Disyunción maxilar rápida asistida con microtornillos en pacientes en crecimiento con deficiencia maxilar transversal / Miniscrew assisted rapid maxillary expansion in growing patients with transverse maxillary deficiency

RESUMEN: Introducción: La disyunción maxilar rápida tradicional (RME) ha sido el tratamiento de elección para corregir la maloclusión secundaria a la deficiencia maxilar transversal. Debido a las complicaciones que pueden presentar los pacientes, se han desarrollado técnicas de disyunción maxilar asistida por microtornillos (MARPE). Sin embargo, aún no hay consenso respecto a los reales beneficios de la disyunción maxilar rápida asistida por microtornillos por sobre la disyunción tradicional en pacientes jóvenes y en crecimiento. Métodos: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. Resultados y conclusiones: Identificamos siete revisiones sistemáticas que en conjunto incluyeron seis estudios primarios, de los cuales todos corresponden a ensayos aleatorizados. Concluimos que: la disyunción maxilar rápida asistida por microtornillos (MARPE) probablemente disminuye la pérdida de hueso alveolar bucal y la resistencia de la vía aérea nasal en comparación a la disyunción maxilar rápida tradicional (RME) (certeza evidencia moderada). MARPE podría disminuir la inclinación dentaria y resultar en poca o nula diferencia en la percepción de dolor en comparación con RME (certeza de la evidencia baja). No es posible establecer con claridad si MARPE aumenta la expansión maxilar en comparación con RME, debido a que la certeza de la evidencia ha sido evaluada como muy baja.

ABSTRACT: Introduction: Traditional rapid maxillary expansion (RME) has been the gold-standard treatment to correct malocclusion secondary to transverse maxillary deficiency. Due to related complications, mini screw assisted maxillary expansion (MARPE) techniques have been developed. However, there is no consensus regarding the benefits of mini screw assisted maxillary expansion over traditional expansion in young and growing patients. Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. Results and conclusions: We identified seven systematic reviews including six studies overall, all of which were randomized trials. We concluded that mini screw maxillary expansion (MARPE) probably reduces buccal alveolar bone and nasal airway resistance compared to traditional rapid maxillary expansion (RME). MARPE may reduce dental inclination and result in little or no difference in pain perception compared to RME. We are uncertain whether MARPE improves maxillary expansion compared to RME, as the certainty of the evidence has been assessed as very low.

l-NIL prevents the ischemia and reperfusion injury involving TLR-4, GST, clusterin, and NFAT-5 in mice.

On renal ischemia-reperfusion (I/R) injury, recruitment of neutrophils during the inflammatory process promotes local generation of oxygen and nitrogen reactive species, which, in turn, are likely to exacerbate tissue damage. The mechanism by which inducible nitric oxide synthase (iNOS) is involved in I/R has not been elucidated. In this work, the selective iNOS inhibitor l- N6-(1-iminoethyl)lysine (l-NIL) and the NOS substrate l-arginine were employed to understand the role of NOS activity on the expression of particular target genes and the oxidative stress elicited after a 30-min of bilateral renal ischemia, followed by 48-h reperfusion in Balb/c mice. The main findings of the present study were that pharmacological inhibition of iNOS with l-NIL during an I/R challenge of mice kidney decreased renal injury, prevented tissue loss of integrity, and improved renal function. Several novel findings regarding the molecular mechanism by which iNOS inhibition led to these protective effects are as follows: 1) a prevention of the I/R-related increase in expression of Toll-like receptor 4 (TLR-4), and its downstream target, IL-1ß; 2) reduced oxidative stress following the I/R challenge; noteworthy, this study shows the first evidence of glutathione S-transferase (GST) inactivation following kidney I/R, a phenomenon fully prevented by iNOS inhibition; 3) increased expression of clusterin, a survival autophagy component; and 4) increased expression of nuclear factor of activated T cells 5 (NFAT-5) and its target gene aquaporin-1. In conclusion, prevention of renal damage following I/R by the pharmacological inhibition of iNOS with l-NIL was associated with the inactivation of proinflammatory pathway triggered by TLR-4, oxidative stress, renoprotection (autophagy inactivation), and NFAT-5 signaling pathway.

Abortion legislation, maternal healthcare, fertility, female literacy, sanitation, violence against women and maternal deaths: a natural experiment in 32 Mexican states.

