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Biomedical subjects

S Paraskevas

Publications and source records attributed to S Paraskevas.

16 recordsLinked to original sources
PubMed2005

Optimal rinsing time for intra-oral distribution (spread) of mouthwashes.

AIM: To investigate the intra-oral spread of an erythrosine mouthwash in relation to the rinsing period. MATERIAL AND METHODS: Thirty subjects were randomly divided into two equal groups and asked to rinse with 10 ml erythrosine mouthwash for cumulative periods of 15, 30 and 60 s (Group I) and 30, 60 and 90 s (Group II). Each rinsing session was followed by new plaque measurements. After rinsing plaque was finally assessed using the erythrosine mouthwash applied by means of a cotton swab. RESULTS: In Group I there was a difference observed between the 15 s rinsing period and those of 30 and 60 s. Explorative analysis for Group I suggested that differences in both jaws and approximal sites on both vestibular and lingual surfaces appeared to have contributed to the overall difference seen between 15 and 30 s rinsing periods. Also, pre-molars and front teeth seem to have contributed to this observed difference. No differences were noted between rinsing sessions and cotton swab application for Group II or Groups I+II combined. CONCLUSIONS: Rinsing for 30 s appeared to be sufficient for all plaque-covered surfaces of the dentition to come into contact with the mouthwash.

Dental Plaque↗
PubMed2005

The effect of a dentifrice and mouth rinse combination containing amine fluoride/stannous fluoride on plaque and gingivitis: a 6-month field study.

AIM: To examine the effect of amine fluoride/stannous fluoride (AmF/SnF(2))-containing dentifrice and mouth rinse on plaque formation and gingivitis as compared with habitual oral hygiene procedures with a regular sodium fluoride (NaF) dentifrice. MATERIAL AND METHODS: In total, 22 general practices participated in this research project. The participants (N=281) were randomly assigned into two groups: the test group received an AmF/SnF(2) dentifrice-mouth rinse combination and the control group received a NaF-containing dentifrice. The patients were requested to brush twice daily for approximately 2 min. The subjects of the test group had to rinse additionally in the evening for 30 s with 10 ml of the mouth rinse. RESULTS: Both groups started with comparable scores of plaque, bleeding and staining. At 6 months, the plaque scores were 0.95 for the AmF/SnF(2) group and 0.99 for the NaF group (decrease of 16% and 10%, respectively). Bleeding scores, although significantly different from baseline, did not show differences between the two regimes. At the end of the experimental period, the overall staining was more pronounced in the AmF/SnF(2) group (41%) than the NaF group (26%). Both plaque reduction and increase in staining seemed to be correlated to the amount of mouth rinse used in the test group. CONCLUSION: In instruction-resistant patients recruited from dental practices, the combined use of AmF/SnF(2) did not decrease gingivitis at a significant level in comparison with the regular regime of two times daily brushing with an NaF-containing dentifrice. However, the above-mentioned combination resulted in greater plaque reduction than that observed with the use of the conventional dentifrice. When used according to the manufacturer's instructions, this effect on plaque scores was more pronounced.

Adult↗
PubMed2004

Effect of a combination of amine/stannous fluoride dentifrice and mouthrinse in periodontal maintenance patients.

