ABSTRACT
The cytotoxic effect of iodide or thiocyanate copper(i) complexes (1-PSf, 2-PSf, 3-PSf, 4-PSf) with phosphine derived from sparfloxacin (HSf) and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) as diimine auxiliary ligands was proved in vitro on somatic (MRC-5) and neoplastic (MCF7) human cell lines. Differences in mode of action were investigated in-depth for the selected dmp and bq complexes (1-PSf, 3-PSf, respectively) by elucidation of the following: (i) the efficiency to produce reactive oxygen species (ROS) in biological systems (cyclic voltammetry); (ii) their impact on mitochondrial membrane potential; (iii) potency for the activation of caspases 3 and 9; (iv) influence on the degree of DNA degradation (comet assay). It was concluded that the apoptosis of cancer cells is directly connected to the caspase-dependent mitochondrial pathway and supported by ROS production along with irreversible DNA fragmentation. Finally, it was demonstrated that the selected copper(i) complex encapsulated inside liposomes (1-PSf-L) exhibited enhanced accumulation inside cancer cells. This resulted in its higher cytotoxicity against cancer cells with therapeutic index of ca. 60. Increased selective accumulation in active neoplasm with simultaneous enhanced bioavailability and reduced systemic toxicity of liposomal formulation of copper(i) complexes can result in the development of new copper-based therapeutics and their successful implementation in anticancer chemotherapy.
Subject(s)
Cell Death/drug effects , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Copper/chemistry , Fluoroquinolones/chemistry , Phosphines/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Caspases/metabolism , Cell Line, Tumor , Coordination Complexes/administration & dosage , Coordination Complexes/metabolism , Electrochemistry , Humans , Hydrophobic and Hydrophilic Interactions , Ligands , Liposomes , Membrane Potential, Mitochondrial/drug effectsSubject(s)
Constipation/rehabilitation , Defecation , Pelvic Floor/physiopathology , Physical Examination/methods , Physical Therapy Modalities , Adult , Biofeedback, Psychology , Chronic Disease , Constipation/physiopathology , Diet , Exercise Therapy , Female , Health Behavior , Humans , Massage , Muscle Relaxation , Quality of Life , Relaxation Therapy , Retreatment , Treatment FailureABSTRACT
In some populations, Helicobacter pylori eradication is associated with development of erosive esophagitis. The aim of this study was to evaluate the contribution of salivary bicarbonate and glycoprotein secretion to the pathogenesis of erosive esophagitis developing after H. pylori eradication. Gastroscopy and saliva collection were performed at recruitment and 12 months after completion of eradication therapy. Eighty-eight patients with duodenal ulcer were recruited to the study. Erosive esophagitis was found in 13 patients (grade A, 8 patients; grade B, 4 patients; grade C, 1 patient). Among the 74 subjects who completed the study, erosive esophagitis was detected in 21 patients (grade A, 15 patients; grade B, 6 patients); they all were successfully eradicated. Bicarbonate and glycoprotein secretion was not found to differ significantly between the subjects with and without erosive esophagitis both before and 1 year after H. pylori eradication. However, it was lower in H. pylori-infected (baseline) than in H. pylori-noninfected erosive esophagitis subjects (1 year after successful eradication) (bicarbonate 2.34 [1.29-3.40)]vs. 3.64 [2.70-4.58]micromol/min and glycoprotein 0.23 [0.15-0.31]vs. 0.35 [0.28-0.43] mg/min, P= 0.04 and P= 0.04, respectively). We conclude that changes in salivary bicarbonate and glycoprotein secretion related to H. pylori eradication do not promote the development of erosive esophagitis in duodenal ulcer patients.
