The impact of implant abutment surface treatment with TiO2 on peri-implant levels of angiogenesis and bone-related markers: a randomized clinical trial.

The goal of this randomized, blinded, split-mouth controlled clinical trial was to assess the influence of abutment surface treatment on tissue healing. Fifteen patients received two implants distributed randomly to two groups: test (TiO2 abutment surface), control (standard abutment surface). Levels of epidermal growth factor (EGF), bone morphogenetic protein 9 (BMP-9), endothelin 1 (ET-1), fibroblast growth factor (FGF), placental growth factor (PlGF), and vascular endothelial growth factor (VEGF) were quantified in the peri-implant fluid after 3, 14, 30, and 60 days. Inter-group comparisons indicated higher levels of EGF, BMP-9, ET-1, FGF, and PlGF in the test group after 30days (P<0.05). PlGF levels were also higher in the test group after 60 days. In the test group, intra-group analysis revealed different levels of ET-1 and FGF between days 3 and 30, and days 3 and 60 (P<0.05); furthermore, VEGF levels were significantly higher on day 60 than on day 3 (P <0.05). In the control group, intra-group analysis demonstrated significantly different levels of ET-1, FGF, and PlGF between days 3 and 60 and of PlGF between days 14 and 60 (P<0.05). In conclusion, abutment surfaces treated with TiO2 influenced the levels of angiogenesis and bone-related markers.

[Comparison of inhibitory effects of three natriuretic peptides on the proliferation of pulmonary artery smooth muscle cells of rats].

The inhibitory effects of atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP) and vasonatrin peptide (VNP) on the proliferation of pulmonary artery smooth muscle cells (PASMCs) were compared in rats. Total protein and OD value of MTT were detected in cultured rat PASMCs to examine the influence of the three peptides on PASMC proliforation induced by phorbol 12-myristate 13-acetate (PMA). The results show that PMA (10( 9) 10( 7) mol/L) increased and VNP (10( 8) 10( 6) mol/L), ANP and CNP (10( 7) 10( 6) mol/L) decreased the total protein and OD value in a dose-dependent manner (P<0.05). The data above suggest that PMA stimulates the proliferation of PASMCs while the three peptides inhibit the proliferation induced by PMA. Of the three peptides VNP has the strongest inhibitory effect.

[Comparison of vasorelaxing actions of vasonatrin peptide, C-type natriuretic peptide and atrial natriuretic peptide].

The vasorelaxing effects of vasonatrin peptide (VNP), C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP) on isolated rat pulmonary artery, abdominal aorta and celiac vein were measured by in vitro perfusion. The results showed that VNP, CNP and ANP caused concentration-dependent relaxation in isolated rat pulmonary artery, abdominal aorta and celiac vein with endothelium or without endothelium. The maximal responses (Rmax) of VNP were (76 +/- 17)%, (51 +/- 14)% and (62 +/- 14)% in pulmonary artery, abdominal aorta and celiac vein with endothelium respectively, whereas those of CNP were (31 +/- 8)%, (22 +/- 7)% and (41 +/- 8)%, and ANP (38 +/- 10)%, (41 +/- 10)% and (11 +/- 4)%. The median effective concentration (EC50) of VNP were 16 +/- 11, 35 +/- 18 and 12 +/- 8 nmol/L in pulmonary artery, abdominal aorta and celiac vein with endothelium respectively, while those of CNP were 148 +/- 112, 299 +/- 84 and 14 +/- 12 nmol/L, and ANP 66 +/- 47, 16 +/- 15 and 909 +/- 445 nmol/L. VNP were more effective than CNP and ANP, and the differences were statistically significant (P < 0.05-0.01). The potency of these peptides for relaxing the blood vessels can be summarized as: VNP > ANP > or = CNP for pulmonary artery; VNP > ANP > CNP for abdominal aorta; VNP > CNP > ANP for celiac vein. There was no significant difference between vessels with intact endothelium and those denuded of endothelium (P > 0.05).

