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1.
Int J Mol Med ; 35(4): 1088-94, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25716282

ABSTRACT

Evidence has been accumulating for a role for metformin in reducing breast cancer risk in post-menopausal women. It inhibits growth of breast cancer cells via several mechanisms, primarily the AMPK/mTOR signalling pathway. Another possible protective mechanism may be the ability of metformin to inhibit aromatase activity. In the present study, we investigated the effects of metformin on the basal growth of MCF-7 cells, after oestradiol (E2) stimulation and after the inhibition of mTOR by rapamycin. Secondly, we investigated the effects of metformin on the activity of a number of steroidogenic enzymes and the mRNA expression of aromatase and steroid sulphatase (STS). High doses of metformin significantly inhibited both basal and oestrogen-stimulated cell division. Low-dose rapamycin (10-10 M) did not inhibit growth, but the addition of metformin induced a significant reduction in growth. High-dose rapamycin (10-8 M) inhibited growth, and this was further attenuated by the addition of metformin. Exposure to low (10-7 M) and high (10-4 M) doses of metformin for 7-10 days significantly reduced the conversion of androstenedione (ANDRO) and testosterone (TESTO) (both requiring aromatase), but not the conversion of oestrone or oestrone sulphate (ES) via 17ß-hydroxysteroid dehydrogenase/sulphatase to E2. This attenuation was via a downregulation in the expression of total aromatase mRNA and promoter II, whilst the expression of sulphatase was unaffected by metformin. In conclusion, plasma levels of metformin have a dual therapeutic action, first by directly inhibiting cell proliferation which can be augmented by rapamycin analogues, and secondly, by inhibiting aromatase activity and reducing the local conversion of androgens to E2.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/metabolism , Estradiol/biosynthesis , Metformin/pharmacology , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Estradiol/pharmacology , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , MCF-7 Cells , Sirolimus/pharmacology
2.
Reproduction ; 136(2): 187-94, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18456904

ABSTRACT

Histological studies have demonstrated that polycystic ovaries (PCO) contain increased numbers of preantral follicles with a specific increase in primary follicles. Polycystic ovary syndrome is associated with hyperandrogenism and pre- and postnatal androgenization of primates increases the pool of growing follicles producing changes resembling PCO. In vitro studies could test the hypothesis that androgens alter early folliculogenesis, but conventional culture techniques for small follicles are generally unsuitable in non-rodent species. Our objective was to develop and use a method to investigate the effects of testosterone on early folliculogenesis. We adapted an in ovo technique in which lamb cortical ovarian fragments were grafted onto the chorioallantoic membrane of fertilised chick eggs. Optimal experimental conditions for vascularisation and survival of tissue were determined and the model then used to investigate the effects of testosterone on follicle growth. Eggs were inoculated with testosterone at the time of implantation of the ovarian tissue, which was retrieved 5 days later. Tissue was sectioned and follicles staged and counted. There was no wholesale initiation of primordial follicle growth over the 5-day in ovo culture. Importantly, the proportion of primordial, primary and secondary follicles remained similar to those in unimplanted tissue. Testosterone increased the number of primary follicles by 50% compared with controls, an effect that was largely due to a reduction in atresia. In conclusion, incubation of ovarian cortex with testosterone reproduces the changes in early folliculogenesis reported in histological studies of PCO.


Subject(s)
Ovarian Follicle/drug effects , Polycystic Ovary Syndrome/metabolism , Testosterone/pharmacology , Animals , Chick Embryo , Chorioallantoic Membrane/metabolism , Female , Follicular Atresia/drug effects , Models, Animal , Ovary/metabolism , Ovary/transplantation , Ovum , Sheep , Stimulation, Chemical , Transplantation, Heterologous
3.
Hum Reprod ; 18(3): 487-94, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12615812

ABSTRACT

BACKGROUND: Studies using purified enzyme preparations, placental microsomes or cell lines have shown that certain phytoestrogens can inhibit the enzymes that convert androgens to estrogens, namely aromatase and 17beta-hydroxysteroid dehydrogenase (HSD) type 1 and type 5. The study aim was to investigate the effects of selected phytoestrogens on aromatase and 17beta-HSD type 1 activity in primary cultures of human granulosa-luteal (GL) cells. METHODS AND RESULTS: GL cells, cultured for 48 h in medium containing 5% fetal calf serum and for a further 24 h in serum-free medium with or without hFSH or hCG, were exposed to steroid substrates during the last 1-4 h of the experiment. The production of progesterone in the presence of pregnenolone or estradiol synthesis from androstenedione, estrone or testosterone showed dose- and time-dependent increases. Whilst hCG priming had no effect on progesterone production, FSH priming induced mean 68 and 56% increases in the production of estradiol from androstenedione (A-dione) and estrone respectively, but had no significant effect on the metabolism of testosterone to estradiol. None of the phytoestrogens investigated had any acute effects on enzyme activity. In contrast, when GL cells were exposed to the compounds for 24 h prior to exposure to steroid substrates for 4 h, 10 micro mol/l apigenin and zearalenone significantly inhibited aromatase activity, whilst biochanin A and quercetin had no effect. None of the phytoestrogens inhibited FSH-induced 17beta-HSD type 1 activity, and only quercetin significantly inhibited progesterone production. CONCLUSIONS: The inability of phytoestrogens to acutely inhibit steroidogenic enzymes in human GL cells (as has been shown in cell-free models) suggests that they are either rapidly metabolized to relatively inactive compounds or that the high enzyme activity in human GL cells masks any inhibitory effects of the compounds at the concentration tested.