OBJECTIVE: To test whether there is an association between abortion legislation and maternal mortality outcomes after controlling for other factors thought to influence maternal health. DESIGN: Population-based natural experiment. SETTING AND DATA SOURCES: Official maternal mortality data from 32 federal states of Mexico between 2002 and 2011. MAIN OUTCOMES: Maternal mortality ratio (MMR), MMR with any abortive outcome (MMRAO) and induced abortion mortality ratio (iAMR). INDEPENDENT VARIABLES: Abortion legislation grouped as less (n=18) or more permissive (n=14); constitutional amendment protecting the unborn (n=17); skilled attendance at birth; all-abortion hospitalisation ratio; low birth weight rate; contraceptive use; total fertility rates (TFR); clean water; sanitation; female literacy rate and intimate-partner violence. MAIN RESULTS: Over the 10-year period, states with less permissive abortion legislation exhibited lower MMR (38.3 vs 49.6; p<0.001), MMRAO (2.7 vs 3.7; p<0.001) and iAMR (0.9 vs 1.7; p<0.001) than more permissive states. Multivariate regression models estimating effect sizes (ß-coefficients) for mortality outcomes showed independent associations (p values between 0.001 and 0.055) with female literacy (ß=-0.061 to -1.100), skilled attendance at birth (ß=-0.032 to -0.427), low birth weight (ß=0.149 to 2.166), all-abortion hospitalisation ratio (ß=-0.566 to -0.962), clean water (ß=-0.048 to -0.730), sanitation (ß=-0.052 to -0.758) and intimate-partner violence (ß=0.085 to 0.755). TFR showed an inverse association with MMR (ß=-14.329) and MMRAO (ß=-1.750) and a direct association with iAMR (ß=1.383). Altogether, these factors accounted for (R(2)) 51-88% of the variance among states in overall mortality rates. No statistically independent effect was observed for abortion legislation, constitutional amendment or other covariates. CONCLUSIONS: Although less permissive states exhibited consistently lower maternal mortality rates, this finding was not explained by abortion legislation itself. Rather, these differences were explained by other independent factors, which appeared to have a more favourable distribution in these states.

Fundamental discrepancies in abortion estimates and abortion-related mortality: A reevaluation of recent studies in Mexico with special reference to the International Classification of Diseases.

In countries where induced abortion is legally restricted, as in most of Latin America, evaluation of statistics related to induced abortions and abortion-related mortality is challenging. The present article reexamines recent reports estimating the number of induced abortions and abortion-related mortality in Mexico, with special reference to the International Classification of Diseases (ICD). We found significant overestimations of abortion figures in the Federal District of Mexico (up to 10-fold), where elective abortion has been legal since 2007. Significant overestimation of maternal and abortion-related mortality during the last 20 years in the entire Mexican country (up to 35%) was also found. Such overestimations are most likely due to the use of incomplete in-hospital records as well as subjective opinion surveys regarding induced abortion figures, and due to the consideration of causes of death that are unrelated to induced abortion, including flawed denominators of live births. Contrary to previous publications, we found important progress in maternal health, reflected by the decrease in overall maternal mortality (30.6%) from 1990 to 2010. The use of specific ICD codes revealed that the mortality ratio associated with induced abortion decreased 22.9% between 2002 and 2008 (from 1.48 to 1.14 deaths per 100,000 live births). Currently, approximately 98% of maternal deaths in Mexico are related to causes other than induced abortion, such as hemorrhage, hypertension and eclampsia, indirect causes, and other pathological conditions. Therefore, only marginal or null effects would be expected from changes in the legal status of abortion on overall maternal mortality rates. Rather, maternal health in Mexico would greatly benefit from increasing access to emergency and specialized obstetric care. Finally, more reliable methodologies to assess abortion-related deaths are clearly required.

[Overestimation of the ocurrence of induced abortions in Colombia and other Latinoamerican countries]. / Sobrestimación del aborto inducido en Colombia y otros países latinoamericanos.

Recently, the Guttmacher Institute estimated a number of 400,400 clandestine abortions for Colombia. Because of the strong implications that such brief could have in different areas of interest, a full revision of the methodology of estimation was performed. The methodology used by the Guttmacher Institute was as follows: first, the authors estimated the losses from spontaneous and induced abortions from the opinion of 289 subjects who work in an equal number of Colombian health institutions through the opinion survey entitled "Health Facilities Survey". Subsequently, an expansive multiplier (x3, x4, x5, etc.) was applied to the numbers obtained by this survey that also emerges from a subjective opinion of another 102 respondents of the "Health Professional Survey" selected by convenience. There is no objective data based on real vital events, the whole estimate is based on imagining/numbers underlying mere opinions. Even as public opinion survey, the sampling technique introduced serious selection bias in the gathering of information. Valid epidemiological methods using standardized rates, choosing the paradigmatic cases of Chile and Spain as standard populations, it was observed that Guttmacher Institute methodology overestimates more than 9 times the complications due to induced abortion in hospital discharges and more than 18 times the total number of induced abortions. In other Latin American countries where the same methodology was applied including Argentina, Brazil, Chile, Mexico, Peru, Guatemala, and Dominican Republic, the number of induced abortions was also largely overestimated. These results call for caution with this type of reports that alarm public opinion.

