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Biomedical subjects

I Darby

Publications and source records attributed to I Darby.

8 recordsLinked to original sources
PubMed2003

Impaired nitric oxide function in the basilar artery of the obese Zucker rat.

The effect of insulin-resistance syndrome on vascular function has been examined in isolated basilar arteries using the obese Zucker rat (OZR) and age-matched lean littermate controls (lean Zucker rat; LZR) at 36 weeks of age. The OZR showed significantly reduced oral glucose tolerance and increased body weight, blood pressure, proteinuria, plasma levels of triglycerides, cholesterol, and insulin compared with the LZR. The contractile response to serotonin was significantly increased in the OZR. Furthermore, contractions to serotonin in LZR but not OZR were enhanced in the presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (NAME). Relaxations to acetylcholine (ACh), histamine, and A23187 were significantly reduced in precontracted arteries from the OZR. In the presence of NAME, histamine responses were significantly reduced whereas ACh and A23187 responses were almost abolished. Relaxations to free-radical nitric oxide (NO) and papaverine were not different in arteries from the OZR, even though responses to sodium nitroprusside were reduced in the OZR. Western blot and immunofluorescent quantitative analyses of eNOS content in cerebral microvessel fractions and basilar artery preparations, respectively, were not significantly different between OZR and LZR. The results suggest impairment in endothelial function resulting in reduced NO function in the basilar artery from the OZR.

Acetylcholine↗
PubMed2003

Dental implants: maintenance, care and treatment of peri-implant infection.

Osseointegration is becoming increasingly routine in the rehabilitation of partially or fully edentulous patients. However, the surrounding tissues may be subject to inflammatory conditions similar to periodontal disease and so require maintenance. This article discusses the background, aetiology, diagnosis of peri-implant diseases, and the maintenance, care and treatment of peri-implant infection in osseointegrated implants. Three case studies are presented to illustrate points in the care of implants.

Adult↗
PubMed2000

The cross-link breaker, N-phenacylthiazolium bromide prevents vascular advanced glycation end-product accumulation.

AIMS/HYPOTHESIS: Advanced glycation is postulated to have a pivotal role in mediating diabetic vascular complications. The emergence of thiazolium compounds such as N-phenacylthiazolium bromide which cleave preformed advanced glycation end products (AGEs) has allowed us to explore the effects of these agents on the vascular AGE accumulation and hypertrophy associated with diabetes. METHODS: Control and streptozotocin diabetic rats were selected at random for no treatment or treatment with N-phenacylthiazolium bromide (10 mg/kg intraperitoneally) and followed for 3 weeks. In a separate study, intervention with N-phenacylthiazolium bromide was delayed until after 3 weeks of diabetes and then given for 3 weeks (total of 6 weeks). RESULTS: Diabetes was associated with increased mesenteric vascular advanced glycation end products, as assessed by radioimmunoassay and immunohistochemistry. This increase in vascular AGE accumulation was prevented by N-phenacylthiazolium bromide treatment. Diabetes-associated mesenteric vascular hypertrophy was attenuated by treatment with N-phenacylthiazolium bromide only if given from the time of induction of diabetes. CONCLUSION/INTERPRETATION: Cross-link breakers seem to be effective in preventing or reversing accumulation of advanced glycation end-products in blood vessels and have the potential to play a part in the treatment of diabetic vascular complications.

Animals↗
PubMed1997

Extracellular matrix deposition, lysyl oxidase expression, and myofibroblastic differentiation during the initial stages of cholestatic fibrosis in the rat.

Early studies showed that during hepatic fibrosis induced by bile duct ligation, fibroblasts within the portal tracts proliferate and express alpha-smooth muscle (SM) actin, suggesting that they may be involved in the deposition of extracellular matrix components in cholestatic fibrosis. Thus, we investigated the deposition of extracellular matrix components (laminin, fibronectin EIIIA, collagen I and IV, procollagen III, elastin, tenascin) as well as the expression of lysyl oxidase and of alpha-SM actin in the portal zone at 24, 48, and 72 hours and 7 days after ligation of the common bile duct. Rat liver tissues were processed for immunofluorescence, in situ hybridization, immunohistochemistry, and for electron and immunoelectron microscopy. At all times examined after bile duct ligation, laminin was observed essentially in the basal membrane of vessels and portal ductules. In sham-operated animals, the fibronectin EIIIA was present exclusively in vessels; at 24 hours postinjury, fibronectin EIIIA expression appeared in both the portal zone and along sinusoids. Two days after ligation, increased expressions of collagen I and IV, procollagen III, and elastin were observed within the portal zone, compared with sham-operated animals. The deposition of these components increased thereafter. Tenascin expression increased soon after bile duct ligation in stroma surrounding proliferating ductules, reaching a maximum at 48 hours; thereafter, expression was restricted to the periphery of proliferating ductules. By in situ hybridization, procollagen I and tissue inhibitor of metalloproteinase-1 mRNA expression was greatly increased in periductular areas at 24 hours postligation and remained elevated throughout the experiment. At 24 hours, a strong reactivity for lysyl oxidase appeared in the portal zone, and, as in controls, alpha-SM actin expression was restricted to vascular SM cells. In the stroma adjacent to proliferating ductules, alpha-SM actin appeared at 48 hours, and the number of alpha-SM actin-positive cells increased until the 7th day. Lysyl oxidase staining increased until 72 hours after bile duct ligation, when it was located in areas surrounding the myofibroblastic cells. At 7 days, lysyl oxidase expression was restricted around myofibroblastic cells present at the periphery of the reactive tissue and appeared to extend into the surrounding parenchyma. These results show that after bile duct ligation, extracellular matrix deposition, and lysyl oxidase expression occur very early in portal connective tissue surrounding proliferating ductules, and precede myofibroblastic differentiation, ie, alpha-SM actin expression. In addition, the data are compatible with the suggestion that in the bile duct ligation model, myofibroblastic differentiation represents an adaptive response to modification of the extracellular matrix environment.