Functional analyses of troponin T mutations that cause hypertrophic cardiomyopathy: insights into disease pathogenesis and troponin function.

Mutations in a number of cardiac sarcomeric protein genes cause hypertrophic cardiomyopathy (HCM). Previous findings indicate that HCM-causing mutations associated with a truncated cardiac troponin T (TnT) and missense mutations in the beta-myosin heavy chain share abnormalities in common, acting as dominant negative alleles that impair contractile performance. In contrast, Lin et al. [Lin, D., Bobkova, A., Homsher, E. & Tobacman, L. S. (1996) J. Clin. Invest. 97, 2842-2848] characterized a TnT point mutation (Ile79Asn) and concluded that it might lead to hypercontractility and, thus, potentially a different mechanism for HCM pathogenesis. In this study, three HCM-causing cardiac TnT mutations (Ile79Asn, Arg92Gln, and DeltaGlu160) were studied in a myotube expression system. Functional studies of wild-type and mutant transfected myotubes revealed that all three mutants decreased the calcium sensitivity of force production and that the two missense mutations (Ile79Asn and Arg92Gln) increased the unloaded shortening velocity nearly 2-fold. The data demonstrate that TnT can alter the rate of myosin cross-bridge detachment, and thus the troponin complex plays a greater role in modulating muscle contractile performance than was recognized previously. Furthermore, these data suggest that these TnT mutations may cause disease via an increased energetic load on the heart. This would represent a second paradigm for HCM pathogenesis.

Action of substance P and interaction of calcitonin gene-related peptide and substance P on the cat antral circular muscle.

The actions of substance P (SP) and calcitonin gene-related peptide (CGRP) and their interaction were examined in vitro in the feline antrum and colon. Circular muscle contraction was seen in the antrum to both peptides, but only to SP in the proximal colon. Antral contraction was enhanced when both peptides were given together. This interaction was inhibited by tetrodotoxin or atropine. SP acted at the antrum via a smooth muscle neurokinin receptor which is not a (NK)-1 receptor. SP binding was displaced by neurokinin A but not by the NK-1 receptor antagonist, CP-96345. The colonic response was inhibited by CP-96345. Immunohistochemistry revealed SP-like immunoreactivity (SP-LI) in fibers in the antral myenteric plexus and circular muscle, while CGRP-like immunoreactivity (CGRP-LI) was seen in the myenteric plexus only, without co-localization. These studies supported the hypothesis that SP acted via the NK-2 receptor at the feline circular muscle in the antrum to induce contraction and at the NK-1 receptor in the proximal colon. CGRP enhanced the effect of SP via a cholinergic pathway.

Expression and functional assessment of a truncated cardiac troponin T that causes hypertrophic cardiomyopathy. Evidence for a dominant negative action.

Mutations in the beta-myosin heavy chain gene are believed to cause hypertrophic cardiomyopathy (HCM) by acting as dominant negative alleles. In contrast, a truncated cardiac troponin T (TnT) that causes HCM implies that altered stoichiometry of contractile proteins may also cause cardiac hypertrophy. Wild-type and HCM-mutant (truncated) TnT were studied in a novel quail myotube expression system. Unexpectedly, antibody staining demonstrated incorporation of both forms of human cardiac TnT into the sarcomeres of quail myotubes. Functional studies of wild type and mutant transfected myotubes of normal appearance revealed that calcium-activated force of contraction was normal upon incorporation of wild type TnT, but greatly diminished for the mutant TnT. These findings indicate that HCM-causing mutations in TnT and beta-myosin heavy chain share abnormalities in common, acting as dominant negative alleles that impair contractile performance. This diminished force output is the likely stimulus for hypertrophy in the human heart.

[Correlation of intra-erythrocytic Na, K, Ca, Mg contents and ATPase activity with dilated cardiomyopathy].

