involved in renal cGMP pathways. A novel receptor-GC expressed in the opossum kidney (OK-GC) has been identified by molecular cloning. OK-GC cDNAs encode receptor-GCs in renal tubules that are activated by guanylins. Lymphoguanylin is highly expressed in the kidney and heart where it may influence cGMP pathways. Guanylin and uroguanylin are highly expressed in intestinal mucosa to regulate intestinal salt and water transport via paracrine actions on GC-C. Uroguanylin and guanylin are also secreted from intestinal mucosa into plasma where uroguanylin serves as an intestinal natriuretic hormone to influence body Na+ homeostasis by endocrine mechanisms. Thus, guanylin peptides control salt and water transport in the kidney and intestine mediated by cGMP via membrane receptors with intrinsic guanylate cyclase activity.

Rate of pull-out strength gain of dual-etched titanium implants: a comparative study in rabbits.

The purpose of this study was to investigate the rate of pull-out strength gain of an etched titanium implant surface. Rabbit tibiae were used to compare machined titanium and proprietary dual-etched titanium implants. Two custom cylindric implants (3 mm in diameter and 4 mm in length) were placed in each right anteromedial tibia in 31 rabbits. At weeks 1, 2, 3, 4, 5, and 8, the implants in 5 rabbits were subjected to failure shear loading in a pull-out test. For shear failure testing, each tibial segment was mounted in a precision alignment jig, and an Instron pull-out test was performed on each implant. Beginning at week 3, there was a statistically significant difference (P < .01) between the dual-etched and the machined implants. There was a significant increase in strength for dual-etched implants between week 5 and week 8, while the machined implants did not show an increase during this time interval. The etched implants maintained a significantly greater pull-out strength for the remainder of the study, with a 3.2-fold greater mean strength at 8 weeks, equivalent to 6 months in humans. At 3 weeks, the etched implant's strength exceeded the strength that the machined implant had achieved at 8 weeks. In short-term healing in the rabbit tibia, the dual-etched surface demonstrated a more rapid rate of pull-out strength gain than the machined surface and remained significantly stronger throughout the 8 weeks of the study.

Structure and activity of OK-GC: a kidney receptor guanylate cyclase activated by guanylin peptides.

Uroguanylin, guanylin, and lymphoguanylin are small peptides that activate renal and intestinal receptor guanylate cyclases (GC). They are structurally similar to bacterial heat-stable enterotoxins (ST) that cause secretory diarrhea. Uroguanylin, guanylin, and ST elicit natriuresis, kaliuresis, and diuresis by direct actions on kidney GC receptors. A 3,762-bp cDNA characterizing a uroguanylin/guanylin/ST receptor was isolated from opossum kidney (OK) cell RNA/cDNA. This kidney cDNA (OK-GC) encodes a mature protein containing 1,049 residues sharing 72.4-75.8% identity with rat, human, and porcine forms of intestinal GC-C receptors. COS or HEK-293 cells expressing OK-GC receptor protein were activated by uroguanylin, guanylin, or ST13 peptides. The 3.8-kb OK-GC mRNA transcript is most abundant in the kidney cortex and intestinal mucosa, with lower mRNA levels observed in urinary bladder, adrenal gland, and myocardium and with no detectable transcripts in skin or stomach mucosa. We propose that OK-GC receptor GC participates in a renal mechanism of action for uroguanylin and/or guanylin in the physiological regulation of urinary sodium, potassium, and water excretion. This renal tubular receptor GC may be a target for circulating uroguanylin in an endocrine link between the intestine and kidney and/or participate in an intrarenal paracrine mechanism for regulation of kidney function via the intracellular second messenger, cGMP.

Lymphoguanylin: cloning and characterization of a unique member of the guanylin peptide family.

