Anti-Trypanosoma cruzi Properties of Sesquiterpene Lactones Isolated from Stevia spp.: In Vitro and In Silico Studies.

Stevia species (Asteraceae) have been a rich source of terpenoid compounds, mainly sesquiterpene lactones, several of which show antiprotozoal activity. In the search for new trypanocidal compounds, S. satureiifolia var. satureiifolia and S. alpina were studied. Two sesquiterpene lactones, santhemoidin C and 2-oxo-8-deoxyligustrin, respectively, were isolated. These compounds were assessed in vitro against Trypanosoma cruzi stages, showing IC50 values of 11.80 and 4.98 on epimastigotes, 56.08 and 26.19 on trypomastigotes and 4.88 and 20.20 µM on amastigotes, respectively. Cytotoxicity was evaluated on Vero cells by the MTT assay. The effect of the compounds on trypanothyone reductase (TcTR), Trans-sialidase (TcTS) and the prolyl oligopeptidase of 80 kDa (Tc80) as potential molecular targets of T. cruzi was investigated. Santhemoidin C inhibited oligopeptidase activity when tested against recombinant Tc80 using a fluorometric assay, reaching an IC50 of 34.9 µM. Molecular docking was performed to study the interaction between santhemoidin C and the Tc80 protein, reaching high docking energy levels. Plasma membrane shedding and cytoplasmic vacuoles, resembling autophagosomes, were detected by transmission microscopy in parasites treated with santhemoidin C. Based on these results, santhemoidin C represents a promising candidate for further studies in the search for new molecules for the development of trypanocidal drugs.

Novel tick glutathione transferase inhibitors as promising acaricidal compounds.

Ticks are important ectoparasites with a worldwide distribution. The most commonly used method for tick control involves the use of acaricides. The main problem is that its indiscriminate use has led to the selection of resistant tick populations. Glutathione transferases (GSTs) are enzymes that play an important role in the detoxification of several types of compounds used in commercial tick control products. This work aims to find new bioactive molecules through in vitro assays with a panel of 160 molecules with putative inhibitory activity on the Rhipicephalus microplus GST enzyme (RmGST). Also, selected molecules were tested against GSTs from other tick species; Rhipicephalus decoloratus, Amblyomma variegatum, Rhipicephalus appendiculatus, and Haemaphysalis longicornis. The first screening on RmGST identified 30 compounds with the ability to modify the enzymatic activity of this enzyme. These compounds included different chemical families, like chalcones, diarylideneketones, flavone, thiazoles, thiourea, steroids, thiadiazines, indazoles, and hydrazine. The most potent compounds against RmGST belong to the diarylideneketones family with an inhibition concentration of 50% of activity (IC50) between 7-50 µM. Interestingly, one of the most potent compounds was also an inhibitor of the GST from other tick species. Experiments with R. microplus adults and larvae showed toxicity at 150 µM, suggesting a potential acaricidal effect of these molecules.

Clinical Features of de novo Pure 16q21q24.1 Chromosome Duplication.

Pure partial duplications of the long arm of chromosome 16 are rare and few cases are described with delineation by chromosomal microarray. Data about clinical abnormalities of pure partial 16q duplications are incomplete because many individuals die during the perinatal period. We describe the clinical features of a 47-month-old Brazilian girl with 16q21q24.1 duplication. To the best of our knowledge, she is the first person with this specific chromosome segment duplication, and we compare her phenotype with the only reported individual alive with intermediate-distal pure 16q duplication.

Oxidative Modification of Proteins: From Damage to Catalysis, Signaling, and Beyond.