Intra-erythrocytic contents of Na, K, Ca, Mg and activities of Na-K-ATPase (Na-pump) and Ca-Mg-ATPase (Ca-pump) were measured in 30 cases of dilated cardiomyopathy (DCM). Effects of treatment on these variables were simultaneously observed. The results showed that intra-erythrocytic Na, Ca contents increased and K, Mg contents decreased. That erythrocyte membrane Na-pump and Ca-pump were remarkably lower in DCM than those in the controls. Red cell cations and ATPase activities returned to normal following the recovery of cardiac function. It is suggested that abnormalities of intracellular cations and cell membrane cation transfer may play an important role in the mechanism of DCM.

Gastric effects of thyrotropin-releasing hormone microinjected into the dorsal vagal nucleus in cats.

We investigated the gastric acid secretory and motility responses to microinjection of thyrotropin-releasing hormone (TRH) into the dorsal motor nucleus of the vagus (DMV) in anesthetized cats. Gastric acid output was collected every 15 min through a gastric cannula after saline flush and titrated to pH 7.0. Antral and corpus contractions were continuously recorded by extraluminal force transducers. TRH dissolved in 200 nl of saline and microinjected unilaterally into the DMV induced a dose-dependent (50-200 ng) increase in gastric acid secretion. The acid secretory response began in the first 15 min collection and lasted 45 min. TRH frequently increased the force of contractions of the antrum and corpus within one minute of microinjection. The minimal effective dose for eliciting increased motility was lower than for inducing acid secretion. These results demonstrate that TRH acts in the DMV of cats to stimulate gastric acid secretion and contractions.

Gastric effects of TRH analogue and bicuculline injected into dorsal motor vagal nucleus in cats.

We investigated the gastric acid secretory and motility responses to microinjection into the dorsal motor nucleus of the vagus (DMV) of RX 77368, a stable thyrotropin-releasing hormone (TRH) analogue, and bicuculline, a gamma-aminobutyric acid (GABAA) receptor antagonist in ketamine-chloralose-anesthetized cats. Gastric acid output was collected every 15 min through a gastric cannula after saline flush and titrated to pH 7.0. Antral contractions were continuously recorded by an extraluminal strain gauge force transducer. The chemicals were dissolved in saline and unilaterally microinjected in volumes of 200 nl. RX 77368 or bicuculline microinjected into the DMV induced significant dose-dependent (50-500 ng) increases in gastric acid secretion and significant dose-dependent (50-200 ng) increases in the force of antral contractions. In response to both chemicals the gastric acid output increased in the first 15 min and peaked in the second and third collections. RX 77368 (500 ng) had a second greater peak 90 min after microinjection. The motility responses were rapid in onset and lasted 60 min for RX 77368 and 30 min for bicuculline. The minimal effective dose for eliciting increased motility was consistently lower than inducing acid secretion. Electrical stimulation of the DMV with 100 microA, 50-Hz, and 0.2-ms pulse duration increased the force of antral contractions but had no effect on gastric acid secretion. Our results demonstrate that the DMV exerts important control over both gastric acid secretion and motility in cats. TRH exerts a stimulatory influence, while GABAA receptors mediate an inhibitory influence on this vagal control.

Lateral hypothalamic sites in cats for stimulation of gastric antral contractions.

Electrical stimulation through a bipolar electrode introduced into either the left or right lateral hypothalamus of anesthetized cats by means of a stereotaxic instrument elicited stimulus-bound phasic antral contractions in the anesthetized cat's stomach of much greater force than recorded under basal conditions. There was no change in gastric acid output. The response was abolished by bilateral cervical vagotomy or atropine. Stimulation during an intravenous infusion of pentagastrin did not alter the gastric acid secretory response. A hypothalamic vagal and cholinergic excitatory gastric antral motor pathway to the stomach has been demonstrated, independent of an acid secretory response.