Guanylin and uroguanylin are small peptides containing two disulfide bonds that activate membrane guanylate cyclase-receptors in the intestine, kidney and other epithelia. Hybridization assays with a uroguanylin complementary DNA (cDNA) detected uroguanylin-like messenger RNAs (mRNAs) in the opossum spleen and testis, but these transcripts are larger than uroguanylin mRNAs. RT of RNA from spleen to produce cDNAs for amplification in the PCR followed by cloning and sequencing revealed a novel lymphoid-derived cDNA containing an open reading frame encoding a 109-amino acid polypeptide. This protein shares 84% and 40% of its residues with preprouroguanylin and preproguanylin, respectively. A 15-amino acid, uroguanylin-like peptide occurs at the COOH-terminus of the precursor polypeptide. However, this peptide is unique in having only three cysteine residues. We named the gene and its peptide product lymphoguanylin because the source of the first cDNA isolated was spleen and its mRNA is expressed in all of the lymphoid tissues tested. A 15-amino acid form of lymphoguanylin containing a single disulfide bond was synthesized that activates the guanylate cyclase receptors of human T84 intestinal and opossum kidney (OK) cells, although with less potency than uroguanylin and guanylin. Northern and/or RT-PCR assays detected lymphoguanylin mRNA transcripts in many tissues and organs of opossums, including those within the lymphoid/immune, cardiovascular/renal, reproductive, and central nervous organ systems. Lymphoguanylin joins guanylin and uroguanylin in a growing family of peptide agonists that activate transmembrane guanylate cyclase receptors, thus influencing target cell function via the intracellular second messenger, cGMP.

Osteotome single-stage dental implant placement with and without sinus elevation: a clinical report.

Forty-three sites in 16 patients were selected for placement of implants using osteotomes in a single-stage surgical technique. Most sites were treated to enhance bone quality. Sixteen sites in the posterior maxilla had sinus elevation performed in conjunction with implant placement. No soft tissue coverage of the implant cover screw was attempted in either the sinus-elevated or the nonelevated sites. Sinus elevation was significant relative to baseline (mean gain 3.25 mm, P < .01). The implant survival rate was 95.3%.

Evans blue dye modifies the ultrastructure of normal and regenerating arterial endothelium in rats.

Evans blue dye (EBD) identifies areas of increased vascular permeability, which is usually indicative of endothelial damage. Most studies examine EBD-stained areas light-microscopically, but others analyze the cells with the electron microscope. Electron microscopic studies have assumed that EBD itself did not change the ultrastructure of endothelial cells and this hypothesis was tested in the following study. The left iliac arteries of 20 rats were injured with 1-mm vascular clamps for 5 minutes. At 7 and 14 days after clamping, 10 rats for each time were infused intravenously either with normal-saline or EBD, perfused 30 minutes later with fixatives. Then the clamp-injured arteries, contralateral (unclamped) arteries, aortae, and the aortic bifurcations were removed for EM morphometry. In an additional (control) group of 10 rats, with no clamp injuries, 5 were infused with EBD and 5 with normal-saline and all 10 rats were perfused 30 minutes later, as above. EBD caused a significant simplification of the junctional morphology in both normal and regenerating endothelium. It also increased the area fractions of cytoplasmic vesicles in regenerating endothelium. These data demonstrate that EBD causes measurable ultrastructural changes in normal and regenerating endothelium. This effect should be taken into account when using EBD to assess various insults to blood vessels.

Regulation of intestinal Cl- and HCO3-secretion by uroguanylin.