Significance: The systematic investigation of oxidative modification of proteins by reactive oxygen species started in 1980. Later, it was shown that reactive nitrogen species could also modify proteins. Some protein oxidative modifications promote loss of protein function, cleavage or aggregation, and some result in proteo-toxicity and cellular homeostasis disruption. Recent Advances: Previously, protein oxidation was associated exclusively to damage. However, not all oxidative modifications are necessarily associated with damage, as with Met and Cys protein residue oxidation. In these cases, redox state changes can alter protein structure, catalytic function, and signaling processes in response to metabolic and/or environmental alterations. This review aims to integrate the present knowledge on redox modifications of proteins with their fate and role in redox signaling and human pathological conditions. Critical Issues: It is hypothesized that protein oxidation participates in the development and progression of many pathological conditions. However, no quantitative data have been correlated with specific oxidized proteins or the progression or severity of pathological conditions. Hence, the comprehension of the mechanisms underlying these modifications, their importance in human pathologies, and the fate of the modified proteins is of clinical relevance. Future Directions: We discuss new tools to cope with protein oxidation and suggest new approaches for integrating knowledge about protein oxidation and redox processes with human pathophysiological conditions. Antioxid. Redox Signal. 35, 1016-1080.

Oxidative modification of proteins: from damage to catalysis, signaling and beyond

Significance: The systematic investigation of oxidative modification of proteins by reactive oxygen species started in 1980. Later, it was shown that reactive nitrogen species could also modify proteins. Some protein oxidative modifications promote loss of protein function, cleavage or aggregation, and some result in proteotoxicity and cellular homeostasis disruption. However, not all oxidative modifications are necessarily associated with damage, as with Met and Cys protein residue oxidation. In these cases, redox state changes can alter protein structure, catalytic function, signaling processes in response to metabolic and/or environmental alterations. This review aims to integrate the present knowledge on redox modifications of proteins with their fate and role in redox signaling and human pathological conditions. Critical issues: It is hypothesized that protein oxidation participates in the development and progression of many pathological conditions. However, no quantitative data has been correlated with specific oxidized proteins or the progression or severity of pathological conditions. Hence, the comprehension of the mechanisms underlying these modifications, their importance in human pathologies and, the fate of the modified proteins is of clinical relevance. Future directions: We discuss new tools to cope with protein oxidation and suggest new approaches for integrating knowledge about protein oxidation and redox processes with human pathophysiological conditions.

White Rice Intake and Incident Diabetes: A Study of 132,373 Participants in 21 Countries.

OBJECTIVE: Previous prospective studies on the association of white rice intake with incident diabetes have shown contradictory results but were conducted in single countries and predominantly in Asia. We report on the association of white rice with risk of diabetes in the multinational Prospective Urban Rural Epidemiology (PURE) study. RESEARCH DESIGN AND METHODS: Data on 132,373 individuals aged 35-70 years from 21 countries were analyzed. White rice consumption (cooked) was categorized as <150, ≥150 to <300, ≥300 to <450, and ≥450 g/day, based on one cup of cooked rice = 150 g. The primary outcome was incident diabetes. Hazard ratios (HRs) were calculated using a multivariable Cox frailty model. RESULTS: During a mean follow-up period of 9.5 years, 6,129 individuals without baseline diabetes developed incident diabetes. In the overall cohort, higher intake of white rice (≥450 g/day compared with <150 g/day) was associated with increased risk of diabetes (HR 1.20; 95% CI 1.02-1.40; P for trend = 0.003). However, the highest risk was seen in South Asia (HR 1.61; 95% CI 1.13-2.30; P for trend = 0.02), followed by other regions of the world (which included South East Asia, Middle East, South America, North America, Europe, and Africa) (HR 1.41; 95% CI 1.08-1.86; P for trend = 0.01), while in China there was no significant association (HR 1.04; 95% CI 0.77-1.40; P for trend = 0.38). CONCLUSIONS: Higher consumption of white rice is associated with an increased risk of incident diabetes with the strongest association being observed in South Asia, while in other regions, a modest, nonsignificant association was seen.

Unraveling the effects of peroxiredoxin 2 nitration; role of C-terminal tyrosine 193.