Actins↗
PubMed1995

Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar.

Granulation tissue formation and contraction is an important step of second intention wound healing. Granulation tissue develops from the connective tissue surrounding the damaged or missing area and its cellular components are mainly small vessel and inflammatory cells as well as fibroblasts and myofibroblasts. As the wound closes and evolves into a scar, there is an important decrease in cellularity; in particular myofibroblasts disappear. The question arises as to which process is responsible for this cellular loss. During a previous investigation on the expression of alpha-smooth muscle actin in myofibroblasts (Darby I, Skalli O, Gabbiani G, Lab Invest, 1990, 63:21-29), we have observed that in late phases of wound healing, many myofibroblasts show changes compatible with apoptosis and suggested that this type of cell death could be responsible for the disappearance of myofibroblasts. We have now tested this hypothesis by means of morphometry at the electron microscopic level and by in situ end labeling of fragmented DNA. Our results indicate that the number of myofibroblastic and vascular cells undergoing apoptosis increases as the wound closes and support the assumption that this is the mechanism of granulation tissue evolution into a scar. The regulation of apoptotic phenomena during wound healing may be important in scar establishment and development of pathological scarring.

Animals↗
PubMed1990

Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing.

We have studied the expression of alpha-smooth muscle actin, smooth muscle myosin, and desmin in granulation tissue during the healing of an open wound in the rat by means of electron microscopy and immunohistochemistry, at the light and electron microscopic levels, using specific antibodies directed against these proteins. Important amounts of the three antigens were always expressed in pericytic and/or smooth muscle cells of neoformed small vessels. In fibroblastic cells, microfilaments were absent 4 days after wounding but accumulated gradually, starting from the 6th up to the 15th day; at this time, they were evident in about 70% of fibroblastic cells (myofibroblasts). They then regressed progressively, and on the 30th day, microfilaments were no longer present in scar fibroblasts. alpha-Smooth muscle actin, but not smooth muscle myosin and desmin, was always present in microfilament bundles of myofibroblasts. The staining intensity was progressive from the 6th to the 15th day and decreased thereafter; no staining was seen at the 30th day. Between the 20th and the 25th day, many apoptotic figures were seen in fibroblastic and endothelial cells, suggesting that apoptosis is the mechanism of their disappearance. We conclude that myofibroblasts develop gradually from granulation tissue fibroblasts and temporarily express a marker of smooth muscle differentiation. These results may be relevant for the understanding of the mechanisms of normal and pathologic wound healing.

Actins↗
PubMed1989

Inhibition of angiotensinogen production by angiotensin II analogues in human hepatoma cell line.

The aim of this study was to examine in Hep G2, a human hepatoma-derived cell line, the presence of angiotensin II (ANG II) receptors and the effect of ANG II and its analogues on angiotensinogen production. The presence of ANG II receptors was demonstrated using a long-acting ANG II analogue, 125I-labeled [Sar1]ANG II. A single class of specific binding sites was identified in these cells with a dissociation constant (Kd) of 2 nM. The number and affinity of these binding sites were not changed by [Sar1]ANG II treatment over 24 h. ANG II showed an inhibitory effect on angiotensinogen production. [Sar1]ANG II also exhibited a similar inhibitory effect as that of ANG II but to a greater extent and therefore was used throughout these studies. [Sar1]ANG II inhibited angiotensinogen production in a dose-dependent manner, exhibiting a half-maximal inhibitory concentration (IC50) of 2 nM. Other ANG II analogues showed similar effects on angiotensinogen production. In order of decreasing ability, they were [Sar1]ANG II greater than [Sar1-Ala8]ANG II greater than [Sar1-Val8]ANG II greater than [Sar1-Val5-(Br5)-Phe8]ANG II greater than [Sar1-Val5-DPhe8]ANG II. Results of these studies show that the Hep G2 cell possesses specific ANG II receptors and that [Sar1]ANG II induces a dose-dependent inhibition of angiotensinogen production in this system.

Angiotensin II↗