Comparison of in vitro proliferative capacity of human periodontal ligament cells in juvenile and aged donors

OBJECTIVE: The aim of this study is to compare the in vitro proliferative capacity of periodontal ligament (PDL) cells from aged and juvenile donors.
MATERIALS AND METHODS: Flow-cytometric analysis of the cell cycle was used to compare the length of each cell cycle, and the ratio of the cells progressing through the cycles between four PDL cells from juvenile donors and four cells from aged donors. Then, replicative capacity of the PDL cells from three juvenile and three aged donors was compared by serial cultureS. Finally, expression of c-fos was compared between cells proliferating and cells which had reached senescent.
RESULTS: Flow-cytometric analysis of the cell cycle had revealed that although there were no differences in the length of each phase of the cell cycle, significant differences were found in the ratio of the cells entering from Gap 1 to DNA synthesis phase of the cell cycle ( P < 0.025).Replicative capacity was much longer in two cells from juvenile donors (about 20 population doublings), while all cells from aged donors showed short dividing abilities (less than eight population doublings), hence entered senescent phases shortly. Additionally, no c-fos was detected in cells which had reached senescence upon stimulation with serum.
CONCLUSIONS: It is generally believed that aged humans have an impaired wound healing ability. We believe that more fibrotic PDL tissues seen in aged humans might be the reason for this, and suggest that this phenomena might be due to the progressive accumulation of senescent cell populations.     

DENTAL CARIES AND PERIODONTAL DISORDERS IN CHRONIC LIVER DISEASE

Bacterial infections are frequent complications in patients with chronic liver disease (CLD). A potential source of infection may be dental foci. This study was carried out to assess the association of CLD with dental caries and periodontal disease. Dental caries and periodontal examinations were performed prospectively in patients with CLD (group A) and controls without any liver disease (group B). Similar examination was also carried out in alcoholics without liver disease (group C) as well as in cases with portal hypertension but no liver disease (group D) i.e. patients with Non Cirrhotic Portal Fibrosis and Extrahepatic portal obstruction. A total of 231 subjects (Group A:83, group B: 75, group C:46 and group D:27) were studied. Group A included 32 cases with chronic hepatitis B&C, 26 with alcoholic cirrhosis, 14 with postnecrotic cirrhosis, and 11 with cryptogenic cirrhosis. Measures of oral hygiene (p < 0.01), dental care (p < 0.001), and periodontal parameters were worse and the number of teeth requiring treatment (p < 0.05) was higher in alcoholics with or without cirrhosis than in healthy subjects and nonalcoholic patients with cirrhosis. Alcoholics had a lower, total number of teeth than patients without alcohol abuse and healthy controls (p < 0.01). The dental caries and periodontal status of patients with nonalcoholic cirrhosis did not differ significantly from group B. The severity and duration of liver disease had no influence on dental caries and periodontal disease. The presence of chronic alcohol abuse rather than cirrhosis or portal hypertension is a major predisposing factor for dental caries and periodontal diseases. In alcoholics, these diseases appear to be caused primarily by bad oral hygiene and poor dental care.KEY WORDS: Alcohol abuse, Chronic liver disease, Dental caries, Periodontal disease     

Randomised clinical trial: the efficacy and safety of propionyl-L-carnitine therapy in patients with ulcerative colitis receiving stable oral treatment

Aliment Pharmacol Ther 2011; 34: 1088–1097

Summary

Background Ulcerative colitis (UC) is characterised by impaired fatty‐acid oxidation; l ‐carnitine has a key role in fatty‐acid metabolism and short‐chain fatty acids such as butyrate and propionate are important energy source for intestinal epithelial cells. Aim To evaluate efficacy and safety of colon‐release propionyl‐l ‐carnitine (PLC) in patients with mild‐to‐moderate UC receiving stable oral aminosalicylate or thiopurine therapy. Methods In a multicentre, phase II, double‐blind, parallel‐group trial, patients were randomised to receive PLC 1 g/day, PLC 2 g/day or placebo. Main inclusion criteria were as follows: age 18–75; disease activity index (DAI) score 3–10 inclusive, be under oral stable treatment with aminosalicylate or thiopurine. The primary endpoint was clinical/endoscopic response, defined as a decrease in DAI score ≥ 3 points or remission, defined as a DAI score ≤ 2 with no individual sub‐score > 1. Results Of 121 patients who were randomised, 57 of 79 (72%) patients receiving PLC (combined 1 g and 2 g cohort) had a clinical/endoscopic response vs. 20 of 40 (50%) receiving placebo (P = 0.02). Specifically, in PLC 1 g/day group, 30 of 40 (75%) patients had clinical/endoscopic response (P = 0.02 vs. placebo) and 27 of 39 (69%) in the PLC 2 g/day group (P = 0.08 vs. placebo). Rates of remission were 22/40 (55%), 19/39 (49%), 14/40 (35%) in the PLC 1 g, PLC 2 g, and placebo groups, respectively. PLC had a similar safety profile to placebo; the most common adverse events were gastrointestinal. Conclusion Propionyl‐l ‐carnitine 1 g/day should be investigated further as a co‐treatment for mild‐to‐moderate ulcerative colitis (NCT‐01026857).     

