Levels of oxidative stress biomarkers and bone resorption regulators in apical periodontitis lesions infected by Epstein-Barr virus.

AIM: To investigate whether apical periodontitis lesions infected by Epstein-Barr virus (EBV) exhibit higher levels of oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and oxidized glutathione (GSSG)] and bone resorption regulators [receptor activator of nuclear factor (NF-κB) ligand (RANKL) and osteoprotegerin (OPG)] compared to EBV-negative periapical lesions and healthy pulp tissues. METHODOLOGY: The experimental group consisted of 30 EBV-positive and 30 EBV-negative periapical lesions collected in conjunction with apicoectomy. The pulp tissues of 20 impacted third molars were used as healthy controls. The qualitative and quantitative analysis of EBV was performed by nested and real-time polymerase chain reaction (PCR), respectively. The levels of RANKL and OPG were analysed by reverse transcriptase real-time PCR. The levels of 8-OHdG and GSSG were determined by enzyme-linked immunosorbent assay (ELISA). Mann-Whitney U-test and Spearman's correlation were used for statistical analysis. RESULTS: The levels of RANKL, OPG, 8-OHdG and GSSG were significantly higher in apical periodontitis lesions compared to healthy pulp controls (P = 0.001, P < 0.001, P < 0.001 and P < 0.05, respectively). RANKL and OPG mRNA expression was significantly higher in EBV-positive compared to EBV-negative periapical lesions (P < 0.05). There was no significant correlation between EBV copy numbers and levels of RANKL, OPG, 8OH-dG and GSSG in apical periodontitis. CONCLUSION: Levels of bone resorption regulators and oxidative stress biomarkers were increased in apical periodontitis compared to healthy pulp tissues. EBV-positive periapical lesions exhibited higher levels of RANKL and OPG compared to EBV-negative periapical lesions. EBV may contribute to progression of apical periodontitis via enhanced production of bone resorption regulators.

A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder.

As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.

A paradigm to investigate the regulation of cocaine self-administration in human cocaine users: a randomized trial.

RATIONALE: We recently conducted a pilot study supporting the feasibility, safety, and validity of a human laboratory model of ad libitum cocaine administration in which subjects self-selected the timing of infusions. The current study extends this work to include a randomized design with a test-retest component in a larger sample. OBJECTIVES: To investigate the regulation of cocaine intake by humans and its effects on subjective and cardiovascular responses. MATERIALS AND METHODS: Subjects were 14 non-treatment seeking volunteers (10 M, 4 F) with cocaine abuse/dependence. Subjects self-administered cocaine infusions (0, 8, 16, and 32 mg/70 kg) over a 2-h period under a fixed ratio 1, 5-min time-out schedule on 4 consecutive days. A fifth session was conducted at 16-mg dose to assess the paradigm's test-retest reliability. RESULTS: Subjects regulated their cocaine intake in a dose-dependent fashion. Self-reports of cocaine-related subjective effects (e.g., "high" and "stimulated") also varied in a dose-dependent way. Test-retest data and the randomized design support the conclusion that such effects are not due to tolerance or other experimental artifacts. CONCLUSION: The current study replicates prior work demonstrating the feasibility, safety, and validity of our human laboratory paradigm of cocaine administration in a larger sample using a randomized design. The current study also shows the test-retest reliability of these methods, establishing its utility for comparisons of experimental interventions (e.g., pharmacological treatments). Finally, the current study suggests that factors other than drug-induced euphoria (i.e., "high") contribute to the regulation of cocaine-taking behaviors in humans.

Surgical treatment of a postpartal spontaneous left main coronary artery dissection.

We report on a 34-year-old woman who presented with acute anterolateral myocardial infarction 12 weeks postpartum. Cardiac catheterization documented a left main coronary artery dissection with complete occlusion of the left anterior descending artery. The surgical treatment and the complicated postoperative course are discussed here.

Pentadecapeptide BPC 157 attenuates gastric lesions induced by alloxan in rats and mice.

A diabetogenic alloxan regimen produced lesions in all stomachs of treated animals, either rats (200 mg x kg(-1) s.c.) or mice (400 mg x kg(-1) i.p.). In control animals, the lesions, when developed (i.e. 24 h following application), appear to be quite sustained, and consistently present also after 1 or 2 weeks. The application of the pentadecapeptide BPC 157 (10 microg or 10 ng x kg(-1) i.p. coadministered together with alloxan) would significantly attenuate these lesions' appearance. This beneficial effect seems to be present in either rats or mice and in either of the tested intervals. Importantly, the beneficial effect seems to be shared by both microgram and nanogram regimens.

