Kinetic study of the plastoquinone pool availability correlated with H2O2 release in seawater and antioxidant responses in the red alga Kappaphycus alvarezii exposed to single or combined high light, chilling and chemical stresses

Under biotic/abiotic stresses, the red alga Kappaphycus alvarezii reportedly releases massive amounts of H2O2 into the surrounding seawater. As an essential redox signal, the role of chloroplast-originated H2O2 in the orchestration of overall antioxidant responses in algal species has thus been questioned. This work purported to study the kinetic decay profiles of the redox-sensitive plastoquinone pool correlated to H2O2 release in seawater, parameters of oxidative lesions and antioxidant enzyme activities in the red alga Kappaphycus alvarezii under the single or combined effects of high light, low temperature, and sub-lethal doses of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), which are inhibitors of the thylakoid electron transport system. Within 24 h, high light and chilling stresses distinctly affected the availability of the PQ pool for photosynthesis, following Gaussian and exponential kinetic profiles, respectively, whereas combined stimuli were mostly reflected in exponential decays. No significant correlation was found in a comparison of the PQ pool levels after 24 h with either catalase (CAT) or ascorbate peroxidase (APX) activities, although the H2O2 concentration in seawater (R = 0.673), total superoxide dismutase activity (R = 0.689), and particularly indexes of protein (R = 0.869) and lipid oxidation (R = 0.864), were moderately correlated. These data suggest that the release of H2O2 from plastids into seawater possibly impaired efficient and immediate responses of pivotal H2O2-scavenging activities of CAT and APX in the red alga K. alvarezii, culminating in short-term exacerbated levels of protein and lipid oxidation. These facts provided a molecular basis for the recognized limited resistance of the red alga K. alvarezii under unfavorable conditions, especially under chilling stress. © 2006 Elsevier B.V. All rights reserved.

Evaluation of the anti-inflammatory, analgesic and antipyretic activities of the natural polyphenol chlorogenic acid

Phenolic compounds are numerous and ubiquitous in the plant kingdom, being particularly present in health-promoting foods. Epidemiological evidences suggest that the consumption of polyphenol-rich foods reduces the incidence of cancer, coronary heart disease and inflammation. Chlorogenic acid (CGA) is one of the most abundant polyphenol compounds in human diet. Data obtained from in vivo and in vitro experiments show that CGA mostly presents antioxidant and anti-carcinogenic activities. However, the effects of CGA on the inflammatory reaction and on the related pain and fever processes have been explored less so far. Therefore, this study was designed to evaluate the anti-inflammatory, antinociceptive and antipyretic activities of CGA in rats. In comparison to control, CGA at doses 50 and 100 mg/kg inhibited carrageenin-induced paw edema beginning at the 2nd hour of the experimental procedure. Furthermore, at doses 50 and 100 mg/kg CGA also inhibited the number of flinches in the late phase of formalin-induced pain test. Such activities may be derived from the inhibitory action of CGA in the peripheral synthesis/release of inflammatory mediators involved in these responses. On the other hand, even at the highest tested dose (200 mg/kg), CGA did not inhibit the febrile response induced by lipopolysaccharide (LPS) in rats. Additional experiments are necessary in order to clarify the true target for the anti-inflammatory and analgesic effects of CGA. © 2006 Pharmaceutical Society of Japan.

Chloroquine inhibits Paracoccidioides brasiliensis survival within human monocytes by limiting the availability of intracellular iron

The mechanisms used by Paracoccidioides brasiliensis (Pb 18) to survive into monocytes are not clear. Cellular iron metabolism is of critical importance to the growth of several intracellular pathogens, including P. brasiliensis, whose capacity to multiply in mononuclear phagocytes is dependent on the availability of intracellular iron. Chloroquine, by virtue of its basic properties, has been shown to prevent release of iron from holotransferrin by raising endocytic and lysosomal pH, and thereby interfering with normal iron metabolism. Then, in view of this, we have studied the effects of CHLOR on P. brasiliensis multiplication in human monocytes and its effect on the murine paracoccidioidomycosis. CHLOR induced human monocytes to kill P. brasiliensis. The effect of CHLOR was reversed by FeNTA, an iron compound that is soluble at neutral to alkaline pH, but not by holotransferrin, which releases iron only in an acidic environment. CHLOR treatment of Pb 18-infected BALB/c mice significantly reduced the viable fungi recovery from lungs, during three different periods of evaluation, in a dose-dependent manner. This study demonstrates that iron is of critical importance to the survival of P. brasiliensis yeasts within human monocytes and the CHLOR treatment in vitro induces Pb 18 yeast-killing by monocytes by restricting the availability of intracellular iron. Besides, the CHLOR treatment in vivo significantly reduces the number of organisms in the lungs of Pb-infected mice protecting them from several infections. Thus, CHLOR was effective in the treatment of murine paracoccidioidomycosis, suggesting the potential use of this drug in patients' treatment.