Cytokines and cholinergic signals co-modulate surgical stress-induced changes in mood and memory

Inflammatory cytokines and the cholinergic system have been implicated in the effects of stressors on mood and memory; however, the underlying mechanisms involved and the potential interrelationships between these pathways remain unclear. To address these questions, we administered neuropsychological tests to 33 generally healthy surgery patients who donated blood samples several days prior to undergoing moderate surgery (baseline), on the morning of the surgery (i.e., a psychological stressor), and one day after surgery. Eighteen control subjects were similarly tested. Serum levels of inflammatory cytokines, acetylcholinesterase (AChE) activity, and the stressor-inducible AChE-R variant were measured. An elevation in anxiety levels, an increase in depressed mood, and a decline in declarative memory were observed on the morning of the surgery, prior to any medical intervention, and were exacerbated one day after surgery. The surgical stressor-induced elevated IL-1 beta levels, which contributed to the increased depressed mood and to the post-surgery increase in AChE-R expression. The latter increase, which was also predicted by pre-surgery AChE-R and post-surgery mood disturbances, was associated with exacerbated memory impairments induced by surgery. In addition, elevated levels of AChE-R on the morning of the surgery predicted the post-surgery elevation in IL-6 levels, which was associated with amelioration of the memory impairments induced by surgery. Taken together, these findings suggest that exposure to a surgical stressor induces a reciprocal up-regulation of AChE-R and pro-inflammatory cytokines, which are involved in regulating the surgery-induced mood and memory disturbances.     

Comparison of postoperative pain management techniques on endocrine response to surgery: a randomised controlled trial

The present study compared three postoperative pain management techniques in patients undergoing lower abdominal surgery: intermittent opiate regimen (IOR), patient-controlled analgesia (PCA), and patient-controlled epidural analgesia (PCEA), on cortisol and prolactin levels during the first 48 h postoperatively. Ninety-two patients scheduled for a lower abdominal surgery, were randomly assigned to one of three study groups: IOR (N=31), PCA (N=31), and PCEA (N=30). Patients of the IOR group received postoperatively 50-75 mg of pethidine IM on demand. Patients of the PCA group received a loading dose of morphine (3-4 mg), followed by 1mg bolus of morphine IV per demand. Patients of the PCEA group received 3 ml of 0.1% bupivacaine plus 2 microg/ml of fentanyl per demand, with continuous background infusion of 6ml/h. Venous blood samples were collected preoperatively, and 24 and 48 h after surgery, and were later assayed for serum cortisol and prolactin levels. Patients of the PCEA group exhibited diminished postoperative elevation of serum cortisol levels at 24 and 48 h (24.4, 18.6 microg/dl, respectively) compared with both IOR (31.9, 21.9) and PCA (28.5, 22.3) groups. Similarly, patients of the PCEA group exhibited diminished postoperative elevation of serum prolactin level (20.7, 15.7 ng/mL) compared with PCA (24.9, 17.1) group. The present results indicate that the PCEA technique offers an advantageous treatment associated with reduced postoperative pain, and attenuated neuroendocrine response.     

Knockdown of endoplasmic reticulum chaperone BiP leads to the death of parvocellular AVP/CRH neurons in mice

Arginine vasopressin (AVP) is expressed in both magnocellular (magnAVP) and parvocellular AVP (parvAVP) neurons of the paraventricular nucleus, and AVP colocalizes with corticotropin-releasing hormone (CRH) only in the parvocellular neurons. The immunoglobulin heavy chain binding protein (BiP) is a major endoplasmic reticulum (ER) chaperone which regulates the unfolded protein response under ER stress. We previously demonstrated that knockdown of BiP in magnAVP neurons exacerbated ER stress, which resulted in the autophagy-associated cell death of magnAVP neurons. Using the same approach, in the present study we examined the role of BiP in mouse parvAVP/CRH neurons. Our data demonstrate that BiP is expressed in mouse parvAVP/CRH neurons under nonstress conditions and is upregulated in proportion to the increase in CRH expression after adrenalectomy. For BiP knockdown in parvAVP/CRH neurons, we utilized a viral approach in combination with shRNA interference. Knockdown of BiP expression induced ER stress in parvAVP/CRH neurons, as reflected by the expression of C/EBP homologous protein. Furthermore, BiP knockdown led to the loss of parvAVP/CRH neurons after 4 weeks. In summary, our results demonstrate that BiP plays a pivotal role in parvAVP/CRH neurons, which function as neuroendocrine cells producing a large number of secretory proteins.