Peroxiredoxins (Prx) are enzymes that efficiently reduce hydroperoxides through active participation of cysteine residues (CP, CR). The first step in catalysis, the reduction of peroxide substrate, is fast, 107 - 108 M-1s-1 for human Prx2. In addition, the high intracellular concentration of Prx positions them not only as good antioxidants but also as central players in redox signaling pathways. These biological functions can be affected by post-translational modifications that could alter the peroxidase activity and/or interaction with other proteins. In particular, inactivation by hyperoxidation of CP, which occurs when a second molecule of peroxide reacts with the CP in the sulfenic acid form, modulates their participation in redox signaling pathways. The higher sensitivity to hyperoxidation of some Prx has been related to the presence of structural motifs that disfavor disulfide formation at the active site, making the CP sulfenic acid more available for hyperoxidation or interaction with a redox protein target. We previously reported that treatment of human Prx2 with peroxynitrite results in tyrosine nitration, a post-translational modification on non-catalytic residues, yielding a more active peroxidase with higher resistance to hyperoxidation. In this work, studies on various mutants of hPrx2 confirm that the presence of the tyrosyl side-chain of Y193, belonging to the C-terminal YF motif of eukaryotic Prx, is necessary to observe the increase in Prx2 resistance to hyperoxidation. Moreover, our results underline the critical role of this structural motif on the rate of disulfide formation that determines the differential participation of Prx in redox signaling pathways.

Differential parameters between cytosolic 2-Cys peroxiredoxins, PRDX1 and PRDX2.

Peroxiredoxins are thiol-dependent peroxidases that function in peroxide detoxification and H2 O2 induced signaling. Among the six isoforms expressed in humans, PRDX1 and PRDX2 share 97% sequence similarity, 77% sequence identity including the active site, subcellular localization (cytosolic) but they hold different biological functions albeit associated with their peroxidase activity. Using recombinant human PRDX1 and PRDX2, the kinetics of oxidation and hyperoxidation with H2 O2 and peroxynitrite were followed by intrinsic fluorescence. At pH 7.4, the peroxidatic cysteine of both isoforms reacts nearly tenfold faster with H2 O2 than with peroxynitrite, and both reactions are orders of magnitude faster than with most protein thiols. For both isoforms, the sulfenic acids formed are in turn oxidized by H2 O2 with rate constants of ca 2 × 103 M-1 s-1 and by peroxynitrous acid significantly faster. As previously observed, a crucial difference between PRDX1 and PRDX2 is on the resolution step of the catalytic cycle, the rate of disulfide formation (11 s-1 for PRDX1, 0.2 s-1 for PRDX2, independent of the oxidant) which correlates with their different sensitivity to hyperoxidation. This kinetic pause opens different pathways on redox signaling for these isoforms. The longer lifetime of PRDX2 sulfenic acid allows it to react with other protein thiols to translate the signal via an intermediate mixed disulfide (involving its peroxidatic cysteine), whereas PRDX1 continues the cycle forming disulfide involving its resolving cysteine to function as a redox relay. In addition, the presence of C83 on PRDX1 imparts a difference on peroxidase activity upon peroxynitrite exposure that needs further study.

Arthroscopic Resection of Dorsal Wrist Ganglion: Results and Rate of Recurrence Over a Minimum Follow-up of 4 Years.

BACKGROUND: Dorsal wrist ganglia are the most common soft tissue tumor type of the upper limb. Surgical resection, open or arthroscopic, is one of the most frequent procedures performed by hand surgeons. This study sought to perform an objective evaluation of the outcomes of arthroscopic resection of dorsal wrist ganglia and their recurrence rates over 4 years. Patients treated with arthroscopic resection were expected to have favorable outcomes and low complication rates after 4 years of follow-up. METHODS: We evaluated 34 cases of dorsal wrist ganglia in patients who underwent arthroscopic resection. The patients were evaluated using the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH) outcome measure, visual analog scale (VAS) for pain, range of motion of the wrist, palmar grip strength, rates of recurrence, and complications. RESULTS: During the postoperative period, the QuickDASH score averaged 2.3 points, the mean residual pain by VAS was 0.54, full range of wrist movement was recovered by all patients, and the mean palmar grip strength was 29.4 kgf; there was 1 case with recurrence. There were no severe postoperative complications throughout the follow-up period. CONCLUSIONS: The outcomes, recurrence, and complications rates after 4 years of follow-up presented in this study support the use of arthroscopy as a treatment for dorsal wrist ganglion.