Subject(s)
Duodenal Ulcer/epidemiology , Esophagitis, Peptic/epidemiology , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Helicobacter pylori/drug effects , Saliva/chemistry , Adolescent , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Anti-Ulcer Agents/therapeutic use , Bicarbonates/chemistry , Breath Tests , Cohort Studies , Comorbidity , Drug Therapy, Combination , Duodenal Ulcer/diagnosis , Duodenal Ulcer/drug therapy , Esophagitis, Peptic/diagnosis , Esophagitis, Peptic/drug therapy , Esophagoscopy/methods , Glycoproteins/metabolism , Helicobacter Infections/diagnosis , Helicobacter pylori/isolation & purification , Humans , Middle Aged , Probability , Prognosis , Saliva/metabolism , Severity of Illness Index , Statistics, Nonparametric , Treatment Outcome , Young AdultABSTRACT
PURPOSE: Since saliva protects the oesophageal and oral mucosa against hydrogen ions, the aim of the study was to establish the relationship between the secretion of gastric acid and salivary bicarbonate. MATERIAL AND METHODS: The study involved 43 Helicobacter pylori positive duodenal ulcer patients receiving: 1. omeprazole alone (O), 2. omeprazole and amoxicillin (OA) or 3. omeprazole, amoxicillin and tinidazole (OAT). In each study group the examination was performed twice, before and at the end of a two-week treatment, both under basal conditions and during a gastric secretory test with pentagastrin. Concentrations of gastric hydrogen ions and salivary bicarbonate were evaluated by the titration method. RESULTS: In all therapeutic groups analysed separately, the secretion of gastric acid as well as salivary bicarbonate decreased at the end of the treatment, however only in OA and OAT groups the differences in bicarbonate reached statistical significance. As the changes in the concentration and output of both salivary bicarbonate and gastric acid had the same direction, the three therapeutic groups (O, OA, OAT) were subjected to combined analysis. It showed that under basal conditions and during stimulation with a gastric catheter or catheter and pentagastrin, bicarbonate concentration and output were higher before than at the end of the treatment. However, no direct correlation between gastric acid secretion and salivary bicarbonate was found in groups subjected to either separate or combined analysis. CONCLUSIONS: The results of our study provide evidence for the partial involvement of hydrogen ions of gastric origin in the regulation of salivary bicarbonate secretion in duodenal ulcer patients.
Subject(s)
Amoxicillin/therapeutic use , Bicarbonates/metabolism , Duodenal Ulcer/metabolism , Gastric Acid/metabolism , Omeprazole/therapeutic use , Saliva/metabolism , Tinidazole/therapeutic use , Adult , Anti-Bacterial Agents/therapeutic use , Anti-Ulcer Agents/therapeutic use , Drug Therapy, Combination , Duodenal Ulcer/drug therapy , Female , Humans , Hydrogen-Ion Concentration/drug effects , Male , Middle Aged , Treatment OutcomeABSTRACT
BACKGROUND: Previous reports have shown that in some reflux-oesophagitis patients omeprazole therapy alters salivary secretion. The aim of the study was to examine this effect in duodenal ulcer patients. MATERIAL AND METHODS: Thirty nine Helicobacter pylori positive subjects of both sexes, predominantly men, were recruited for the study. They were taking for two weeks only omeprazole (n = 17), or omeprazole in combination with either amoxycillin or amoxycillin and tinidazole (n = 22). Salivary secretion was assessed before and at the end of the treatment, both in basal conditions and during a gastric secretory test. Gastric secretion was monitored concurrently with salivary flow rate. Additionally gastritis score and serum gastrin levels were assessed. RESULTS: Basal salivary secretions remained unchanged in patients on omeprazole monotherapy, but decreased in five of eight saliva collection periods in patients on eradication regimens. During the gastric secretory test, salivary secretions fell in both groups, but only after pentagastrin stimulation (in one collection period in patients on omeprazole, and in three collection periods in patients on eradication therapy). The observed changes in salivary secretion were inversely related to the pre-treatment gastric pH values. CONCLUSION: The influence of omeprazole and omeprazole-based eradication therapies on salivary flow rate is presumably secondary to changes in gastric pH values and is likely to be related to oesophago-salivary reflex generation.
Subject(s)
Duodenal Ulcer/drug therapy , Omeprazole/therapeutic use , Saliva/metabolism , Salivary Glands/drug effects , Adult , Aged , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/therapeutic use , Drug Therapy, Combination , Duodenal Ulcer/physiopathology , Female , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Omeprazole/administration & dosage , Omeprazole/pharmacology , Salivary Glands/metabolismABSTRACT
This article details the technique of a Cerec computer-aided designed (CAD) and computer-aided manufactured (CAM) inlay. Using a ceramic material the unit can mill an inlay from an optical "impression" that is then bonded to place using a dual-cure composite resin cement.