AIM: The purpose of the present study was to evaluate the beneficial effect of using a dentifrice and mouthrinse containing amine fluoride (AmF) and stannous fluoride (SnF(2)) in a group of periodontal maintenance patients. Efficacy parameters were plaque, gingival inflammation, pocket depth and attachment loss. An additional parameter was development of stain. MATERIAL AND METHODS: In total, 80 patients who had been treated for moderate-to-severe periodontitis agreed to participate in this study. Subjects received supportive periodontal therapy at regular intervals of 3-4 months for at least a period of 1 year. The patients were randomly divided into two groups: (1). the test group used an AmF/SnF(2) dentifrice and mouthrinse and (2). the control group used a sodium fluoride (NaF)-containing dentifrice and mouthrinse. Clinical assessments were performed at baseline, 3, 6, 12, 18 and 24 months. RESULTS: The mean plaque index score after 3 months in the test group (0.24) was significantly lower than that in control group (0.34) (p<or=0.05), a difference that was maintained throughout the remainder of the study. In terms of bleeding on probing, at no point in time were significant differences between test and control group found. No significant differences were noted between the two groups, nor were there any significant changes in comparison with baseline values with respect to pocket depth and attachment level. At baseline, the mean percentage of sites with no staining was 98% for both the test and control groups. At all further assessments, the staining in both groups was elevated as compared with baseline. Smoking did not affect the outcome of the study. CONCLUSION: The combined use of an AmF/SnF(2) dentifrice and mouthrinse did not affect the parameters of inflammation (bleeding upon marginal probing and probing pocket depth), but it has shown to be more effective in terms of plaque reduction when compared with the use of an NaF dentifrice and mouthrinse in a group of periodontal patients placed under regular maintenance care.

Amines↗
PubMed2004

Amine fluoride/stannous fluoride and incidence of root caries in periodontal maintenance patients. A 2 year evaluation.

AIM: The purpose of the present study was to evaluate in a group of periodontal maintenance patients, the effect of using a dentifrice and mouthrinse containing amine fluoride (AmF) and stannous fluoride (SnF2) as compared with a dentifrice and mouthrinse both containing sodium fluoride (NaF) with regard to their root caries experience. MATERIAL: In total, 80 patients who had been treated for moderate-to-severe periodontitis agreed to participate in this study. Subjects received supportive periodontal therapy at regular intervals of 3-4 months for at least a period of 1 year. The patients were randomly divided into two groups: (1) the test group used an AmF/SnF2 dentifrice and mouthrinse and (2) the control group used an NaF-containing dentifrice and mouthrinse. Root caries was recorded at four sites per tooth at baseline and 24 months. RESULTS: An increase in number of the exposed root surfaces was noted for both groups during the experimental period (p<0.05). The mean number of active caries lesions at baseline was 2.1 and 1.8 for the test group and control group, respectively. At 24 months, the corresponding values were 1.8 for the test and 2.2 for the control group. An increase of the mean number of restored surfaces was noted for the AmF/SnF2 group (from 7.3 to 13.4) and the control group (from 7.9 to 14.7) during the course of the study. This increase was found to be statistically significant for both groups in comparison with the baseline values (p< or =0.01). No statistically significant differences were noted between groups. Further analysis of the restored surfaces revealed that the major increase in number of the restorations was associated with restorations involving three to four root surfaces in the same tooth. Molars and premolars were the teeth receiving most new restorations. CONCLUSION: The present study did not detect a difference in terms of root caries development between the two groups. Root caries development is a common finding associated with surfaces developing recession in patients once treated for periodontal problems.

Adult↗
PubMed2003

Do biliary endoprostheses decrease biliary complications after liver transplantation?

AIM: Most technical complications after orthotopic liver transplantation (OLT) are related to the biliary tree. This report reviews the role of routine intraoperative placement of stents to reduce biliary complications. METHODS: We retrospectively analyzed 396 consecutive OLTs. We reviewed rates of biliary complications after hepaticojejunostomy (HJA) as well as following choledochocholedochostomy (CCA) groups: "experimental" group (routine intraoperative biliary stenting, last 10 months), "recent" control group (nonstented, previous 10 months), "historical" control group (prior to that period of time). RESULTS: All groups were matched for donor/recipient characteristics and for graft cold/warm ischemia time. The overall prevalence of biliary complications was 30.7% after CCA versus 35% after HJA. In the experimental group 21 patients had a 4.8% biliary complication rate compared to the recent control and historical groups, where biliary complication rates were 30% and 32.6%, respectively (P <.05). CONCLUSIONS: The intraoperative use of biliary stents is feasible and appears to decrease the rate of biliary complications. These results support the need for a prospective randomized trial.