Photobiomodulation of a flowable matrix in a human skin ex vivo model demonstrates energy-based enhancement of engraftment integration and remodeling.

The use of dermal substitutes to treat skin defects such as ulcers has shown promising results, suggesting a potential role for skin substitutes for treating acute and chronic wounds. One of the main drawbacks with the use of dermal substitutes is the length of time from engraftment to graft take, plus the risk of contamination and failure due to this prolonged integration. Therefore, the use of adjuvant energy-based therapeutic modalities to augment and accelerate the rate of biointegration by dermal substitute engraftments is a desirable outcome. The photobiomodulation (PBM) therapy modulates the repair process, by stimulating cellular proliferation and angiogenesis. Here, we evaluated the effect of PBM on a collagen-glycosaminoglycan flowable wound matrix (FWM) in an ex vivo human skin wound model. PBM resulted in accelerated rate of re-epithelialization and organization of matrix as seen by structural arrangement of collagen fibers, and a subsequent increased expression of alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor A (VEGF-A) leading to an overall improved healing process. The use of PBM promoted a beneficial effect on the rate of integration and healing of FWM. We therefore propose that the adjuvant use of PBM may have utility in enhancing engraftment and tissue repair and be of value in clinical practice.

Isomeric effect on the properties of tetraplatinated porphyrins showing optimized phototoxicity for photodynamic therapy.

The design of new photosensitizers (PS) with improved properties is essential for the development of photodynamic therapy as an alternative therapeutic method. The conjugation of porphyrins, well known PS, with platinum(ii) complexes, potent anticancer agents, may achieve new compounds with synergistic treatment effects and no side-effects. In this study, we synthesized para and meta isomers of free-base meso-tetra(pyridyl)porphyrins complexed to [PtCl(bipy)]+ units, and investigated their photophysics in solution and in lipid membrane vesicles, correlating with cell incorporation and viability results obtained from in vitro experiments using HeLa cells. Both porphyrins showed high singlet oxygen quantum yields and phototoxicity at the nanomolar scale, with green light irradiation (522 nm) and under very low light dose (1 J cm-2). The porphyrins showed LC50 values of 25 nM (meta) and 50 nM (para), which is remarkable for such mild conditions. Moreover, the phototoxicity difference between the isomers could be assigned to the higher amphiphilicity of the meta substituted porphyrin, which leads to improved lipid membrane interaction and cellular uptake compared to the para isomer.

Wealth and cardiovascular health: a cross-sectional study of wealth-related inequalities in the awareness, treatment and control of hypertension in high-, middle- and low-income countries.

BACKGROUND: Effective policies to control hypertension require an understanding of its distribution in the population and the barriers people face along the pathway from detection through to treatment and control. One key factor is household wealth, which may enable or limit a household's ability to access health care services and adequately control such a chronic condition. This study aims to describe the scale and patterns of wealth-related inequalities in the awareness, treatment and control of hypertension in 21 countries using baseline data from the Prospective Urban and Rural Epidemiology study. METHODS: A cross-section of 163,397 adults aged 35 to 70 years were recruited from 661 urban and rural communities in selected low-, middle- and high-income countries (complete data for this analysis from 151,619 participants). Using blood pressure measurements, self-reported health and household data, concentration indices adjusted for age, sex and urban-rural location, we estimate the magnitude of wealth-related inequalities in the levels of hypertension awareness, treatment, and control in each of the 21 country samples. RESULTS: Overall, the magnitude of wealth-related inequalities in hypertension awareness, treatment, and control was observed to be higher in poorer than in richer countries. In poorer countries, levels of hypertension awareness and treatment tended to be higher among wealthier households; while a similar pro-rich distribution was observed for hypertension control in countries at all levels of economic development. In some countries, hypertension awareness was greater among the poor (Sweden, Argentina, Poland), as was treatment (Sweden, Poland) and control (Sweden). CONCLUSION: Inequality in hypertension management outcomes decreased as countries became richer, but the considerable variation in patterns of wealth-related inequality - even among countries at similar levels of economic development - underscores the importance of health systems in improving hypertension management for all. These findings show that some, but not all, countries, including those with limited resources, have been able to achieve more equitable management of hypertension; and strategies must be tailored to national contexts to achieve optimal impact at population level.