Subject(s)
17-Hydroxysteroid Dehydrogenases/metabolism , Aromatase Inhibitors , Corpus Luteum/enzymology , Enzyme Inhibitors/pharmacology , Estrogens, Non-Steroidal/pharmacology , Follicle Stimulating Hormone/pharmacology , Granulosa Cells/enzymology , Isoflavones , Zeranol/analogs & derivatives , Apigenin , Cells, Cultured , Corpus Luteum/cytology , Enzyme Induction , Female , Flavonoids/pharmacology , Genistein/pharmacology , Humans , Phytoestrogens , Plant Preparations , Quercetin/pharmacology , Zeranol/pharmacology
4.
Br Dent J ; 191(8): 421-4, 427-30, 433-4, 2001 Oct 27.
Article in English | MEDLINE | ID: mdl-11720016

ABSTRACT

In most patients the existing occlusal scheme will be functional, comfortable and cosmetic; and so if a tooth or teeth need to be restored, the most appropriate way to provide the restoration(s) would be to adopt a 'conformative' approach: that is to provide treatment within the existing envelope of static and dynamic occlusal relationships. There will, however, be situations where the conformative approach cannot be adopted, and this section aims to describe what is 'Good Occlusal Practice' in these circumstances.


Subject(s)
Denture Design , Malocclusion/therapy , Occlusal Adjustment , Centric Relation , Dental Articulators , Humans , Jaw Relation Record , Models, Dental , Patient Care Planning
5.
Acta Physiol Scand ; 172(1): 17-25, 2001 May.
Article in English | MEDLINE | ID: mdl-11437736

ABSTRACT

Follicular atresia is associated with the presence of increased macrophages within the follicle. What is not known is whether, in the adult rat, macrophages are instrumental in inducing apoptosis and/or atresia or whether they are simply secondary to a hormonally mediated event. As prolactin is an immunoreactive hormone and stimulates the expression of monocyte chemoattractant, the present experiments compared the effects of prolactin treatment with that of an immune challenge with lipopolysaccharide (LPS) on the invasion of macrophages into the follicular and luteal compartments of the ovary and the occurrence of apoptosis/atresia in relation to macrophage invasion. Rats were treated for 3 days with either prolactin or LPS and ovaries obtained at pro-oestrus or oestrus. Prolactin and LPS increased the number of atretic vs. healthy follicles (P < 0.008, chi2) in pro-oestrus ovaries and increased the mean number of apoptotic cells and macrophages (P < 0.05 for some groups). Macrophages were typically observed in the thecal layer, apoptotic cells in the granulosa cell layer, although 84% follicles which had macrophages within the granulosa cell layer also contained relatively high numbers of apoptotic nuclei. Prolactin and LPS treatment in vivo reduced the progesterone response to follicle stimulating hormone (FSH) (P < 0.001) in cultures of ovarian dispersates but did not inhibit the response to forskolin. In contrast, prolactin or LPS added in vitro to the cultures inhibited the progesterone response to forskolin. Results show that both prolactin and LPS increase follicular apoptosis and atresia and reduce the progesterone response to FSH.


Subject(s)
Apoptosis/drug effects , Escherichia coli , Follicular Atresia/drug effects , Lipopolysaccharides/pharmacology , Ovarian Follicle/drug effects , Prolactin/pharmacology , Animals , Cell Count , Cell Survival/drug effects , Cells, Cultured , Culture Media, Conditioned/chemistry , Female , Follicular Atresia/immunology , Immunohistochemistry , In Situ Nick-End Labeling , Macrophages/drug effects , Macrophages/immunology , Macrophages/pathology , Ovarian Follicle/immunology , Ovarian Follicle/metabolism , Ovarian Follicle/pathology , Ovary/cytology , Ovary/drug effects , Progesterone/metabolism , Rats , Rats, Wistar
6.
Exp Biol Med (Maywood) ; 226(6): 570-6, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11395928