Microsomal oxidative damage promoted by acetaminophen metabolism.

Adverse reactions of acetaminophen have been associated to oxidative stress, which may be elicited by reactive oxygen species (ROS) and/or production of the metabolite NAPQI. Both phenomena would arise through the activity of liver cytochrome P450 (CYP450) system, but their contribution to this oxidative stress is yet to be clarified. A NADPH oxidase activity has been proposed in rat liver microsomes. This activity may be due to the presence of NAD(P)H oxidase (NOX) isoforms in liver endoplasmic reticulum. Both NOX and the CYP450 system activities can catalyze ROS generation using NADPH as a cofactor. Therefore, acetaminophen biotransformation, which requires NADPH, may promote ROS generation through either activity or both. To discriminate between these possibilities, rat liver microsomes were incubated with acetaminophen and NADPH in the presence or absence of specific inhibitors. Incubation with NADPH and acetaminophen elicited lipid peroxidation and decreased thiol content and glutathione-S-transferase (GST) activity. The NOX inhibitors apocynin and plumbagin prevented all these phenomena but the decrease in thiol content. In contrast, this decrease was completely prevented by the specific CYP450 system inhibitor SKF-525A. These data suggest that ROS generation following incubation of microsomes with acetaminophen and NADPH appears to be mainly caused by a NOX activity. In light of these data, toxicity of acetaminophen is discussed.

Iron and glutathione at the crossroad of redox metabolism in neurons.

Neurons, as non-dividing cells, encounter a myriad of stressful conditions throughout their lifespan. In particular, there is increasing evidence that iron progressively accumulates in the brain with age and that iron induced oxidative stress is the cause of several forms of neurodegeneration. Here, we review recent evidence that gives support to the following notions: 1) neuronal iron accumulation leads to oxidative stress and cell death; 2) neuronal survival to iron accumulation associates with decreased expression of the iron import transporter DMT1 and increased expression of the efflux transporter IREG1; and 3) the adaptive process of neurons towards iron-induced oxidative stress includes a marked increase in both the expression of the catalytic subunit of gamma glutamate-cysteine ligase and glutathione. These findings may help to understand aging-related neurodegeneration hallmarks: oxidative damage, functional impairment and cell death.

Iron and glutathione at the crossroad of redox metabolism in neurons

Neurons, as non-dividing cells, encounter a myriad of stressful conditions throughout their lifespan. In particular, there is increasing evidence that iron progressively accumulates in the brain with age and that iron-induced oxidative stress is the cause of several forms of neurodegeneration. Here, we review recent evidence that gives support to the following notions: 1) neuronal iron accumulation leads to oxidative stress and cell death; 2) neuronal survival to iron accumulation associates with decreased expression of the iron import transporter DMT1 and increased expression of the efflux transporter IREG1; and 3) the adaptive process of neurons towards iron-induced oxidative stress includes a marked increase in both the expression of the catalytic subunit of gamma glutamate-cysteine ligase and glutathione. These findings may help to understand aging-related neurodegeneration hallmarks: oxidative damage, functional impairment and cell death.

Effects of S-glutathionylation and S-nitrosylation on calmodulin binding to triads and FKBP12 binding to type 1 calcium release channels.

This study shows that the combination of glutathione (GSH) plus hydrogen peroxide (H2O2) promotes the S-glutathionylation of ryanodine receptor type 1 (RyR1) Ca2+ release channels, and confirms their joint S-glutathionylation and S-nitrosylation by S-nitrosoglutathione (GSNO). In addition, we show that 35S-labeled 12-kDa FK506-binding protein ([35S]FKBP12) bound with a Kd of 13.1 nM to RyR1 present in triads or heavy sarcoplasmic reticulum vesicles; RyR1 S-nitrosylation by NOR-3 or GSNO, but not S-glutathionylation, specifically increased by four- to fivefold this Kd value. RyR1 redox modifications also increased the Kd of [35S]calmodulin binding to triads without affecting Bmax. RyR1 S-glutathionylation (induced by GSH plus H2O2) or RyR1 S-nitrosylation (produced by NOR-3) increased by approximately six- or twofold, respectively, the Kd of apocalmodulin (apoCaM) or Ca2+-calmodulin (CaCaM) binding to triads. Likewise, the combined S-glutathionylation and S-nitrosylation of RyR1 induced by GSNO increased by fourfold the Kd of CaCaM binding to triads and abolished apoCaM binding. As both FKBP12 and CaCaM inhibit RyR1, decreased FKBP12 binding to RyR1 and/or decreased CaCaM binding to either RyR1 or dihydropyridine receptor in triad preparations may cause the reported enhanced activation of Ca2+-induced Ca2+ release kinetics mediated by S-glutathionylation/S-nitrosylation. We discuss possible consequences of these redox modifications on RyR1-mediated Ca2+ release in physiological or pathological conditions.