Prevalence of human papillomavirus types and variants and p16(INK4a) expression in head and neck squamous cells carcinomas in São Paulo, Brazil.

BACKGROUND: Human papillomavirus (HPV) prevalence in head and neck squamous cell carcinomas (HNSCC) diverges geographically. The reliability of using p16(INK4a) expression as a marker of viral infection is controversial in HNSCC. We evaluated HPV types and HPV-16 variants prevalence, and p16(INK4a) expression in HNSCC specimens provided by two different Institutions in São Paulo. METHODS: HPV DNA from formalin-fixed specimens was accessed by Inno-LiPA, HPV-16 variants by PCR-sequencing, and p16(INK4a) protein levels by immunohistochemistry. RESULTS: Overall, HPV DNA was detected among 19.4 % of the specimens (36/186). Viral prevalence was higher in the oral cavity (25.0 %, 23/92) then in other anatomical sites (oropharynx 14,3 %, larynx 13.7 %) when samples from both Institutions were analyzed together. HPV prevalence was also higher in the oral cavity when samples from both Institutions were analyzed separately. HPV-16 was the most prevalent type identified in 69.5 % of the HPV positive smaples and specimens were assigned into Asian-American (57.2 %) or European (42.8 %) phylogenetic branches. High expression of p16(INK4a) was more common among HPV positive tumors. CONCLUSION: Our results support a role for HPV-16 in a subset of HNSCC.

Purification of a recombinant glutathione transferase from the causative agent of hydatidosis, Echinococcus granulosus.

This practical class activity was designed to introduce students to recombinant protein expression and purification. The principal goal is to shed light on basic aspects concerning recombinant protein production, in particular protein expression, chromatography methods for protein purification, and enzyme activity as a tool to evaluate purity and conformation of the recombinant product. Herein, we describe the purification of a glutathione transferase from the human parasite Echinococcus granulosus (EgGST1), the causative agent of hydatidosis. EgGST1 is expressed fused to a histidine tag and is purified by immobilized metal affinity chromatography. Protein quantification based on direct (UV absorbance) and indirect (colorimetric) methods are used and discussed. A simple colorimetric assay is used to measure GST activity and special emphasis is put on how to use these measurements to follow protein purification yields, its enrichment and its correct folding along the purification process. EgGST1 is easily expressed with high yields, purified in absence of protease inhibitors and proved to be robust concerning enzyme activity and protein integrity on a 1 week practical activity.

Wealth and cardiovascular health: across-sectional study of wealth-related inequalities in the awareness, treatmentand control of hypertension in high-,middle- and low-income countries