ABSTRACT

Previous studies have shown that the phytoestrogen, genistein, inhibits basal and forskolin-stimulated progesterone synthesis in rat granulosa-luteal cells. Genistein, however, not only binds and activates the estrogen receptor (ER), but is also a potent inhibitor of tyrosine kinase. In these studies we have compared the effects of estradiol, two other phytoestrogens, apigenin and coumarin, the pesticide, [2-(chlorphenyl)-2-(4-chlorphenyl)-1,1,1-trichlorethan] (2,4'DDT), and the industrial chemical, 4-octyl-phenol, on basal and follicle stimulating hormone (FSH)-stimulated progesterone production in the same experimental system. Only a supraphysiological dose of estradiol (10(-5) M) significantly inhibited basal and forskolin-stimulated progesterone production in granulosa-luteal cells, but had no effect on FSH-stimulated production. In contrast, apigenin, DDT, and octyl-phenol stimulated basal progesterone production at doses around 10(-8) to 10(-7) M, but this effect was reversed at higher doses. Coumarin was without effect. Like basal production, the two phytoestrogens had opposing effects on FSH-stimulated progesterone production. Genistein at 10(-5) M was inhibitory, while apigenin significantly potentiated the response at 19(-7) M. In contrast, DDT had no effect on the FSH-induced response, though 10(-7) M octyl-phenol nearly doubled the response. While all these chemicals are known to interact with the estrogen receptor to a greater or lesser extent, these studies suggest that like genistein, these different endocrine-disrupting chemicals may have other actions apart from those on the estrogen receptor.


Subject(s)
Estrogens/pharmacology , Follicle Stimulating Hormone/pharmacology , Granulosa Cells/drug effects , Progesterone/biosynthesis , Animals , Apigenin , Cells, Cultured , Colforsin/pharmacology , Coumarins/pharmacology , DDT/pharmacology , Estradiol/pharmacology , Female , Flavonoids/pharmacology , Genistein/pharmacology , Granulosa Cells/cytology , Granulosa Cells/metabolism , Phenols/pharmacology , Rats , Rats, Wistar
7.
J Reprod Fertil ; 118(1): 187-93, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10793641

ABSTRACT

Treatment of immature rats with 5 iu equine chorionic gonadotrophin (eCG) on day 25 typically stimulates a preovulatory surge of LH on day 27 and ovulation on day 28. In rats weighing > 60 g at the time of treatment, an LH surge and ovulation occurred in 75% of the animals but, in rats weighing < 60 g, only 13% ovulated even though 69% showed an LH surge. Previous findings have shown that exogenous LH can stimulate ovulation in the rats < 60 g, indicating that the anovulation was not due to ovarian immaturity, but rather to an abnormal form of LH. Thus, it was important to determine whether the bioactivity of LH released at the time of the surge differs in rats < 60 g compared with rats > 60 g. Experiments showed that LH from both groups of eCG-treated animals were equipotent in stimulating testosterone production from incubated Leydig cells and progesterone production from cultured granulosa cells. Similarly the surge of progesterone in vivo, which occurs co-incident with the LH surge, was of similar magnitude in both groups of animals. Since prostaglandin synthesis increases at the time of ovulation and is also stimulated by LH, it was investigated whether the activity of ovarian phospholipase A2, the rate limiting enzyme in prostaglandin synthesis, and ovarian prostaglandin E2 concentrations differed in the animals > 60 g and < 60 g. Phospholipase A2 activities were similar in both groups of animals at the time of the LH surge, as were the prostaglandin E2 concentrations. However, in all animals that ovulated (15/20 in rats > 60 g and 2/15 in rats < 60 g), there was a threefold increase in ovarian prostaglandin E2 concentrations. The results show that, in underweight animals, the bioactivity of LH, in terms of its ability to stimulate steroidogenesis and phospholipase A2 activity, is similar to that released by animals > 60 g; however, the LH produced by the underweight animals fails to induce ovulation by failing to increase, either directly or indirectly, prostaglandin E2 production. Comparison of the profiles of plasma LH collected at the time of the LH surge on an anionic ion exchange column indicates that the LH from rats < 60 g possesses significantly less of the neutral or basic glycoform of LH than that from rats > 60 g. This finding provides a further index that the biopotency of LH produced by underweight animals is different from that of rats > 60 g.