Potential anticariogênico de soluções aciduladas com baixa concentração flúor

Objetives: The aim of this study was to verify the anticariogenic effect of acidulate solutions with low NaF concentration, using pH-cycling model and bovine enamel. Material and methods: Enamel blocks were submitted to the surface microhardness (SMH) test and randomly divided in 12 experimental and one placebo groups. The blocks were submitted to pH cycling for 7 days, with daily applications once/day of 0.05% NaF and 0.1% NaF and twice/day of 0.02% NaF solutions. Four different pH: 4.0. 5.0, 6.0 and 7.0 were used. Next, SMH test was again used to determine the surface microhardness percentage change (%SMH). Data obtained for %SMH were homogeneous and passed through variance analyses and Tukey's test (5%) as far as fluoride concentrations and pH. Resulls:The results showed that pH influenced %SMH in 0.02% NaF and 0.05% NaF solutions with pH 4.0, which had less mineral loss compared to pH 7.0 (p̃0.05). The 0.02% NaF - pH 4.0, and 0.05% NaF- pH 7.0 groups showed similar results (p>0.05). A dose-response relationship was observed among the tested solutions, with better anticariogenic effect for the 0.1% NaF solution. Conclusion: The results suggest that the addition of citric acid to acidulate mouth rinses reduce mineral loss.

Cardiovascular responses produced by central injection of hydrogen peroxide in conscious rats

Reactive oxygen species (ROS) have been shown to modulate neuronal synaptic transmission and may play a role on the autonomic control of the cardiovascular system. In this study we investigated the effects produced by hydrogen peroxide (H 2O 2) injected alone or combined with the anti-oxidant agent N-acetil-l-cysteine (NAC) or catalase into the fourth brain ventricle (4th V) on mean arterial pressure and heart rate of conscious rats. Moreover the involvement of the autonomic nervous system on the cardiovascular responses to H 2O 2 into the 4th V was also investigated. Male Holtzman rats (280-320 g) with a stainless steel cannula implanted into the 4th V and polyethylene cannulas inserted into the femoral artery and vein were used. Injections of H 2O 2 (0.5, 1.0 and 1.5 μmol/0.2 μL, n = 6) into the 4th V produced transient (for 10 min) dose-dependent pressor responses. The 1.0 and 1.5 μmol doses of H 2O 2 also produced a long lasting bradycardia (at least 24 h with the high dose of H 2O 2). Prior injection of N-acetyl-l-cysteine (250 nmol/1 μL/rat) into the 4th V blockade the pressor response and attenuated the bradycardic response to H 2O 2 (1 μmol/0.5 μL/rat, n = 7) into the 4th V. Intravenous (i.v.) atropine methyl bromide (1.0 mg/kg, n = 11) abolished the bradycardia but did not affect the pressor response to H 2O 2. Prazosin hydrochloride (1.0 mg/kg, n = 6) i.v. abolished the pressor response but did not affect the bradycardia. The increase in the catalase activity (500 UEA/1 μL/rat injected into the 4th V) also abolished both, pressor and bradycardic responses to H 2O 2. The results suggest that increased ROS availability into 4th V simultaneously activate sympathetic and parasympathetic outflow inducing pressor and bradycardic responses. © 2006 Elsevier Inc. All rights reserved.

Amphibian secretions for drug discovery studies: A search for new antiparasitic and antifungal compounds

The antiparasitic and antifungal activities of nine amphibian skin secretions were studied in different in vitro models. Seven secretions presented a considerable antiprotozoan activity and one showed promising results against Candida sp. These results can be the basis for the development of new drugs, especially for neglected parasitic diseases. © 2007 Bentham Science Publishers Ltd.

Influence of physical preconditioning on the responsiveness of rat pulmonary artery after pulmonary ischemia/reperfusion

