Pharmacology and Therapeutic Potential of the 5-HT Receptor.

It is well-documented that serotonin (5-HT) exerts its pharmacological effects through a series of 5-HT receptors. The most recently identified member of this family, 5-HT, was first identified in 1993. Over the course of the last 25 years, this receptor has been the subject of intense investigation, and it has been demonstrated that 5-HT plays an important role in a wide range of pharmacological processes.

Imidazo[1,2-a]pyrazine diaryl ureas: inhibitors of the receptor tyrosine kinase EphB4.

Inhibition of receptor tyrosine kinases (RTKs) such as vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs) has been validated by recently launched small molecules Sutent and Nexavar, both of which display activities against several angiogenesis-related RTKs. EphB4, a receptor tyrosine kinase (RTK) involved in the processes of embryogenesis and angiogenesis, has been shown to be aberrantly up regulated in many cancer types such as breast, lung, bladder and prostate. We propose that inhibition of EphB4 in addition to other validated RTKs would enhance the anti-angiogenic effect and ultimately result in more pronounced anti-cancer efficacy.

Synthetic Studies in Phytochrome Chemistry.

An account is given of the author's several approaches to the synthesis of the parent chromophore of phytochrome (1), a protein-bound linear tetrapyrrole derivative that controls photomorphogenesis in higher plants. These studies culminated in enantioselective syntheses of both 2R- and 2S-phytochromobilin (4), as well as several (13)C-labeled derivatives designed to probe the site of Z,E-isomerization during photoexcitation. When reacted in vitro, synthetic 2R-4 and recombinant-derived phytochrome apoprotein N-C produced a protein-bound chromophore with identical difference spectra to naturally occurring 1.

Privileged structures: applications in drug discovery.

Over the past 15 years the privileged structure concept has emerged as a fruitful approach to the discovery of novel biologically active molecules. Privileged structures are molecular scaffolds with versatile binding properties, such that a single scaffold is able to provide potent and selective ligands for a range of different biological targets through modification of functional groups. In addition, privileged structures typically exhibit good drug-like properties, which in turn leads to more drug-like compound libraries and leads.

Size of azurophil lysosomes of human PMNs determined by stereological morphometry.

The most striking feature of polymorphonuclear leukocytes is the presence of the subcellular organelles known as lysosomes. The peroxidase positive azurophil (primary) lysosomes are generally described in textbooks and the journal literature as predominantly ellipsoidal and approximately 500 nm in size. However, there appears to be no discovery research in the literature establishing that value.

A new synthesis of chlorins.

A new synthesis of chlorins has been developed, based upon the acid-catalyzed condensation of dialdehydes AB with dipyrromethanes CD.

Enantioselective syntheses of (13)C-labeled (2R)- and (2S)-phytochromobilin dimethyl ester.

(2R)- and (2S)-phytochromobilin dimethyl ester have been prepared in enantiomerically pure form, specifically (13)C-labeled at C(10) or C(15).

New syntheses of the C,D-ring pyrromethenones of phytochrome and phycocyanin.

Pyrromethenone 7, the C,D-ring segment of phytochrome (Pr, 4), has been prepared in an efficient fashion employing three new strategies. Each of these has potential advantages for the synthesis of labeled material. Our first approach is related to the Gossauer synthesis, with the difference that strong alkali is avoided in the condensation of the C- and D-ring components 8 and 17.

Morphology of azurophil lysosomes in polymorphonuclear leukocytes from humans with rapidly progressive periodontitis.

Previous investigations have shown that subjects with rapidly progressive periodontitis (RPP), an early-onset aggressive form of periodontitis, have polymorphonuclear leukocytes (PMNs) with increased intracellular levels of beta-glucuronidase, a characteristic enzyme of azurophil lysosomes. The current study attempted to account for that increase. Ten healthy controls and 10 otherwise healthy subjects with RPP participated.

Implications of resource-ratio theory for oral microbial ecology.

The ability to compete for the limited nutrients available to the microorganisms of dental plaque is a strong ecological determinant of the structure of the subgingival ecosystem. This paper introduces a new concept from the field of ecology, resource-ratio theory, and applies it to the dynamics of microbial dental plaque with emphasis on the putative periodontal pathogens. Resource-ratio theory is a mechanistic theory of resource competition that utilizes pairs of growth-limiting nutrients in a stoichiometric fashion to predict zones of competitive dominance, exclusion, and coexistence for organisms competing for these resources.

Clinical evaluation of restored maxillary incisors: veneers vs. PFM crowns.

This cross-sectional study compared the periodontal health and clinical acceptability of maxillary incisors restored with porcelain veneers vs. porcelain-fused-to-metal crowns. The authors evaluated 60 patients, a total of 120 restorations, in groups according to the age of the restorations (zero to 60 months).