Choledochostomy↗
PubMed2003

Signals for death and differentiation: a two-step mechanism for in vitro transformation of adult islets of Langerhans to duct epithelial structures.

Phenotypic change of adult pancreatic islets has been implicated in the development of certain pancreatic cancers and in islet transplant failure. The aim of this study was to characterize intracellular events that mediate changes in adult islet phenotype. Using an in vitro islet-to-duct transformation model, canine islets were induced to undergo phenotypic transformation to duct-like epithelial structures through a two-stage process. Stage one was characterized by widespread islet cell apoptosis associated with the formation of cavitary spaces within the islets. During this stage, c-Jun N-terminal regulated kinase (JNK) and caspase-3 activities were elevated, while extracellular signal-regulated kinase (ERK) and Akt activities were decreased. The second stage of the process was characterized by an inversion in the balance in activity between these signal transduction pathways and by a concomitant decrease in apoptosis. The transformed islets were no longer immunoreactive for islet cell hormones, but expressed the duct epithelial cell marker CK-AE1/AE3. In contrast to islet cells, these duct epithelial cells were highly proliferative. To clarify the role of the identified changes in signal transduction events, we performed additional studies using pharmacological inhibitors of enzyme activity and demonstrated that inhibition of JNK and caspase-3 activity prevented cystic transformation. Our results indicate that the balance in signaling activity between ERK/Akt and JNK/caspase-3 appears to be an important regulator of islet cell death and differentiation.

Animals↗
PubMed2001

Rapid discontinuation of steroids in living donor kidney transplantation: a pilot study.

UNLABELLED: Steroids are associated with significant postoperative complications (hypertension, cosmetic changes, bone loss, hyperlipidemia, diabetes, and cataracts). Most develop early; in addition, late post-transplant steroid withdrawal in kidney transplant recipients has been associated with increased acute rejection (AR). To obviate these problems, we studied outcome of a protocol of rapid discontinuation of prednisone (RDS) (steroids stopped on POD6). Between November 1, 1999 and October 31, 2000, 51 adult living donor (LD) first transplant recipients (2 HLA-id, 28 non-id relative, 21 LURD) were immunosuppressed with thymoglobulin (1.25 mg/kg intraoperatively and then qdx4); prednisone (P) (500 mg methylprednisolone intraoperatively, 1 mg/kg x 1 day, 0.5 mg/kg x 2 days, 0.25 mg/kg x 2 days, then d/c); MMF, 1 g b.i.d.; and CSA, 4 mg/kg b.i.d. adjusted to achieve levels of 150-200 ng/mL (by HPLC). Exclusion criteria were delayed graft function or primary disease requiring P. Minimum follow-up was 5.5 months (range 5.5 to 17.5 months). Outcome was compared vs. previous cohorts of LD recipients immunosuppressed with P/AZA/CSA (n = 171) or P/MMF/CSA (n = 43) (both without antibody induction). RESULTS: For the RDS group, average CSA level (+/- S.E.) at 3 and 6 months was 190 +/- 12 and 180 +/- 9; avg. MMF dose, 1.7 +/- 0.1 g and 1.7 +/- 0.1 g. There was no significant difference in 6- and 12-month actuarial patient survival, graft survival and rejection-free graft survival between recipients on the RDS protocol vs. historical controls. For RDS recipients, actuarial 6- and 12-month rejection-free graft survival was 87%. Of the 51 RDS recipients, five (10%) have had AR (at 20 days, 1 month, 3 months, 3 months, and 3.5 months post-transplant). After treatment, all five were maintained on 5 mg P; there have been no second AR episodes. Two additional recipients were started on 5 mg P due to low white blood count (WBC) and low/no MMF. Of the 51 grafts, one has failed (death with function). Average serum Cr level (+/- S.E.) at 3 and 6 months for RDS recipients was 1.7 +/- 0.5 (NS vs. historical controls). CONCLUSION: For low-risk LD recipients, a kidney transplant with an RDS protocol does not increase risk of AR or graft loss. Future studies will need to be done to assess AR rates with an RDS protocol in cadaver transplant recipients and in recipients with delayed graft function.

