Genetic damage in human peripheral lymphocytes exposed to antimicrobial endodontic agents

Objective. Formocresol, paramonochlorophenol, or calcium hydroxide have been widely used in dental practice to eradicate bacteria and consequently to produce root canal disinfection. Taking into consideration strong evidence for a relationship between DNA damage and carcinogenesis, the purpose of the present study was to evaluate the genotoxic effects of antimicrobial endodontic compounds in human peripheral lymphocytes by single-cell gel ( comet) assay. This technique detects DNA strand breaks in individual cells.Study design. A total of 10 mu L of the tested substance solution (formocreso1, paramonochlorofeno1, and calcium hydroxide at 100-mu g/mL concentration) was added to human peripheral lymphocytes from 10 volunteers for 1 hour at 37 degrees C. The negative control group was treated with vehicle control (PBS) for 1 hour at 37 degrees C, as well. For the positive control group, lymphocytes were exposed to hydrogen peroxide at 100 mu M during 5 minutes on ice.Results. No DNA breakage was detected after a treatment of peripheral lymphocytes by formocresol, paramonochlorophenol, or calcium hydroxide at 100 mu g/mL.Conclusions. In summary, our results indicate that exposure to formocresol, paramonochlorophenol, or calcium hydroxide may not be a factor that increases the level of DNA lesions in human peripheral lymphocytes as detected by single-cell gel (comet) assay.

The frequency of 844ins68 mutation in the cystathionine beta-synthase gene is not increased in patients with venous thrombosis

Background and Objectives. A frequent mutation in the cystathionine beta-synthase (CBS) gene (844ins68, a 68-bp insertion in the coding region of exon 8) was recently discovered. In the present study we Investigated this mutation as a candidate risk factor for venous thrombosis.Design and Methods. The prevalence of the 844ins68 CBS mutation was determined in 101 patients with objectively diagnosed deep venous thrombosis and in 101 healthy controls matched for age, sex and race. PCR amplification of a DNA fragment containing exon 8 of the CBS gene was employed to determine the genotypes, Additionally, Bsrl restriction enzyme digestion of the PCR products was performed in all samples from carriers of the insertion, to test for concurrent presence of a second mutation (T833C) in the CBS gene.Results. The insertion was found in 21 out of 101 patients (20.8%; allele frequency 0.109) and in 20 out of 101 controls (19.8%; allele frequency 0.114), yielding a relative risk for venous thrombosis related to the 844ins68 CBS mutation close to 1.0. In addition, the T833C GBS mutation was detected in all alleles carrying the 844ins68 CBS insertion, confirming the co-inheritance of the two mutations.Interpretation and Conclusions. Our findings do not support the hypothesis that the 844ins68 mutation in the CBS gene is a genetic risk factor for venous thrombosis. (C)1998, Ferrata Storti Foundation.

Brain versus peripheral angiotensin II receptors in hypovolaemia: Behavioural and cardiovascular implications

1. Angiotensin (Ang)II is involved in responses to hypovolaemia, such as sodium appetite and increase in blood pressure, Target areas subserving these responses for AngII include the cardiovascular system in the periphery and the circumventricular organs in the brain.2. Conflicting data have been reported for the role of systemic versus brain AngII in the mediation of sodium appetite.3. The role for systemic AngII and systemic AngII receptors in the control of blood pressure in hypovolaemia is well established. In contrast with systemic injections, i.c.v injections of AngII non-peptide AT(1) and AT(2) receptor antagonists, such as losartan and PD123319, do not reduce arterial pressure in sodium-depleted (furosemide injection plus removal of ambient sodium for 24 h) rats. Thus, brain AngII receptors are likely not important for cardiovascular responses to hypovolaemia induced by sodium depletion.4. Intracerebroventricular injections of losartan or PD 123319 increase arterial pressure when injected at relatively high doses. This hypertensive effect is unlikely to be an agonist effect on brain AngII receptors, Increases in arterial pressure produced by i.c.v, losartan are attenuated by lesions of the tissue surrounding the anterior third ventricle (AV3V). The hypertensive effect of i.c.v, AngII is abolished by lesions of the AV3V.5. Hypertension induced by AngII receptor antagonists is consistent with hypotension induced by AngII acting in the brain, However, the full physiological significance of this hypotensive effect mediated by brain AngII receptors remains to be determined.