Subject(s)
Luteinizing Hormone/metabolism , Sexual Maturation/physiology , Animals , Biological Assay , Body Weight , Chromatography, Ion Exchange , Dinoprostone/metabolism , Female , Gonadotropins, Equine/pharmacology , Granulosa Cells/metabolism , Leydig Cells/drug effects , Leydig Cells/metabolism , Luteinizing Hormone/pharmacology , Male , Ovary/metabolism , Ovulation Induction , Phospholipases A/metabolism , Phospholipases A2 , Progesterone/biosynthesis , Rats , Rats, Wistar , Testosterone/biosynthesis
8.
Fertil Steril ; 73(3): 613-9, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10689022

ABSTRACT

OBJECTIVE: To compare the effects of two protein tyrosine kinase inhibitors, lavendustin A and the phytoestrogen genistein, on progesterone synthesis in cultured rat ovarian cells. DESIGN: Experimental animal study. SETTING: Medical school laboratory. ANIMAL(S): Porton Wistar rats. INTERVENTION(S): Ovaries from estrous rats were used to establish cell cultures of granulosa-luteal cells from freshly ruptured follicles, granulosa-luteal cells cocultured with peritoneal macrophages, and whole ovarian dispersates. MAIN OUTCOME MEASURE(S): Progesterone and nitrite concentrations in the culture medium. RESULT(S): The protein tyrosine kinase inhibitors suppressed steroid synthesis in a dose-dependent manner and completely inhibited the steroidogenic response to both FSH and the adenyl cyclase stimulator forskolin. The inhibitory action of cocultured macrophages on basal and forskolin-stimulated progesterone production in granulosa-luteal cells was not reversed by genistein, nor was the inhibitory effect of interleukin-1beta in cultures of ovarian dispersates. CONCLUSION(S): Genistein and the nonestrogenic protein tyrosine kinase inhibitor lavendustin A exert potent inhibitory effects on steroidogenesis that are independent of cytokines. The toxic effects of genistein on sexual development and reproduction may be attributed not only to its estrogenic action but also to its action as a protein tyrosine kinase inhibitor.


Subject(s)
Enzyme Inhibitors/pharmacology , Genistein/pharmacology , Ovary/metabolism , Phenols/pharmacology , Progesterone/biosynthesis , Protein-Tyrosine Kinases/antagonists & inhibitors , Animals , Cells, Cultured , Colforsin/pharmacology , Dose-Response Relationship, Drug , Female , Follicle Stimulating Hormone/pharmacology , Interleukin-1/pharmacology , Nitrites/metabolism , Ovary/cytology , Ovary/drug effects , Rats , Rats, Wistar
9.
J Esthet Dent ; 12(1): 38-45, 2000.
Article in English | MEDLINE | ID: mdl-11323832

ABSTRACT

PURPOSE: Porcelain veneers are a safe and effective treatment modality for selected teeth that have poor esthetics. However, removal of porcelain veneers that have failed may be time-consuming and involve considerable removal of sound tooth structure adjacent to the veneer. The aim of this study was to evaluate a novel method of porcelain laminate veneer removal by incorporating a fluorescent dye into the luting cement that allows the practitioner to visualize the cement on the tooth and remove the veneer without causing residual damage to the adjacent tooth substance. MATERIALS AND METHODS: Porcelain veneers were luted on extracted teeth with a luting cement modified with a fluorescing agent. Faculty teaching staff and final year dental undergraduates were asked to remove the veneers with the aid of a curing light to render the luting cement visible by fluorescing. They were then asked to compare the removal of comparable veneers without this visual aid and to complete a standard questionnaire. The depth of cure of the conventional and modified cements was measured using a penetrometer. RESULTS: Results of the questionnaire indicated that the operators found removing the veneer cemented with the modified (fluorescing) cement considerably easier than removing the veneer cemented with the conventional cement. Microscopy indicated that more damage was caused to the underlying tooth during removal of conventionally cemented veneers. The incorporation of the dye into the cement reduced the depth of cure from 4.238 mm (SD = 0.025) to 3.761 mm (SD = 0.096).


Subject(s)
Dental Debonding , Dental Veneers , Dental Porcelain , Fluorescent Dyes , Humans
10.
Dent Mater ; 15(2): 79-86, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10551099

ABSTRACT

OBJECTIVES: The purpose of this study was to evaluate and compare two "stylus" methods for measuring surface texture of dental tissues and materials. METHODS: The two styli chosen were a contact diamond stylus and a non-contact focussed laser stylus attached to the same measuring apparatus. RESULTS: These indicate that there are significant differences between those obtained from surface texture measurements using a non-contact laser stylus and a diamond contact stylus method despite being mounted in the same profilometer. This is valid for both the test specimens of known surface texture, provided by the manufacturers, and for a "real world" simulation using contoured and finished Dicor ceramic blocks. The only significant agreement between the two styli was found for the Ra parameter. This should not be used alone to describe the roughness of a surface because the parameter is not sensitive to profile shape. Owing to the properties of the stylus used it is essential that the limitations of surface profilometry be recognised. SIGNIFICANCE: Caution should be exercised when comparing the results of surface texture studies of dental hard tissues and restorative materials using varying types of stylus attached to a surface profilometer.