Carbon monoxide poisoning and treatment with hyperbaric oxygen in the subacute phase.

The use of normobaric versus hyperbaric (>2 atm) oxygen in the treatment of carbon monoxide intoxication continues to be a matter of debate despite reports of increased efficacy with hyperbaric oxygen. When hyperbaric oxygen is used, immediate treatment is preferred for best results. The therapeutic window of time, however, is unknown. A patient presented with acute confusion and partial retrograde and total anterograde memory loss due to carbon monoxide poisoning. He was initially treated with normobaric oxygen and failed to show appreciable improvement. One month after carbon monoxide exposure the patient underwent treatment with hyperbaric oxygen and showed appreciable symptom relief confirmed by clinical findings and neuropsychological testing. This case shows that hyperbaric oxygen may be efficacious in the recovery of neuropsychiatric function up to 1 month after carbon monoxide induced brain injury.

BPC 157's effect on healing.

The 15 amino acid agent BPC 157, showing a wide range of organoprotective action in different experimental models, was used in our experiments in order to establish its influence on different elements connected with the healing process. Elements thought to be of greatest importance in the process of healing are formation of granulation tissue, angiogenesis and production of collagen. In our work we tested the influence of BPC 157 on: granulation tissue and collagen formation, on angiogenesis as well as on tensile strength development, using three experimental rat models: 1) skin incisional wounds; 2) colon-colon anastomoses; and 3) angiogenesis model with synthetic sponge implantation. The specimens were histologically assessed for collagen, reticulin and blood vessels using scoring and morphometry. In all experiments significant differences between BPC 157-treated animals and controls were found, showing a strong, promoting involvement of BPC in the healing process. It is worth noting that these effects were achieved by different routes of application, including intragastric and local, making BPC 157 a potentially useful therapeutic agent.

Cardiac myxoma: diagnostic approach, surgical treatment and follow-up. A twenty years experience.

At the University Department of Cardiovascular Surgery in Zagreb, Croatia, we treated 81 patients with primary intracardiac myxoma, in a period from January 1975 to December 1994. There were 55 female and 26 male pts, in age from 1 month to 80 years, mean 46+/-15 years. Clinical manifestations varied from no symptoms and very poor or no clinical signs to various manifestations of chronic or acute congestive heart failure, syncope and arrhythmias with or without systemic findings such as high erythrocyte sedimentation rate, anaemia, leucocytosis, elevated gamma globulin, thrombocytopenia or low grade fever, as well as cerebrovascular accidents due to tumour embolization. Cardiac symptoms were predominant in 54 pts (66.6%) and cerebrovascular in 20 pts (24.7%). Seven pts (8.6%) were symptomless and discovered accidentally, mostly regarding on an unexplained heart murmur. In almost all the patients preoperative diagnosis of intracardiac myxoma was sufficiently established by echocardiography. The tumour was located in the left atrium in 62 pts (76.5%) and in the right atrium in 19 pts (23.5%). Delay from the onset of symptoms to the diagnosis was 6 months in average (range 10 days to 25 months). The average waiting for the operation was 9 days (range from 1 to 60 days). The echocardiographic diagnosis was confirmed during intraoperative examination followed by histological analysis. All pts underwent excision of myxoma using cardiopulmonary bypass with core and topical hypothermia and cold crystaloid cardioplegia. According to the additional preoperative and intraoperative findings, in 6 pts sinchronous mitral valve reconstruction, in 3 pts artificial mitral valve implantation and in 2 pts atrial wall reconstruction was performed. There was no perioperative mortality. After the operation, we could not evaluate all the patients long enough, mostly because of some paramedical circumstancies, such as war, migrations, etc. Twenty two pts undevent evaluation for at least 5 years after the operation. Among them there was no evidence of the tumour recurrence, 15 pts were asymptomatic and 7 had NYHA II class symptoms. For 17 pts with a left atrial myxoma preoperative and postoperative echocardiographic data were available for comparison, showing a significant reduction of the left atrial diameter (p<0.001) during the postoperative follow-up. Our data, presenting one of the biggest reports concerning cardiac myxomas, showed a broad spectrum of their clinical presentation, importance of echocardiography in diagnosing and postoperative follow-up and efficacy of a proper surgical intervention as a definite, curative therapy since there were no deaths and no significant cardiac dysfunction neither tumour reccurrence as well.