Increased intracellular levels of lysosomal beta-glucuronidase in peripheral blood PMNs from humans with rapidly progressive periodontitis.

Release of potent lysosomal enzymes by degranulation of polymorphonuclear leukocytes (PMNs) in host gingiva may contribute significantly to tissue destruction and the pathogenesis of periodontal disease. A pilot study established that peripheral blood PMNs from humans with rapidly progressive periodontitis (RPP) contained significantly increased amounts of intracellular lysosomal beta-glucuronidase as compared to healthy controls. This investigation gained insight into the question: are the increased levels of beta-glucuronidase in persons with RPP an a priori genetically determined PMN characteristic, or a reactive phenomenon induced by the periodontal disease process during granulopoiesis? Twelve healthy controls and twelve otherwise healthy individuals with RPP participated in a repeated measures design to T0 (initial, baseline), T1 (four weeks after disease control therapy), and T2 (two months later).

The effect of Nd:YAG laser exposure on root surfaces when used as an adjunct to root planing: an in vitro study.

The purpose of this study was to evaluate the effects of Nd:YAG laser treatment on root surfaces in vitro when used alone or in combination with conventional scaling and root planing. The study population consisted of 18 unerupted third molars, each with a 3 mm diameter treatment site outlined on the root surface. Three specimens were randomly assigned to each of 6 different treatment groups: 1) untreated control; 2) root planed only; 3) laser treated only using 1.

The effects of the Nd:YAG laser on in vitro fibroblast attachment to endotoxin-treated root surfaces.

The purpose of this study was to evaluate the effects of the Nd:YAG laser on in vitro fibroblast attachment to endotoxin-treated root surfaces and to describe any laser-induced cementum surface alterations. Thirty 4 mm x 4 mm cementum segments were obtained from unerupted third molars. The treatment groups were as follows: 1) control, healthy root segment; 2) non-lased, endotoxin treated; and 3) lased, endotoxin treated.

Interrater agreement on subgingival calculus detection following scaling.

Accurate and reliable detection of subgingival calculus is a difficult skill which relies on subjective tactile sensations for determinations. This one year retrospective study examined the interrater agreement among a large, generalized pool of clinical examiners who scored residual subgingival calculus after student scaling. Four thousand one hundred and sixty tooth surfaces were analyzed for examiner agreement.

Fate of pocket epithelium in an apically positioned flap.

The fate of periodontal pocket epithelium when sulcular incisions are used in apically positioned flap surgery was investigated by serial histology. Human subjects received apically positioned flap segments on the facial aspect of anterior teeth timed to give 1, 3, 5, 7, 21 and 35 days of healing on the day of extraction. Companion surgeries for comparison consisted of similar flaps, but utilized an inverse bevel primary incision.

Increased intracellular levels of beta-glucuronidase in polymorphonuclear leucocytes from humans with rapidly progressive periodontitis.

The tissue destruction resulting from release of lysosomal enzymes by exocytosis and degranulation of polymorphonuclear leucocytes in host gingiva may contribute significantly to periodontal diseases. In this investigation peripheral blood was obtained from healthy controls and otherwise healthy individuals with rapidly progressive periodontitis. Polymorphonuclear leucocytes were isolated and suspended in HBSS for subsequent in vitro FMLP challenge to induce degranulation.

Assessment of curette sharpness.

Nothing to date has appeared in the literature addressing the relationship of specific bevel dimension and clinical sharpness of curette blades. This study investigated the degree of clinical sharpness of Gracey curettes following four periods of simulated root planning and, using the scanning electron microscope (SEM), determined the approximate number of strokes at which loss of clinical sharpness became apparent. Seventy-five new stainless steel curette blades were standardized and randomly assigned to one of five groups: control, 30-stroke, 50-stroke, 70-stroke, and 90-stroke.

Effects of an air-powder abrasive device used during periodontal flap surgery in dogs.

An air-powder abrasive system, the Prophy-Jet, is a commercially available product product intended for use during dental prophylaxis procedures. The purpose of this investigation was to assess the effects on periodontal tissues when the device is used as an adjunct to hand instrumentation in root preparation during periodontal surgery. The degree of tissue injury was assessed by evaluating clinical healing and by histometric analysis of the intensity of the inflammatory response at selected healing times.

Efficacy of face masks in preventing inhalation of airborne contaminants.

Use of surgical face masks has been advocated to protect clinicians from inhalation of aerosols containing organic and inorganic particulates. This study examined the ability of a 22 micron tracer particle to bypass the filtering capability of face mask material by peripheral marginal leakage of inspired air. For two popularly used face masks taped to a facial moulage, recovery of the tracer particle by an in vitro system was very low.