Subject(s)
Dental Equipment , Dental Polishing , Dental Porcelain , Materials Testing/instrumentation , Diamond , Lasers , Reproducibility of Results , Surface Properties
11.
Eur J Prosthodont Restor Dent ; 7(4): 131-4, 1999 Dec.
Article in English | MEDLINE | ID: mdl-11314426

ABSTRACT

The aim of this study was to demonstrate the extent of tooth flexure under axial loading using profilometry. Fifteen extracted human permanent upper premolar teeth were embedded in hard die stone and divided into 3 groups. One group was left unprepared, the second group had artificial cervical saucer shaped lesions prepared and the final group had artificial cervical notch lesions prepared. The labial profile was taken using a diamond stylus mounted in a Profilometer. The teeth were then loaded in an axial direction to circa 670 N and the labial surface re-profiled 20 s after loading. The results indicate that changes occur in the labial profile of premolar teeth that are subjected to axial loading which could be considered to represent vertical barrelling. Changes in the profile of the artificial saucer and notch lesions prepared at the cervical region suggest that stresses would be generated on restorations of these lesions.


Subject(s)
Bicuspid/physiopathology , Dental Stress Analysis/instrumentation , Tooth Cervix/pathology , Dental Restoration Failure , Humans , Maxilla , Pliability , Tooth Cervix/physiopathology
12.
J Esthet Dent ; 11(6): 332-7, 1999.
Article in English | MEDLINE | ID: mdl-10825868

ABSTRACT

PURPOSE: The initiation and progression of noncarious cervical notch lesions (NCCL) continues to perplex clinicians worldwide and poses a considerable restorative challenge. The purpose of this brief communication is to report what is believed to be the first in vitro production of notch-shaped lesions in the cervical third of premolar teeth. MATERIALS AND METHODS: The lesions, were produced by axial loading of selected permanent premolar teeth in a 10% aqueous solution of sulfuric acid over a period of 5 days, followed by immersion in water for 7 days. RESULTS: Results revealed macroscopic and microscopic features similar to those observed in noncarious cervical lesions in vivo. The lesions were incidental findings while the authors were studying stress corrosion of enamel at low pH. Although much remains to be investigated regarding the etiology and pathogenesis of NCCL, axial loading and a corrosive environment may be implicated in these processes. The artificial lesions arose in clinically sound teeth, suggesting that there is no simple clinical examination to identify teeth at risk from NCCL. CLINICAL SIGNIFICANCE: The relationship between the development of NCCL and applied stress indicates that occlusal factors may play the most significant role in the initiation and progression of NCCL.


Subject(s)
Tooth Abrasion/etiology , Tooth Cervix/pathology , Tooth Erosion/etiology , Bicuspid/pathology , Corrosion , Dental Stress Analysis , Humans , In Vitro Techniques , Microscopy, Electron, Scanning , Statistics, Nonparametric , Stress, Mechanical , Sulfuric Acids , Tooth Cervix/ultrastructure
13.
Eur J Endocrinol ; 137(3): 293-300, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9330595

ABSTRACT

It has been reported that interleukin (IL)-1 beta induces the synthesis of both nitric oxide (NO) and prostaglandin (PG)E2 in cultures of dispersed ovarian cells and exerts cytotoxic effects on these cells. Since PGE2, NO and IL-1 beta have been implicated as modulators of steroidogenesis, experiments have been undertaken to determine how IL-1 beta-induced NO and PGE2 production may affect steroidogenesis in cultures of ovarian dispersates obtained from untreated adult oestrous rats and to compare the action of IL-1 beta in cultures of granulosa/luteal (GL) cell-only cultures and GL cells co-cultured with peritoneal macrophages. IL-1 beta significantly increased the production of NO (assessed by nitrite measured in the culture medium) and PGE2 in cultures of ovarian dispersates but had no effect on cultures of GL cells in which NO production was typically very low and PGE2 production was undetectable. In contrast both NO and PGE2 were high in co-cultures and were not significantly altered by the addition of IL-1 beta. The NO donor sodium nitroprusside inhibited steroidogenesis in cultures of ovarian cells in a dose-dependent manner while PGE2 had a stimulatory effect. Concomitant inhibition of NO production with aminoguanidine and PG production with indomethacin resulted in a significant enhancement of basal progesterone production in these cultures. Finally, IL-1 beta inhibited progesterone responses to forskolin and PGE2 in ovarian dispersates: an effect not observed in GL cell-only cultures nor in co-cultures in which forskolin-induced progesterone production is always inhibited. No cytotoxic effects of IL-1 beta during the 48 h period of culture were observed. A comparison of the steroidogenic NO and PGE2 responses to IL-1 beta in the three culture models suggests that (i) the response to IL-1 beta observed in ovarian dispersates could be due to cytokine activation of resident and infiltrating macrophages or that the action of IL-1 beta requires some other heterologous cell-cell contact, and (ii) IL-1 beta acts indirectly on signal transduction pathways which stimulate steroidogenesis.