Identification of polymorphisms in the 5 '-untranslated region of the TAFI gene: relationship with plasma TAFI levels and risk of venous thrombosis

Background and Objectives. Thrombin activatable fibrinolysis inhibitor (TAFI) plays an important role in hemostasis, functioning as a potent fibrinolysis inhibitor. TAFI gene variations may contribute to plasma TAFI levels and thrombotic risk.Design and Methods. We sequenced a 2083-bp region of the 5 ' -regulatory region of the TAFI gene in 127 healthy subjects searching for variations, and correlated identified polymorphisms with plasma TAFI levels. TAFI polymorphisms were examined as risk factors for venous thrombosis by determining their prevalence in 388 patients with deep venous thrombosis (DVT) and in 388 controls.Results. Seven novel polymorphisms were identified: -152 A/G, -438 A/G, -530 C/T, -1053 T/C, -1102 T/G, -1690 G/A, and -1925 T/C. -152 A/G, -530 C/T and -1925 T/C were found to be in strong linkage disequilibrium, as were the -438 A/G, -1053 T/C, -1102 T/G and -1690 G/A, Plasma TAFI levels were higher in -43866/-1053CC/-1102GG/-1690AA homozygotes than In -438AG/-1053TC/-1102TG/-1690GA heterozygotes, and -438AA/-1053TT/-1102TT/-1690GG homozygotes had the lowest TAFI levels (p=0.0003). TAFI concentrations in -152AA/-530CC/-1925TT homozygotes were somewhat higher but not significantly different from levels observed for -152AG/-530CT/-1925TC heterozygotes, Taken in combination, -438AG/-1053TC/-1102TG/-1690GA and -438AA/-1053TT/-1102TT/-1690GG yielded an OR for DVT of 0.8 (95%CI: 0.6-1). in subjects aged < 35 years the OR was 0.7 (95%CI: 0.5-1.1), the OR for -152AG/-530CT/-1925TC was 1 (95%CI: 0.5-2.2) in the whole group of patients and controls, whereas in subjects aged <35 years the OR was 0.1 (95%CI: 0.02-0.9).Interpretation and Conclusions. Polymorphisms in the TAFI promoter determine plasma antigen levels and may influence the risk of venous thrombophilia. <(c)>2001, Ferrata Storti Foundation.

Metabolic acidosis in healthy mules under general anaesthesia with halothane

Objective To report the severe metabolic acidosis identified in a group of 11 healthy mules anaesthetized with halothane for castration.Study design Data generated from a prospective study.Animals Eleven mules aged 2.5-8 years, weighing 230-315 kg and 11 horses aged 1.5-3.5 years, weighing 315-480 kg.Methods Animals were anaesthetized for castration as part of an electroencephalographic study. Preanaesthetic medication was acepromazine (0.03 mg kg(-1)) administered through a preplaced jugular venous catheter. Anaesthesia was induced 30-90 minutes later with intravenous thiopental (10 mg kg(-1)). After orotracheal intubation, anaesthesia was maintained with halothane vaporised in oxygen. The animals' lungs were ventilated to maintain the end-tidal CO(2) concentration between 3.9 and 4.5 kPa (29-34 mmHg). Anaesthetic monitoring included invasive blood pressure measurement via the auricular artery (mules) and submandibular branch of the facial artery (horses). Arterial blood gas samples were drawn from these catheters at three time points during surgery and pH, PaCO(2), base excess (ecf) and HCO(3)(-) were measured. Values were compared between groups using a Mann-Whitney test. p was taken as <0.05. Results are reported as median (range).Results PaCO(2) did not differ between groups but pH was significantly lower in mules [7.178 (7.00-7.29)] compared to horses [7.367 (7.24-7.43)] (p = 0.0002). HCO(3)(-) values were significantly lower in the mules [16.6 (13.0-22.3) mM] compared to horses [23.7 (20.9-23.7) mM] (p = 0.0001), whilst base excess (ecf) was significantly more negative in the mules [-11.4 (-1.27 to -16) mM] compared to horses [-1.3 (-5.8 to +2.4) mM] (p = 0.0004).Conclusion and clinical relevance This study demonstrated severe metabolic acidosis in healthy mules, which may have prompted intervention with drug therapies in a clinical arena. It is probable that the acidosis existed prior to anaesthesia and caused by diet, but other possible causes are considered.

Effect of passive pneumoperitoneum on oesophageal pressure, cardiovascular parameters and blood gas analysis in horses

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Microscopic studies on the transition between the sigmoid sinus, the superior bulb of the jugular vein and the first portion of the internal jugular vein

The author studied the structure of the tissue components of the tunicae of the terminal segment of the sigmoid sinus, particularly at the level of the transition between the sigmoid sinus, the superior bulb of the jugular vein and the first portion of the human internal jugular vein; it was established that the transition between the sigmoid sinus and the first portion of the internal jugular vein occupies the whole extension of the superior bulb of the jugular vein up to the inferior third of the first portion of this vessel. These vascular walls exhibit a structure similar to that of the dura, i.e. the tunica adventitia is formed by fascicles of collagenic fibers which describe discontinuous spirals, more open proximal to the beginning of the first portion of the internal jugular vein. Approximately in the inferior third of the first portion of the internal jugular vein, there appear fascicles of smooth muscle fibers which are arranged similarly to those of the venous walls. The tunica intima of these vascular segments exhibits an endothelium resting on a network of elastic fibers which may play the role of an internal elastic lamina. From the bony border of the jugular foramen there originates a connective system whose fascicles of collagenic and elastic fibers incorporate to the wall of the internal jugular vein after describing a stretch in spiral around the vascular lumen.