Uroguanylin is an intestinal peptide hormone that may regulate epithelial ion transport by activating a receptor guanylyl cyclase on the luminal surface of the intestine. In this study, we examined the action of uroguanylin on anion transport in different segments of freshly excised mouse intestine, using voltage-clamped Ussing chambers. Uroguanylin induced larger increases in short-circuit current (Isc) in proximal duodenum and cecum compared with jejunum, ileum, and distal colon. The acidification of the lumen of the proximal duodenum (pH 5.0-5.5) enhanced the stimulatory action of uroguanylin. In physiological Ringer solution, a significant fraction of the Isc stimulated by uroguanylin was insensitive to bumetanide and dependent on HCO3- in the bathing medium. Experiments using pH-stat titration revealed that uroguanylin stimulates serosal-to-luminal HCO3- secretion (Js-->lHCO3-) together with a larger increase in Isc. Both Js-->lHCO3- and Isc were significantly augmented when luminal pH was reduced to pH 5.15. Uroguanylin also stimulated the Js-->lHCO3- and Isc across the cecum, but luminal acidity caused a generalized decrease in the bioelectric responsiveness to agonist stimulation. In cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice, the duodenal Isc response to uroguanylin was markedly reduced, but not eliminated, despite having a similar density of functional receptors. It was concluded that uroguanylin is most effective in acidic regions of the small intestine, where it stimulates both HCO3- and Cl-secretion primarily via a CFTR-dependent mechanisms.

Structure and activity of uroguanylin and guanylin from the intestine and urine of rats.

Uroguanylin and guanylin are related peptides that activate common guanylate cyclase signaling molecules in the intestine and kidney. Uroguanylin was isolated from urine and duodenum but was not detected in extracts from the colon of rats. Guanylin was identified in extracts from small and large intestine but was not detected in urine. Uroguanylin and guanylin have distinct biochemical and chromatographic properties that facilitated the separation, purification, and identification of these peptides. Northern assays revealed that mRNA transcripts for uroguanylin were more abundant in small intestine compared with large intestine, whereas guanylin mRNA levels were greater in large intestine relative to small intestine. Synthetic rat uroguanylin and guanylin had similar potencies in the activation of receptors in T84 intestinal cells. Production of uroguanylin and guanylin in the mucosa of duodenum is consistent with the postulate that both peptides influence the activity of an intracellular guanosine 3',5'-cyclic monophosphate signaling pathway that regulates the transepithelial secretion of chloride and bicarbonate in the intestinal epithelium.

Signaling pathways for guanylin and uroguanylin in the digestive, renal, central nervous, reproductive, and lymphoid systems.

Guanylin and uroguanylin are peptides that stimulate membrane guanylate cyclases (GC) and regulate intestinal and renal function via cGMP. Complementary DNAs were isolated encoding opossum preproguanylin and a 279-amino acid portion of a receptor-guanylate cyclase expressed in opossum kidney (OK) cells (GC-OK). The tissue expression of messenger RNA transcripts for these signaling molecules were then compared. Northern and/or reverse transcription-PCR assays revealed that guanylin, uroguanylin, and GC-OK messenger RNAs are expressed in tissues within the digestive, renal, central nervous, reproductive, and lymphoid organ systems. Receptor autoradiography localized the receptors for uroguanylin and guanylin to renal proximal tubules and seminiferous tubules of testis. Synthetic guanylin and uroguanylin peptides activated the receptor-GCs in opossum kidney cortex and in cultured OK cells eliciting increased intracellular cGMP. Expression of agonist and receptor-GC signaling molecules provides a pathway for paracrine and/or autocrine regulation of cellular functions via cGMP in the digestive, renal, central nervous, reproductive, and lymphoid/immune organ systems. Uroguanylin also links the intestine and kidney in a potential endocrine axis that activates tubular receptor-GCs and influences renal function.

Signal transduction pathways via guanylin and uroguanylin in stomach and intestine.