Subject(s)
Dinoprostone/pharmacology , Interleukin-1/pharmacology , Nitric Oxide/pharmacology , Ovary/metabolism , Steroids/biosynthesis , Animals , Cells, Cultured , Colforsin/pharmacology , Cyclooxygenase Inhibitors/pharmacology , Dinoprostone/biosynthesis , Drug Interactions , Enzyme Inhibitors/pharmacology , Female , Guanidines/pharmacology , Indomethacin/pharmacology , Nitric Oxide/biosynthesis , Nitric Oxide Synthase/antagonists & inhibitors , Nitroprusside/pharmacology , Ovary/drug effects , Rats , Rats, Wistar
14.
J Oral Rehabil ; 24(6): 449-53, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9219990

ABSTRACT

There are various methods of measuring tooth wear, including that which could be considered to be associated with acid erosion. However, the present systems are limited in that they require an extended period of study to detect wear and also they do not give any insight as to the underlying mechanism of the tooth tissue loss. The aim of this study was to use a profilometric measuring system analysing novel surface texture parameters normally associated with the automobile industry to describe the wear and run-in behaviour of machined sliding engine parts. The texture parameters selected were the traditional Ra parameter and also parameters derived from the bearing ratio. Analyses of the surface texture of the labial surface of upper central incisors at an interval of three months indicated that the enamel surface was smoother but there were subtle changes occurring to the enamel. There was a statistically significant increase in the depth of pits/pores of the enamel surface, which could be identified as sites of retention of exogenous acid or chelating agent. The effects of acid erosion are not uniform but are dependent upon several factors; the configuration of the enamel surface may play an important part in the mediation of acid erosion type lesions.


Subject(s)
Dental Enamel/pathology , Tooth Erosion/pathology , Adult , Dental Enamel/ultrastructure , Humans , Microscopy, Electron, Scanning , Replica Techniques , Surface Properties
15.
Eur J Endocrinol ; 136(3): 330-7, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9100560

ABSTRACT

There is increasing evidence that ovarian steroids inhibit vascular responsiveness to the neurohypophysial hormone vasopressin. The present study examined the recovery of the arterial blood pressure following a single (2 ml/100 g body weight) haemorrhage in ovariectomized (OVX) Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) and rats of the parent Long Evans (LE) strain. Some groups of OVX rats received subcutaneous implants of either 17 beta-oestradiol (E2) or progesterone 7 days prior to haemorrhage. The arterial blood pressure recovery immediately following haemorrhage was significantly impaired in both groups of steroid-treated OVX LE rats compared with the OVX controls (both comparisons P < 0.05). The impairment in blood pressure recovery seen in the steroid-replaced OVX LE rats was similar to that seen in pro-oestrous rats (when ovarian steroid levels are raised) compared with male rats of this strain (P < 0.05). In contrast, ovariectomy with or without steroid replacement in BDI rats had no further effect on the already attenuated recovery of arterial blood pressure after haemorrhage in this strain. Heart rate responses to haemorrhage also showed strain differences, which were dependent on steroid treatment. Pro-oestrous female LE rats showed a small decrease in heart rate after haemorrhage, followed by a recovery process, and this initial bradycardia was markedly enhanced in the OVX steroid-treated animals. In contrast, untreated OVX LE rats showed an initial and sustained increase in heart rate which was significantly higher than in the steroid-treated OVX animals (P < 0.05). All BDI rats, irrespective of treatment, consistently showed an increased heart rate after haemorrhage. In conclusion, ovarian steroid replacement in OVX LE, but not vasopressin-deficient BDI, rats was associated with an attenuated pressor recovery after haemorrhage. This provides further evidence for the existence of an important inhibitory interaction between ovarian steroids and vasopressin. The initial decrease in heart rate observed in pro-oestrous and steroid-treated OVX LE rats after haemorrhage also appears to be related to an ovarian steroid-vasopressin interaction.