The aim of this work was to evaluate the effect of physical preconditioning in the responsiveness of rat pulmonary rings submitted to lung ischemia/reperfusion (IR). Wistar rats were divided into three groups: Sedentary sham-operated (SD/SHAM); sedentary submitted to ischemia/reperfusion (SD/IR) and trained submitted to ischemia/reperfusion (TR/IR) animals. Exercise training consisted in sessions of 60 min/day running sessions, 5 days/week for 8 weeks. Left pulmonary IR was performed by occluding for 90 min and reperfusing for 120 min. After that, pulmonary arteries were isolated and concentration-response curves to acetylcholine (ACh), histamine (HIST), sodium nitroprusside (SNP), phenylephrine and U46619 were obtained. Neither potency (- log EC50) nor maximal responses (Emax) were modified for ACh and HIST in all groups. On the other hand, the potency for SNP was significantly increased in TR/IR group (8.23 ± 0.06) compared to SD/IR group (7.85 ± 0.04). Contractile responses mediated by a-adrenergic receptor were markedly decreased in IR groups (SD/IR: 6.75 ± 0.06 and TR/IR: 6.62 ± 0.04) compared to SD/SHAM (7.33 ± 0.05). No changes were seen for the U46619 in all groups. In conclusion, the present study shows that exercise training has no protective actions in the local blood vessel where the IR process takes place. © 2006 Elsevier Inc. All rights reserved.

Vernonia polyanthes as a new source of antiulcer drugs

Methanolic (VPME) and chloroformic (VPCL) extracts, obtained from the aerial parts of Vernonia polyanthes, were investigated for its antiulcerogenic properties. Administration of VPME (250 mg/kg) and VPCL (50 mg/kg) significantly inhibited the gastric mucosa damage (64% and 90%, respectively) caused by absolute ethanol (p.o.). Otherwise, in NSAID-induced gastric damage, their gastroprotective effects have decreased. Since the VPCL extract resulted to be more effective than the VPME we focused our efforts over VPCL action mechanism of action. © 2007 Elsevier B.V. All rights reserved.

Evaluation of micronuclei frequency in Tradescantia pallida pollen mother cells treated with ethanolic extracts isolated from Cryptocarya mandioccana, Cryptocarya moschata and Pterogyne nitens

Although herbal extracts contain several classes of compounds with pharmacological activity, they also present toxic substances with mutagenic effects. The aim of the present study was to verify the mutagenicity of Cryptocarya moschata, Cryptocarya mandioccana and Pterogyne nitens using micronucleus assay in pollen mother cells (tetrads) in Tradescantia pallida (Trad-MCN). T. pallida inflorescences were treated with different concentrations of ethanolic extracts from the selected plant species. For C. mandioccana C. moschata and P. nitens, Trad-MCN assays were carried out simultaneoulsly, followed by positive control (formaldehyde 10000 ppm), negative control (Hoagland's solution), and vehicle control (Tween 20 20% or DMSO 3%). MCN present in tetrads were quantified in 300 tetrads/inflorescence and the mean (%) and standard error (SE) were established for at least 10 inflorescences per treatment. The extracts demonstrated dose response mutagenicity (clastogenic/aneugenic effects), respectively, C. mandioccana (0.5, 1.0 and 2.0 mg/mL) and P. nitens (1.0 and 2.0 mg/mL) However, no mutagenic effect was observed to C. moschata at the concentrations evaluated in the present study. We can conclude that the C. mandioccana and P. nitens extracts demonstrated clastogenic/aneugenic effects in highest concentrations whereas C. moschata extract did not demonstrate the same effect. © 2006 Sociedade Brasileira de Toxicologia.

Cytotoxic effects of different concentrations of chlorhexidine

Purpose: To evaluate the cytotoxic effects of different concentrations of Chlorhexidine (Chx) to the odontoblast cell line MDPC-23. Methods: The odontoblast-like cells were seeded (30,000 cells/cm 2) in 60 wells of 24-well dishes and then incubated in contact with the following experimental and control solutions: Group 1: 0.0024% Chx; Group 2: 0.004% Chx; Group 3: 0.02% Chx; Group 4: Phosphate buffer saline solution (PBS, negative control); and Group 5: 0.06% H 2O 2 (positive control). Cell metabolic activity was measured by MTT assay and the cell morphology was analyzed by SEM. Results: The cytotoxic effects of Chx are dose-dependent. The reduction in the cell metabolism for Groups 1, 2, and 3 was 24.8%, 29.9% and 70.8%, respectively. No statistical difference was observed between the Groups 1 and 2 in which no significant cell morphology changes occurred. Consequently, it was concluded that 0.02% Chx solution presents high cytotoxicity to the odontoblast-like cells MDPC-23. On theother hand, 0.0024% and 0.004% Chx causes slight cytopathic effects to the cultured cells.

Methotrexate improves the health-related quality of life of children with juvenile idiopathic arthritis

Objectives: To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). Methods: Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m2/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included. Results: A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p<0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status. Conclusions: MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.