Wound infection after median sternotomy during the war in Croatia.

From 1990 to 1994 at Clinical Hospital Center, Zagreb, 1904 median sternotomies were performed for cardiac operations. Patients shared the same intensive care unit (ICU) with the wounded persons, admitted to the hospital from battlefield. Infection developed in 124 patients, an incidence of 6.51%. Methicillin resistant Staphylococcus aureus (MRSA) was isolated from 90, methicillin resistant Staphylococcus epidermidis (MRSE) from 19, and gram negative bacilli (GNB) from 56 patients, Pseudomonas aeruginosa in 2, and Clostridium pneumoniae in 1 case. Ninety-six patients (5.04%) developed superficial localized infection of subcutaneous tissues and they were treated with frequent dressing changes with antibiotic-soaked gauze in combination with systemic antibiotics. Twenty-eight patients (1.47%) developed mediastinitis and sternal dehiscence. They were treated by operative debridement followed by reclosure of the sternum with continuous antibiotic irrigation. We obtained satisfactory results with our method of closure of sternum which is a modification of Robicsek's technique. Nine of them required further operation. In seven cases we performed muscle flaps and in two omentoplasty. One hundred and twenty patients were discharged in satisfactory condition. The uncontrolled mediastinal sepsis caused death in 4 patients. Higher infection rate after median sternotomy during 1991 and 1992 could be possibly explained with the war circumstances in Croatia, and especially with MRSA strain becoming endemic in surgical ICU.

PTH-sensitive K(+)- and voltage-dependent Pi transport by chick renal brush-border membranes.

Brush-border membrane vesicles (BBMV) from chick (Gallus gallus) kidneys were used to examine possible pathways of Pi transport associated with Pi secretion. Preloading with 6 mM Pi trans-stimulated 32Pi uptake in the absence of Na+, indicating facilitation. Inside-positive voltage (100 mM K+, out > in, +valinomycin) increased Pi uptake from 161 +/- 4.4 to 241 +/- 16.1 pmol.mg protein-1.5s-1 at pH 7.5 (in = out). Gradients characterized by extravesicular pH (pHo) of 5.5 vs. intravesicular pH (pHi) of 7.5, 100 mM K+ (out > in), without and with valinomycin, further increased uptake to 664 +/- 148.5 and 946 +/- 90.8 pmol.mg protein-1.5s-1, respectively. Carbonyl cyanide m-chlorophenylhydrazone (CCCP) had no effect on the latter response, but with 100 mM K+ (in = out), valinomycin decreased the response more than one-half, implicating a H+ diffusion potential. Generation of this potential with pHo 5.5 vs. pHi 7.5 and CCCP did not drive concentrative Pi uptake in absence of K+. Parathyroid hormone (PTH) treatment significantly increased this BBMV K(+)- and voltage-dependent Pi up-take compared with the parathyroidectomized (PTX) condition. The values of maximal uptake rate (Vmax) in PTH vs. PTX BBMV were 5,330 and 1,976 pmol.mg protein-1.5s-1, respectively. K(+)-dependent transport was inhibited by arsenate, phosphonoacetic acid, and vanadate. Together, the data indicate that this PTH-sensitive, voltage- and K(+)-dependent monovalent Pi transporter could be the mechanism by which Pi exits, cell-to-lumen, during renal tubular Pi secretion.

Gastric lesion development in normal and pylorus ligated rats after cervical vagotomy.

The main purpose of this study was to further investigate the effects of vagotomy on gastric lesion development. In contrast to the usual subdiaphragmal vagotomy, a different vagotomy at the level of the trigonum caroticum was used both alone and in combination with pylorus ligation (done immediately after vagal transection). The animals were killed 15 min, 30 min, 1 h and 6 h following vagotomy. No damaging effects of sham-vagotomy, or obvious negative effects of cervical vagotomy were noted. Prominent lesions appeared after 1 h in rats subjected to cervical vagotomy and significantly increased lesions in the early period of pylorus ligation were noted. No further aggravation in pylorus ligated rats (even an apparent amelioration at 1-h interval) and no lesions in rats with cervical vagotomy in the latter period could be explained in terms of a lack of reactivity due to exhaustion preceding fatal outcome. Consistent with this, the rats subjected to cervical vagotomy died shortly after the 6-h period.