Subject(s)
Blood Pressure/drug effects , Diabetes Insipidus/physiopathology , Estradiol/pharmacology , Hemorrhage/physiopathology , Ovariectomy , Progesterone/pharmacology , Rats, Brattleboro/physiology , Animals , Female , Heart Rate , Male , Rats , Rats, Inbred Strains , Rats, Mutant Strains , Vasopressins/deficiency
16.
Clin Sci (Lond) ; 92(3): 277-84, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9093008

ABSTRACT

1. A few studies have shown that nitric oxide may exert cytotoxic and/or steroidogenic effects on cultured ovarian cells but the source of this factor within the ovary remains equivocal. 2. In this study we have investigated the effects of nitric oxide on progesterone secretion, cell viability and cell morphology of cultured rat granulosa/lutein cells and examined whether granulosa cells are an important source of nitric oxide. 3. Only very low or undetectable levels of nitrites were measured in granulosa/lutein-cell-only cultures, although there was a small but significant increase in nitrite release observed in granulosa/ lutein cells obtained from oestrous rats compared with those obtained from proestrous rats. 4. There was a concentration-dependent inhibition of progesterone synthesis in the presence of the nitric oxide donors sodium nitroprusside and S-nitroso-N-acetyl-penicillamine which corresponded with an increased concentration of nitrite accumulation in the culture medium. 5. High concentrations of nitrites were measured in the medium of granulosa/lutein cells co-cultured with peritoneal macrophages and progesterone synthesis was inhibited. This effect of the macrophages was partially reversed by inhibitors of nitric oxide synthesis, aminoguanidine, NG-methyl-L-arginine and NG-L-arginine-methyl-ester, and the reversal of inhibition was inversely proportional to the concentration of nitrites measured in the medium. Dose-response curves for the three drugs on the inhibition of nitrite accumulation in macrophage cultures were obtained. 6. The nitric oxide scavenger c-PTIO [2-(4-carboxy-phenyl) -4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide.potassium salt] partially reversed the effects of S-nitroso-N-acetyl-penicillamine and macrophages on progesterone synthesis in granulosa/ lutein cells. 7. With the exception of the high dose of sodium nitroprusside, there was no evidence that any of the drugs reduced cellular viability, as assessed by measurement of cellular dehydrogenases and Trypan Blue exclusion, although high concentrations of nitrite in the culture medium derived either from the nitric oxide donors or macrophages were associated with a loss of morphological luteinization. 8. Based on the available evidence, we suggest that nitric oxide can inhibit steroidogenesis and that in vivo the source of nitric oxide may be from macrophages, which invade the ovary during the periovulatory period, and/or from endothelial cells of ovarian blood vessels.


Subject(s)
Granulosa Cells/metabolism , Nitric Oxide/physiology , Nitroprusside/pharmacology , Penicillamine/analogs & derivatives , Progesterone/biosynthesis , Vasodilator Agents/pharmacology , Animals , Arginine/analogs & derivatives , Arginine/pharmacology , Cells, Cultured , Coculture Techniques , Dose-Response Relationship, Drug , Female , Guanidines/pharmacology , Macrophages/metabolism , Nitric Oxide Synthase/antagonists & inhibitors , Nitrites/metabolism , Penicillamine/pharmacology , Rats , Rats, Wistar , S-Nitroso-N-Acetylpenicillamine , omega-N-Methylarginine/pharmacology
17.
Fertil Steril ; 66(3): 487-9, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8751755

ABSTRACT

OBJECTIVE: To compare the activity of peritoneal fluid (PF) from women with and without endometriosis or polycystic ovary syndrome (PCOS) on P release from cultured human granulosa-lutein cells. DESIGN: Case-control study. SETTING: Medical school and hospital. PATIENTS: Women with mild to moderate endometriosis or PCOS and controls undergoing laparoscopic sterilizations. MAIN OUTCOME MEASURES: Human granulosa-lutein cells, obtained from the IVF clinic, were cultured with increasing volumes of steroid-extracted PF samples with and without hCG. Progesterone concentrations in the media after 72 hours culture were measured by RIA. RESULTS: Peritoneal fluid stimulated P release in a dose-dependent manner and, at the highest dose, the response was enhanced significantly by PF from women with endometriosis and PCOS compared with control samples. The effects of PF plus hCG were not simply additive. There was a large potentiation of the response, which was greater in women with endometriosis and PCOS. CONCLUSIONS: Peritoneal fluid contains factors that stimulate P release and potentiate the response to hCG. The increased activity of PF associated with endometriosis and PCOS in part may have some significance in abnormal ovarian function associated with these syndromes.


Subject(s)
Ascitic Fluid/metabolism , Endometriosis/metabolism , Granulosa Cells/metabolism , Luteal Cells/metabolism , Polycystic Ovary Syndrome/metabolism , Progesterone/metabolism , Adult , Case-Control Studies , Cells, Cultured , Culture Media/chemistry , Female , Granulosa Cells/cytology , Humans , Luteal Cells/cytology , Progesterone/analysis , Radioimmunoassay
18.
Dent Mater ; 12(5): 315-8, 1996 Sep.
Article in English | MEDLINE | ID: mdl-9171000