Azathioprine↗
PubMed2001

Modulation of JNK and p38 stress activated protein kinases in isolated islets of Langerhans: insulin as an autocrine survival signal.

OBJECTIVE: The objective of this study was to determine the effects of islet isolation and cytokine exposure on e-JUN NH2 terminal kinase (JNK) and p38 activation and whether insulin or the p38 inhibitor PD169316 could modify the response. SUMMARY BACKGROUND DATA: Islet transplantation exposes the cells of the graft to a variety of stressful stimuli that could promote beta-cell death and lead to graft failure. METHODS: Islets from canine (n = 12) and cadaveric human (n = 6) pancreata were isolated and purified. Islets were cultured in CMRL 1066 with and without 100 ng/ml insulin. The response to cytokine stimulation with tumor necrosis factor (TNF)alpha and IL-1 beta and the p38 inhibitor PD169316 was also observed. Islet lysates were analyzed by Western blotting for total and phosphorylated JNK and p38 content. Apoptosis was assessed by TdT-mediated dUTP nick end labeling (TUNEL) assay and by a specific cell death enzyme-linked immunosorbant assay (ELISA). RESULTS: In unstimulated islets, JNK activity was highest immediately following isolation, declining over 3 days to a low baseline level. The activity of p38 was lowest immediately after isolation, increasing progressively with time. The addition of insulin resulted in a more rapid decline in JNK activity, as opposed to p38, which showed no decrease in phosphorylation in response to insulin. In the cytokine stimulation studies, IL-1 beta stimulated p38 activation in a dose dependent manner, while JNK was relatively unaffected. PD169316 (100 microg/ml) was able to inhibit p38 activation in response to the isolation procedure as well as cytokine stimulation. Apoptotic activity was highest 24 hours after isolation, and was significantly reduced when islets were maintained in insulin-supplemented medium. CONCLUSIONS: Inhibition of the stress-activated protein kinase (SAPK) pathways may be important for the maintenance of islet cell survival following islet isolation for transplantation. This study supports an autocrine role of insulin in this process.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Cell loss in isolated human islets occurs by apoptosis.

Purified islet allografts have largely failed to maintain long-term glucose homeostasis in human recipients, and the reasons for this are unclear. It is noteworthy, however, that islet isolation destroys or removes cellular and noncellular elements of the pancreas that could play an important role in supporting islet survival. The purpose of this study was to determine whether human islet isolation leads to the induction of programmed cell death. Human islets were enzymatically isolated from cadaveric donor pancreata using Liberase or Collagenase P, purified over a discontinuous BSA gradient, then cultured in RPMI 1640 at 37 degrees C in 5% CO2 for < or = 7 days. Islets were examined daily by routine histology and immunocytochemistry for islet hormones, DNA fragmentation [cell death; enzyme-linked immunosorbent assay (ELISA) and TUNEL assay] and for transglutaminase (TG) activity, two indicators of apoptosis. TG activity and DNA fragmentation increased by 1,000% and 1,890%, respectively (p < 0.05) This corresponded to the appearance of pyknotic nuclei on light microscopy, the presence of apoptotic bodies on electron microscopy, and the demonstration of TUNEL-positive cells. These were present primarily in a distribution that corresponded to the insulin-immunoreactive cells. At 5 days, 31.4 +/- 2.2% of islet cells were TUNEL positive. In summary, apoptosis of islet cells appears soon after islet isolation, and involves primarily the beta cell. This is the first report of apoptosis of islet cells after human islet isolation. The loss of beta-cell mass could be implicated in the failure of islet transplantation and merits further investigation.