Effective policies to control hypertension require an understanding of its distribution in the population and the barriers people face along the pathway from detection through to treatment and control. One key factor is household wealth, which may enable or limit a household’s ability to access health care services and adequately control such a chronic condition. This study aims to describe the scale and patterns of wealth-related inequalities in the awareness, treatment and control of hypertension in 21 countries using baseline data from the Prospective Urbanand Rural Epidemiology study. Methods: A cross-section of 163,397 adults aged 35 to 70 years were recruited from 661 urban and rural communities in selected low-, middle- and high-income countries (complete data for this analysis from 151,619 participants). Using blood pressure measurements, self-reported health and household data, concentration indices adjusted for age, sex and urban-rural location, we estimate the magnitude of wealth-related inequalities in thelevels of hypertension awareness, treatment, and control in each of the 21 country samples. Results: Overall, the magnitude of wealth-related inequalities in hypertension awareness, treatment, and control wasobserved to be higher in poorer than in richer countries. In poorer countries, levels of hypertension awareness and treatment tended to be higher among wealthier households; while a similar pro-rich distribution was observed forhypertension control in countries at all levels of economic development. In some countries, hypertension awarenesswas greater among the poor (Sweden, Argentina, Poland), as was treatment (Sweden, Poland) and control (Sweden)...

Monoparentalidade programada e reprodução assistida: da “produção independente” à utilização de sêmen póst mortem / Orogrammed “Single” Parenthood and Human Assisted Reproduction: from the“Independent Production” to the Utilization of Post Mortem Semen

A utilização das técnicas de reprodução assistida vem possibilitando, nas últimas décadas, a realização da vontade de exercer a parentalidade em diferentes contextos e situações, muito além da infertilidade. Aqui são elaboradas reflexões associadas à monoparentalidade buscada, não acidental, considerando contingências específicas, tais como a utilização de sêmen post mortem e a denominada produção independente, seja em indivíduos hétero ou homossexuais. Tais reflexões são eliciadas em virtude da prática clínica à luz da revisão de literatura e debruçam-se sobre as condições que favorecem essa busca, muitas vezes de caráter narcísico e que necessitam de uma escuta e uma interlocução privilegiada no atendimento clínico. (AU)

In the last decades, the use of assisted reproduction techniques has favored the fulfillment of parenthood desires indifferent contexts and situations, beyond infertility it self. This paper discusses issues related to programmed single parenthood eagerly sought in specific situations, such as the use of post mortem semen and the so-called “independentproduction” among hetero and homosexual individuals. This reflexion is brought by the authors’ clinical experienceand addresses the conditions that favor this perhaps narcissistic search, which needs a specialized hearing and exchangewithin the clinical context. (AU)

Monoparentalidade programada e reprodução assistida: da “produção independente” à utilização de sêmen póst mortem / Orogrammed “Single” Parenthood and Human Assisted Reproduction: from the“Independent Production” to the Utilization of Post Mortem Semen

A utilização das técnicas de reprodução assistida vem possibilitando, nas últimas décadas, a realização da vontade de exercer a parentalidade em diferentes contextos e situações, muito além da infertilidade. Aqui são elaboradas reflexões associadas à monoparentalidade buscada, não acidental, considerando contingências específicas, tais como a utilização de sêmen post mortem e a denominada produção independente, seja em indivíduos hétero ou homossexuais. Tais reflexões são eliciadas em virtude da prática clínica à luz da revisão de literatura e debruçam-se sobre as condições que favorecem essa busca, muitas vezes de caráter narcísico e que necessitam de uma escuta e uma interlocução privilegiada no atendimento clínico...

In the last decades, the use of assisted reproduction techniques has favored the fulfillment of parenthood desires indifferent contexts and situations, beyond infertility it self. This paper discusses issues related to programmed single parenthood eagerly sought in specific situations, such as the use of post mortem semen and the so-called “independentproduction” among hetero and homosexual individuals. This reflexion is brought by the authors’ clinical experienceand addresses the conditions that favor this perhaps narcissistic search, which needs a specialized hearing and exchangewithin the clinical context...

Nitration transforms a sensitive peroxiredoxin 2 into a more active and robust peroxidase.