Smear layer removal and collagen fiber exposure using tetracycline hydrochloride conditioning

Aim: Smear layer removal and collagen fiber exposure may improve periodontal treatment and regeneration. This in vitro study assessed smear layer removal and collagen fiber exposure after tetracycline hydrochloride (TTC) application on root surfaces using scanning electron microscopy (SEM). Methods and Materials: Root cementum was removed with diamond burs followed by scaling and root planning. Four hundred fifty samples were divided into ten groups: a control (saline application) and nine different TTC concentrations were applied at doses of 10, 25, 50, 75, 100, 125, 150, 200, and 250 mg/ml. The TTC application was performed in all groups in three different ways (passive, brushing, and burnishing) and at three different periods of conditioning (1, 2, and 3 minutes). A previously trained, calibrated, and blind examiner evaluated photomicrographs of the samples using Sampaio's index (2005). Statistical analysis was performed using the Kruskal-Wallis' and Dunn's tests. Results: The concentrations of 50 mg/mL and 75 mg/mL applied by burnishing were the most effective in smear layer removal and collagen fiber exposure. Both the passive mode of application (p=0.0001) and 1 minute period of application (p=0.002) were the least effective. Conclusions: The concentrations of 50 mg/mL and 75 mg/mL applied by burnishing during 2 or 3 minutes were the most effective. Clinical Significance: These parameters may be applied in periodontal procedures involving TTC root conditioning to optimize results.

Anthracycline-induced cardiotoxicity

The anthracyclines constitute a group of drugs widely used for the treatment of a variety of human tumors. However, the development of irreversible cardiotoxicity has limited their use. Anthracycline-induced cardiotoxicity can persist for years with no clinical symptoms. However, its prognosis becomes poor after the development of overt heart failure, possibly even worse than ischemic or idiopathic dilated cardiomyopathies. Due to the successful action of anthracyclines as chemotherapic agents, several strategies have been tried to prevent/ attenuate their side effects. Although anthracycline-induced injury appears to be multifactorial, a common denominator among most of the proposed mechanisms is cellular damage mediated by reactive oxygen species. However, it remains controversial as to whether antioxidants can prevent such side effects given that different mechanisms may be involved in acute versus chronic toxicity. The present review applies a multisided approach to the critical evaluation of various hypotheses proposed over the last decade on the role of oxidative stress in cardiotoxicity induced by doxorubicin, the most used anthracycline agent. The clinical diagnosis and treatment is also discussed. © 2008 Bentham Science Publishers Ltd.

The possible involvement of hyperpolarizing mechanisms in histamine-induced relaxation of the rat portal vein

The present study evaluated the effects of histamine 10 -2 M on longitudinal preparations of rat portal vein. It was observed that histamine 10 -2 M induced relaxation of rat portal vein preparations pre-contracted with phenylephrine 10 -4 M. On the other hand, no pharmacological effects were observed in preparations not pre-contracted. The observed histamine-induced relaxing effect was absent in preparations pre-contracted with KCl (120 mM) or in the presence of depolarizing nutritive solution. However, the histamine-induced relaxation was still present in the endothelium-removed preparations. The histamine-induced relaxation also was not prevented by astemizole (10 -6 M, 10 -5 M and 10 -4 M), cimetidine (10 -5 M, 10 -4 M and 10 -3 M) or thioperamide (10 -6 M, 10 -5 M and 10 -4 M), selective antagonists H 1, H 2 and H 3, respectively. The presence of L-NAME 10 -4 M or L-NAME 10 -4 M plus indomethacin 10 -5 M also did not prevent the histamine-induced relaxation observed in rat portal vein. Thus, the histamine-induced relaxation observed in rat portal vein appears to involve a non-endothelial hyperpolarizing mechanism independent of H 1, H 2 and H 3 receptors.

Interação entre grau de perda auditiva e o incômodo com zumbidos em trabalhadores com história de exposição ao ruído

Hearing loss and tinnitus impact the lives of workers in every instance of their lives. Aim: this paper aims to investigate the existence of a dose-response relationship between hearing loss and tinnitus by determining whether higher levels of hearing loss can be associated with increased tinnitus-related discomfort. Materials and method: this cross-sectional case study assessed 284 workers exposed to occupational noise through pure tone audiometry. Test results were categorized as defined by Merluzzi. Individuals complaining of tinnitus answered the adapted and validated Brazilian Portuguese version of the Tinnitus Handicap Inventory. A generalized linear model was adjusted for binomial data to test the interaction between these factors. Results: over 60% of the ears analyzed had hearing loss, while more than 46% of them had tinnitus. Tinnitus prevalence and risk rates increased as pure tone audiometry results got worse. The association between both, considering all hearing loss degrees, was statistically significant. Conclusion: the results point to a statistical association between hearing loss and tinnitus; the greater the hearing loss, the greater the discomfort introduced by tinnitus. 2009 © Revista Brasileira de Otorrinolaringologia.