Adolescent↗
PubMed1999

Activation and expression of ERK, JNK, and p38 MAP-kinases in isolated islets of Langerhans: implications for cultured islet survival.

Isolation and purification of islet cells exposes them to ischemic, osmotic and mechanical stresses. The objective of this study was to determine the roles of the MAP-kinases in islets immediately following isolation. During the first 48 h, activity of JNK1 and JNK2 declined markedly. Activity of p38 increased steadily with time in culture while extracellular signal regulated kinase (ERK) activity declined dramatically within 24 h post-isolation. High p38 activation relative to ERK activation immediately following isolation correlated with a decrease in islet survival after 36 h in culture. Absence and/or transiency of ERK signaling in conjunction with sustained activation of p38 pathway could be an important regulator of cell death in islets during and following their isolation by commonly employed procedures.

Adolescent↗
PubMed1999

Characterization of integrin expression in islets isolated from hamster, canine, porcine, and human pancreas.

The reasons for the failure of clinical islet transplantation remain obscure. Islet isolation, however, exposes the islet to variety of cellular stresses, including disruption of the cell-matrix relationship, an event associated with apoptosis. The cell-matrix relationship is characterized by an interaction between cell surface integrin receptors and matrix molecules of the surrounding basement membrane (BM). The purpose of this study was to characterize integrin expression and the distribution of the peri-insular BM in human, porcine, canine, and hamster pancreas, and after routine islet isolation. Whereas islets in the porcine pancreas do not have a demonstrable BM, islets in the human, canine, and hamster pancreas have an almost continuous BM with very little direct exocrine to endocrine cell-cell contact. After islet isolation, the BM was destroyed, only to be reestablished during the period of culture. In the pancreas of all four species, integrin alpha3 was expressed only on islet cells, and integrin alpha5 was present on islet cells as well as on acinar, centroacinar, and duct cells. Integrin alphaV was detected only in human and canine pancreas. Integrin beta1 was demonstrated only in the human pancreas. In isolated islets, integrin alpha3, alpha5, and alphaV expression decreased during the culture period and the intensity of the staining was observed to be coincident with the distribution of the BM. In summary, this is the first report of integrin expression in hamster, canine, porcine, and human islets. After islet isolation, the altered islet cell-matrix relationship is reflected both in the decrease in integrin expression and in the destruction of the peri-insular BM. These profound changes will need to be considered as the process of islet isolation for transplantation is refined. (J Histochem Cytochem 47:499-506, 1999)

Adult↗
PubMed1999

Structural and functional changes resulting from islet isolation lead to islet cell death.

BACKGROUND: Islet isolation exposes the islet to a variety of cellular stresses and disrupts the cell-matrix relationship--events known to be associated with apoptosis. The purpose of this study was to determine whether islet isolation leads invariably to islet cell death and to specify the mechanisms involved. METHODS: Canine islets were isolated using Liberase CI and purified using a centrifuge. Islets were sampled for up to 5 days in culture and analyzed by routine histology, electron microscopy, immunocytochemistry, and reticulin staining for basement membrane. Apoptosis was assessed by cell death enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated decoxyuridine triphosphate nick and labeling (TUNEL) assay. Activation of the prosurvival ERK1/2 and proapoptotic p38 and JNK were determined by immunoblotting. RESULTS: Immediately after isolation, the peri-insular basement membrane was absent, and integrin-alpha 5 expression diminished. DNA fragmentation rose from 2.5 +/- 1.8 (arbitrary units) on the day of isolation to 42.4 +/- 6.7 48 hours later (P < .05), coinciding with the appearance of pyknotic nuclei and apoptotic bodies. The apoptotic index determined by TUNEL assay increased from 5% +/- 1% on the day of isolation to 60% +/- 2% on day 5 (P < .01), and most of the affected cells were beta-cells. Finally, the p38 and JNK activity were elevated relative to ERK1/2. CONCLUSIONS: During isolation, islet cells undergo profound changes in structure and function, resulting in beta-cell apoptosis. These findings suggest that strategies directed to the manipulation of the cell-matrix relationship and the modulation of mitogen-activated protein kinase signal transduction may offer a valuable new approach to improving islet transplant outcome.