Microsomal UDP-glucuronyltransferase in rat liver: oxidative activation.

Activation of microsomal UDP-glucuronyltransferase (UDPGT) activity by treatment of hepatic microsomes with either detergents or Fe(3+)/ascorbate pro-oxidant system has been reported; however, definite mechanisms underlying these effects have not been clarified. In this work, we characterize Fe(3+)/ascorbate-induced activation of UDPGT activity prior to solubilization with Triton X-100 and after the oxidation process provoked the solubilization of the enzyme. We observed a time-dependent increase in UDPGT activity up to 20 min. incubation of the microsomes with Fe(3+)/ascorbate (3-times); after 20 min. incubation, however, we observed a time-dependent decrease in this activity to basal levels after 4 hr incubation. Treatment of microsomes with 0.1% Triton X-100 (5 min.) lead to a similar increase in UDPGT activity; higher detergent concentrations produced a dose-dependent decrease in this activity to basal levels with 1% Triton X-100. Interestingly, UDPGT activity was susceptible to activation only when associated to microsomal membranes and the loss of activation correlated with the solubilization of this activity. UDPGT activation by either Fe(3+)/ascorbate or Triton X-100 was correlated with an increase in p-nitrophenol apparent K(m) and V(max) values. This activation was prevented or reversed by the reducing agents glutathione, cysteine or dithiothreitol when it was induced by the Fe(3+)/ascorbate. Furthermore, the latter provoked a significant decrease in microsomal thiol content, effect not observed after treatment with Triton X-100. Our results suggest that the main mechanism responsible for Fe(3+)/ascorbate-induced UDPGT activation is likely to be the promotion of protein sulfhydryl oxidation; this mechanism appears to be different from detergent-induced UDPGT activation.

Possible mechanisms underlying copper-induced damage in biological membranes leading to cellular toxicity.

It is generally accepted that copper toxicity is a consequence of the generation of reactive oxygen species (ROS) by copper ions via Fenton or Haber-Weiss reactions. Copper ions display high affinity for thiol and amino groups occurring in proteins. Thus, specialized proteins containing clusters of these groups transport and store copper ions, hampering their potential toxicity. This mechanism, however, may be overwhelmed under copper overloading conditions, in which copper ions may bind to thiol groups occurring in proteins non-related to copper metabolism. In this study, we propose that indiscriminate copper binding may lead to damaging consequences to protein structure, modifying their biological functions. Therefore, we treated liver subcellular membrane fractions, including microsomes, with Cu2+ ions either alone or in the presence of ascorbate (Cu2+/ascorbate); we then assayed both copper-binding to membranes, and microsomal cytochrome P450 oxidative system and GSH-transferase activities. All assayed sub-cellular membrane fractions treated with Cu2+ alone displayed Cu2+-binding, which was significantly increased in the presence of Zn2+, Hg2+, Cd2+, Ag+1 and As3+. Treatment of microsomes with Cu2+ in the microM range decreased the microsomal thiol content; in the presence of ascorbate, Cu2+ added in the nM concentrations range induced a significant microsomal lipoperoxidation; noteworthy, increasing Cu2+ concentration to > or =50 microM led to non-detectable lipoperoxidation levels. On the other hand, microM Cu2+ led to the inhibition of the enzymatic activities tested to the same extent in either presence or absence of ascorbate. We discuss the possible significance of indiscriminate copper binding to thiol proteins as a possible mechanism underlying copper-induced toxicity.

S-glutathionylation decreases Mg2+ inhibition and S-nitrosylation enhances Ca2+ activation of RyR1 channels.