ABSTRACT

OBJECTIVES: The aim of this investigation was to evaluate the significance of selected surface texture parameters used to describe and quantify the effect of tooth brushing with various "tooth whitening" dentifrices on a resin composite surface in vitro. METHODS: Specimens of a microfil resin composite were brushed with selected dentifrices. Surface texture profiles were acquired and analyzed both pre- and post-brushing using a contact diamond stylus. The selected parameters chosen to describe the surface texture were Ra, Rz, Rpm and the Rpm:Rz ratio. Differences between toothpastes were assessed using an ANOVA and a multiple comparisons test, the Student Newman-Keuls procedure. P and t values were calculated to determine if any of the surface roughness parameters were significantly changed by brushing. RESULTS: The results indicate that there were significant changes in the surface texture of the resin composite following tooth brushing with the selected dentifrices. For example, the use of Clinomyn significantly increased the surface roughness of the resin composite, as measured by the Rz parameter, from 2.19 +/- 1.67 microns to 10.02 +/- 2.57 microns (p < 0.05). In addition, the surface texture parameters chosen to describe the properties of the surface should reflect a knowledge of profile shape such as Rpm:Rz ratio, and care should be taken if measurements of surface texture of dental restorative materials are to be used as predictors of clinical performance. SIGNIFICANCE: All the toothpastes chosen for this investigation left a surface on the resin composite which may be prone to crack propagation during "vertical barrelling" movements generated during mastication. However, this may be more of a function of the rigidity of the restorative material rather than the surface left after tooth brushing.


Subject(s)
Composite Resins/chemistry , Dentifrices/chemistry , Analysis of Variance , Evaluation Studies as Topic , Microscopy, Electron, Scanning , Surface Properties
19.
Eur J Endocrinol ; 134(3): 379-85, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8616539

ABSTRACT

A sexual dimorphism in the pressor responsiveness to the neurohypophysial hormone vasopressin may be associated with a peripheral interaction between ovarian steroids and the neurohypophysial hormone. Indeed, the ovarian steroids may inhibit the vasopressin-dependent component of the pressor response to haemorrhage. The present study examined the recovery of the arterial blood pressure following it single large (2% v/w) haemorrhage in anaesthetized male Long Evans (LE) rats and females of the same strain during either pro-oestrous or di-oestrous phases of the reproductive cycle. In addition the same recovery process was examined in Brattleboro rats with diabetes insipidus (BDI) lacking circulating vasopressin. All BDI rats had an impaired blood pressure recovery following haemorrhage compared with male rats of the parent LE strain, and this was irrespective of sex or stage of the oestrous cycle. While the blood pressure recovery was more impaired in both groups of BDI female rats than in the males of the same strain during the first 20 min after haemorrhage (both comparisons p < 0.001; ANOVA), there was no difference between the recoveries of the female rats in pro-oestrus or di-oestrus. In contrast a significantly impaired blood pressure recovery was observed in female LE rats at pro-oestrus, when circulating ovarian steroid concentrations are raised, compared with male (p < 0.001: ANOVA) and di-oestrous (p < 0.02: ANOVA) rats of the same strain. Heart rate responses to haemorrhage showed strain differences, with LE rats having initial decreased heart rates followed by a recovery process, while the heart rate responses of BDI rats increased immediately. The novel use of the female Brattleboro rat in this study provides evidence for the existence of an important inhibitory interaction between ovarian steroids and vasopressin during the blood pressure recovery phase following haemorrhage, and indicates a possible direct influence of gonadal steroids on the recovery process.


Subject(s)
Blood Pressure , Estrus , Hemorrhage/physiopathology , Rats, Brattleboro/physiology , Animals , Diestrus , Female , Heart Rate , Hematocrit , Hemorrhage/blood , Male , Osmolar Concentration , Proestrus , Rats , Rats, Inbred Strains
20.
J Oral Rehabil ; 22(6): 421-7, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7636611

ABSTRACT

The aim of this investigation was to compare two methods of assessing the surface texture of finished dental ceramic; a laser reflectivity method (LSR) and a contact stylus tracing method. Identical ceramic blocks (Dicor MGC) were finished using a variety of techniques and devices, and the surface texture characterized by LSR and contact stylus tracing to enable comparisons to be made between the two methods. The results indicate that there is little correlation between the two measuring methods. Therefore, laser reflectivity should not be exclusively used to measure the surface texture of contoured and finished ceramic materials. The development of sophisticated surface characterization parameters suggest that the surface characteristics of dental restorations and other related surfaces should be described using more than one surface measurement parameter. Surface parameters should be chosen which can both quantify surface roughness and provide information on the shape of the surface under investigation.


Subject(s)
Dental Polishing/standards , Dental Porcelain/chemistry , Dental Polishing/methods , Image Processing, Computer-Assisted/instrumentation , Image Processing, Computer-Assisted/methods , Lasers , Regression Analysis , Reproducibility of Results , Scattering, Radiation , Signal Processing, Computer-Assisted/instrumentation , Surface Properties
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