Animals↗
PubMed1996

Transdifferentiation of human islets to pancreatic ductal cells in collagen matrix culture.

Transdifferentiation is a change from one differentiated phenotype to another, involving morphological and functional phenotypic markers. Stability of the cellular phenotype is probably related to the extracellular milieu, as well as cytoplasmic and nuclear components that interact to control gene expression, and the conversion of cell phenotype is likely to be accomplished by selective enhancement of gene expression, which controls the terminal developmental commitment of cells. In this paper, we show the induction of cultured human islets cells to alter their usual phenotypic expression and attain morphological and functional characteristics of duct cells. Islets were isolated by collagenase digestion of pancreata that were removed from cadaveric organ donors. The islets were purified on a two-step density gradient of bovine serum albumin and were then placed into a three-dimensional rat-tail collagen gel matrix supplemented with NuSerum epithelial growth factor and cholera toxin. During the initial 96 h of culture, the islets underwent a cystic transformation that was associated with (1) the maintenance of immunoreactivity for neuron-specific enolase, an endocrine cell marker, but a progressive loss of insulin gene expression, (2) a loss of immunoreactivity for insulin protein, and (3) the appearance of CK-19, a marker for ductal cells. After the transformation was complete, the cells had the ultrastructural appearance of primitive duct-like cells. Cyst enlargement after the initial 96 h was associated, at least in part, with cell replication, as reflected in the 1500% increase in the incorporation of tritiated thymidine. These experiments are consistent with the transdifferentiation of an islet cell to a ductal cell. The exact mechanisms involved still need to be fully elucidated.

Autoradiography↗
PubMed1996

Alterations in pancreatic microcirculation and expression of endothelin-1 in a model of chronic pancreatitis.

Chronic pancreatitis (CP) is characterized by the presence of an inflammatory infiltrate with progressive destruction of acinar cells and fibrosis. The finding that endothelin-1 (ET-1), an endothelium-derived peptide having vasoconstrictive and mitogenic properties, reduces pancreatic blood flow (PBF) in normal rats suggested that the peptide may be associated with the reduced PBF seen in animal models of CP and with the morphological abnormalities of the disease. This study investigates changes in blood flow to the pancreas and other abdominal organs in a rat model of CP and compares ET-1 production in the pancreata of these rats and normal controls. CP was induced in male Wistar rats by the injection of oleic acid into the common bile/pancreatic duct. The radiolabeled microsphere technique was employed to measure blood flow to the pancreas, duodenum, liver, spleen, and kidneys. Immunohistochemistry was used to investigate the cellular production of ET-1. After 3 weeks, significant decreases were noted in body weight, pancreatic weight, and pancreatic DNA, amylase, and protein content in the animals with CP. PBF was reduced by 64% and duodenal blood flow by 80% relative to those in control animals. Hepatic and splenic blood flows were increased by 91 and 88%, respectively, compared to those in controls. A 50% decrease in renal blood flows were increased by 91 and 88%, respectively, compared to those in controls. A 50% decrease in renal blood flow was also seen in the experimental group after 3 weeks. Pancreata from animals with CP stained diffusely for ET-1 in the cytoplasm of vascular endothelial, acinar, and ductal cells. In the control pancreata, focal staining for ET-1 was observed only in acinar cells. This difference was significant in endothelial and ductal cells. There was weak staining of islet cells in both groups. The results suggest that elevation in local production of ET-1 may be associated with the morphological and hemodynamic changes of CP.

Animals↗