Peroxiredoxins (Prx) are efficient thiol-dependent peroxidases and key players in the mechanism of H2O2-induced redox signaling. Any structural change that could affect their redox state, oligomeric structure, and/or interaction with other proteins could have a significant impact on the cascade of signaling events. Several post-translational modifications have been reported to modulate Prx activity. One of these, overoxidation of the peroxidatic cysteine to the sulfinic derivative, inactivates the enzyme and has been proposed as a mechanism of H2O2 accumulation in redox signaling (the floodgate hypothesis). Nitration of Prx has been reported in vitro as well as in vivo; in particular, nitrated Prx2 was identified in brains of Alzheimer disease patients. In this work we characterize Prx2 tyrosine nitration, a post-translational modification on a noncatalytic residue that increases its peroxidase activity and its resistance to overoxidation. Mass spectrometry analysis revealed that treatment of disulfide-oxidized Prx2 with excess peroxynitrite renders mainly mononitrated and dinitrated species. Tyrosine 193 of the YF motif at the C terminus, associated with the susceptibility toward overoxidation of eukaryotic Prx, was identified as nitrated and is most likely responsible for the protection of the peroxidatic cysteine against oxidative inactivation. Kinetic analyses suggest that tyrosine nitration facilitates the intermolecular disulfide formation, transforming a sensitive Prx into a robust one. Thus, tyrosine nitration appears as another mechanism to modulate these enzymes in the complex network of redox signaling.

Peroxiredoxins as preferential targets in H2O2-induced signaling.

Evidence has accumulated showing that hydrogen peroxide (H2O2) acts as a signaling molecule via oxidation of critical cysteine residues on target proteins. The reaction of H2O2 with thiols is thermodynamically favored, but its selectivity is imposed by differences in reaction kinetics. Previously proposed signal relaying mechanisms, such as the floodgate hypothesis and widespread protein sulfenylation, appear inconsistent with kinetic and diffusion considerations. Among all cellular thiols, the peroxidatic cysteines of peroxiredoxins (Prxs) represent preferential targets considering their high rate constants and their cellular abundance that place them as the first step in the H2O2-induced signaling pathways. The oxidized Prxs could transfer the signal either via thiol-disulfide redox reactions or through nonredox protein-protein interactions. Recent studies evidence Prxs interactions with protein tyrosine kinases and phosphatases, indicating a potential connection between redox and phosphorylation signaling pathways that does not need the direct reaction of H2O2 with phosphatase or kinase critical cysteines. Posttranslational modifications of Prxs have been observed in vivo (mainly overoxidation of cysteines and phosphorylation of threonines) that affect their peroxidase activity, redox state, and/or oligomeric structure, and likely impact on H2O2 signaling. More focus on kinetic data and redox-sensitive protein-protein interactions are needed to unravel the molecular mechanisms of H2O2 signaling.

Effects of microcurrent application alone or in combination with topical Hypericum perforatum L. and Arnica montana L. on surgically induced wound healing in Wistar rats.

OBJECTIVES: This study evaluated the wound healing activity of microcurrent application alone or in combination with topical Hypericum perforatum L. and Arnica montana L. on skin surgical incision surgically induced on the back of Wistar rats. DESIGN: The animals were randomly divided into six groups: (1) no intervention (control group); (2) microcurrent application (10 µA/2 min); (3) topical application of gel containing H. perforatum; (4) topical application of H. perforatum gel and microcurrent (10 µA/2 min); (5) topical application of gel containing A. montana; (6) topical application of A. montana gel and microcurrent (10 µA/2 min). Tissue samples were obtained on the 2nd, 6th and 10th days after injury and submitted to structural and morphometric analysis. RESULTS AND CONCLUSION: Differences in wound healing were observed between treatments when compared to the control group. Microcurrent application alone or combined with H. perforatum gel or A. montana gel exerted significant effects on wound healing in this experimental model in all of the study parameters (P<0.05) when compared to the control group with positive effects seen regarding newly formed tissue, number of newly formed blood vessels and percentage of mature collagen fibers. The morphometric data confirmed the structural findings. In conclusion, application of H. perforatum or A. montana was effective on experimental wound healing when compared to control, but significant differences in the parameters studied were only observed when these treatments were combined with microcurrent application.