Guanylin and uroguanylin are peptides that activate receptor guanylate cyclases (GCs) and elicit increased intestinal secretion. Bacteria that cause traveler's diarrhea produce heat-stable toxins (STs) that mimic this action. Investigation of the distribution and identity of receptor GCs in the gastrointestinal tract of rats revealed that receptors were localized to epithelial cells in stomach and intestine. Clusters of cells in gastric mucosa and enterocytes lining the intestine exhibited specific binding of 125I-labeled ST. Ligated loops of stomach and intestine treated with intraluminal ST had significant increases in guanosine 3',5'-cyclic monophosphate (cGMP), with duodenum exhibiting the greatest response. Expression of guanylate cyclase C (GCC) mRNA and a truncated, GCC-like mRNA was found in both stomach and intestine. Both mRNAs were isolated as cDNAs encoding the GC catalytic domain. The 0.9-kilobase (kb) cDNA is 99.8% identical to GCC, whereas the truncated, 0.75-kb GCC-like cDNA has a 159-nucleotide deletion and is 96.6% identical to GCC at the protein level. Uroguanylin and guanylin mRNAs were detected in stomach and intestine. Uroguanylin mRNA was most abundant in small intestine, whereas guanylin mRNA was highest in large intestine. Thus the stomach and intestine are targets for regulation of transport by guanylin and uroguanylin via cGMP.

The guanylin and uroguanylin peptide hormones and their receptors.

Guanylin and uroguanylin are newly discovered, related peptides that activate common guanylyl cyclase signaling molecules and via 3', 5'-guanosine cyclic monophosphate regulate the activity of a variety of tissues and organs. Additionally, the message for both peptides is expressed in a variety of tissues and organs, including the intestinal tract and kidney, and thus may serve as part of a functional endocrine axis linking these two major organ systems in fluid/volume homeostasis. This manuscript reviews the discovery and nature of the guanylin and uroguanylin peptides, their actions on the intestinal mucosa and kidney, the distribution and molecular biology of the guanylyl cyclase C receptor, and explores the future directions of this rapidly developing, expanding field of inquiry.

The dynamics of microbial colonization of barrier membranes for guided tissue regeneration.

The microbial colonization of expanded polytetrafluoroethylene membrane by putative periodontopathogens at 3 minutes of intraoral manipulation was determined in 42 patients with 42 mandibular posterior two- to three-wall defects. Twenty patients exhibited no periodontal pockets of > or = 5 mm, other than the study site, and low levels of pathogens (group A). Twenty-two patients revealed multiple periodontal pockets of 5 mm or more and numerous pathogens (group B). Within the preceding 3 months of regenerative surgery, group A patients had received apically positioned flap surgery with osseous recontouring (except for the study site), and group B patients had been enrolled in a non-surgical maintenance program. The subgingival microbiota was examined prior to regenerative therapy, and the membrane microbiota was examined at 3 minutes and at the time of removal at 6 weeks by culture, DNA probes, and phase-contrast microscopy. The mean initial defect depth was 7.4 mm for group A and 7.2 mm for group B. At 6 months, the difference in mean clinical attachment gain was statistically significant (P < 0.001; group A: 3.4 mm; group B: 1.4 mm). At 3 minutes, putative pathogens were detected in seven (16.7%) membranes in group B (group Binfected), and the associated sites gained only 0.6 mm in clinical attachment at 6 months. Clinical attachment gain was modeled as a linear function of the explanatory variables (r2 = 86%). The presence of Porphyromonas gingivalis detected by DNA probe at 3 minutes was associated with 1.5 mm less expected gain (P = 0.0002). Total microbial counts and the percentage of Peptostreptococcus micros and Capnocytophaga species at baseline, and of motile rods on the membrane surface facing the gingiva at 6 weeks, were statistically significant negative predictors of clinical attachment. For each week the membrane remained covered, an additional 0.5 mm gain could be expected (P = 0.002); and for every 10 sites that exhibited bleeding on probing, the clinical attachment gain was 0.6 mm less at the site of regeneration (P < 0.0001). The present results showed that putative pathogens may colonize membranes within 3 minutes of intraoral manipulation. The patient group treated with periodontal osseous surgery revealed the lowest levels of periodontal pathogens in the membranes and exhibited the most gain in clinical attachment.

Planning for implant placement.

Successful implant placement requires extensive planning. Evaluation of medical and intraoral conditions to determine eligibility, combined with a thorough periodontal and dental assessment and radiographic evaluation, will provide valuable information in planning and completing effective implant cases.