We have analyzed the effects of the endogenous redoxactive agents S-nitrosoglutathione and glutathione disulfide, and the NO donor NOR-3, on calcium release kinetics mediated by ryanodine receptor channels. Incubation of triad-enriched sarcoplasmic reticulum vesicles isolated from mammalian skeletal muscle with these three agents elicits different responses. Glutathione disulfide significantly reduces the inhibitory effect of Mg2+ without altering Ca2+ activation of release kinetics, whereas NOR-3 enhances Ca2+ activation of release kinetics without altering Mg2+ inhibition. Incubation with S-nitrosoglutathione produces both effects; it significantly enhances Ca2+ activation of release kinetics and diminishes the inhibitory effect of Mg2+ on this process. Triad incubation with [35S]nitrosoglutathione at pCa 5 promoted 35S incorporation into 2.5 cysteine residues per channel monomer; this incorporation decreased significantly at pCa 9. These findings indicate that S-nitrosoglutathione supports S-glutathionylation as well as the reported S-nitrosylation of ryanodine receptor channels (Sun, J., Xu, L., Eu, J. P., Stamler, J. S., and Meissner, G. (2003) J. Biol. Chem. 278, 8184-8189). The combined results suggest that S-glutathionylation of specific cysteine residues can modulate channel inhibition by Mg2+, whereas S-nitrosylation of different cysteines can modulate the activation of the channel by Ca2+. Possible physiological and pathological implications of the activation of skeletal Ca2+ release channels by endogenous redox species are discussed.

Redox regulation of calcium release in skeletal and cardiac muscle.

In skeletal and cardiac muscle cells, specific isoforms of the Ryanodine receptor channels mediate Ca2+ release from the sarcoplasmic reticulum. These channels are highly susceptible to redox modifications, which regulate channel activity. In this work, we studied the effects of Ca2+ (endogenous agonist) and Mg2+ (endogenous inhibitor) on the kinetics of Ca2+ release from sarcoplasmic reticulum vesicles isolated from skeletal or cardiac mammalian muscle. Native skeletal vesicles exhibited maximal stimulation of release kinetics by 10-20 microM [Ca2+], whereas in native cardiac vesicles, maximal stimulation of release required only 1 microM [Ca2+]. In 10 microM [Ca2+], free [Mg2+] < 0.1 mM produced marked inhibition of release from skeletal vesicles but free [Mg2+] < or = 0.8 mM did not affect release from cardiac vesicles. Incubation of skeletal or cardiac vesicles with the oxidant thimerosal increased their susceptibility to stimulation by Ca2+ and decreased the inhibitory effect of Mg2+ in skeletal vesicles. Sulfhydryl-reducing agents fully reversed the effects of thimerosal. The endogenous redox species, glutathione disulfide and S-nitrosoglutathione, also stimulated release from skeletal sarcoplasmic reticulum vesicles. In 10 microM [Ca2+], 35S-nitrosoglutathione labeled a protein fraction enriched in release channels through S-glutathiolation. Free [Mg2+] 1 mM or decreasing free [Ca2+] to the nM range prevented this reaction. Possible physiological and pathological consequences of redox modification of release channels on Ca2+ signaling in heart and muscle cells are discussed.

Redox regulation of calcium release in skeletal and cardiac muscle

In skeletal and cardiac muscle cells, specific isoforms of the Ryanodine receptor channels mediate Ca2+ release from the sarcoplasmic reticulum. These channels are highly susceptible to redox modifications, which regulate channel activity. In this work, we studied the effects of Ca2+ (endogenous agonist) and Mg2+ (endogenous inhibitor) on the kinetics of Ca2+ release from sarcoplasmic reticulum vesicles isolated from skeletal or cardiac mammalian muscle. Native skeletal vesicles exhibited maximal stimulation of release kinetics by 10-20 microM [Ca2+], whereas in native cardiac vesicles, maximal stimulation of release required only 1 microM [Ca2+]. In 10 microM [Ca2+], free [Mg2+] < 0.1 mM produced marked inhibition of release from skeletal vesicles but free [Mg2+] < or = 0.8 mM did not affect release from cardiac vesicles. Incubation of skeletal or cardiac vesicles with the oxidant thimerosal increased their susceptibility to stimulation by Ca2+ and decreased the inhibitory effect of Mg2+ in skeletal vesicles. Sulfhydryl-reducing agents fully reversed the effects of thimerosal. The endogenous redox species, glutathione disulfide and S-nitrosoglutathione, also stimulated release from skeletal sarcoplasmic reticulum vesicles. In 10 microM [Ca2+], 35S-nitrosoglutathione labeled a protein fraction enriched in release channels through S-glutathiolation. Free [Mg2+] 1 mM or decreasing free [Ca2+] to the nM range prevented this reaction. Possible physiological and pathological consequences of redox modification of release channels on Ca2+ signaling in heart and muscle cells are discusse