Dietary protein restriction throughout intrauterine and postnatal life results in potentially beneficial myocardial tissue remodeling in the adult mouse heart.

Diet composition impacts metabolic and cardiovascular health with high caloric diets contributing to obesity related disorders. Dietary interventions such as caloric restriction exert beneficial effects in the cardiovascular system, but alteration of which specific nutrient is responsible is less clear. This study investigates the effects of a low protein diet (LPD) on morphology, tissue composition and function of the neonatal and adult mouse heart. Mice were subjected to LPD (8.8% protein) or standard protein diet (SPD, 22% protein) throughout intrauterine and postnatal life. At birth LPD female but not male offspring exhibit reduced body weight whereas heart weight was unchanged in both sexes. Cardiomyocyte cross sectional area was increased in newborn LPD females compared to SPD, whereas proliferation, cellular tissue composition and vascularization were unaffected. Adult female mice on LPD exhibit reduced body weight but normal heart weight compared to SPD controls. Echocardiography revealed normal left ventricular contractility in LPD animals. Histology showed reduced interstitial fibrosis, lower cardiomyocyte volume and elevated numbers of cardiomyocyte and non-myocyte nuclei per tissue area in adult LPD versus SPD myocardium. Furthermore, capillary density was increased in LPD hearts. In conclusion, pre- and postnatal dietary protein restriction in mice causes a potentially beneficial myocardial remodeling.

Prenatal Mechanistic Target of Rapamycin Complex 1 (m TORC1) Inhibition by Rapamycin Treatment of Pregnant Mice Causes Intrauterine Growth Restriction and Alters Postnatal Cardiac Growth, Morphology, and Function.

BACKGROUND: Fetal growth impacts cardiovascular health throughout postnatal life in humans. Various animal models of intrauterine growth restriction exhibit reduced heart size at birth, which negatively influences cardiac function in adulthood. The mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient and growth factor availability with cell growth, thereby regulating organ size. This study aimed at elucidating a possible involvement of mTORC1 in intrauterine growth restriction and prenatal heart growth. METHODS AND RESULTS: We inhibited mTORC1 in fetal mice by rapamycin treatment of pregnant dams in late gestation. Prenatal rapamycin treatment reduces mTORC1 activity in various organs at birth, which is fully restored by postnatal day 3. Rapamycin-treated neonates exhibit a 16% reduction in body weight compared with vehicle-treated controls. Heart weight decreases by 35%, resulting in a significantly reduced heart weight/body weight ratio, smaller left ventricular dimensions, and reduced cardiac output in rapamycin- versus vehicle-treated mice at birth. Although proliferation rates in neonatal rapamycin-treated hearts are unaffected, cardiomyocyte size is reduced, and apoptosis increased compared with vehicle-treated neonates. Rapamycin-treated mice exhibit postnatal catch-up growth, but body weight and left ventricular mass remain reduced in adulthood. Prenatal mTORC1 inhibition causes a reduction in cardiomyocyte number in adult hearts compared with controls, which is partially compensated for by an increased cardiomyocyte volume, resulting in normal cardiac function without maladaptive left ventricular remodeling. CONCLUSIONS: Prenatal rapamycin treatment of pregnant dams represents a new mouse model of intrauterine growth restriction and identifies an important role of mTORC1 in perinatal cardiac growth.

Absence of interdental papilla ­ Systematic review of available therapeutic modalities / Ausência de papila interdental ­ revisão sistemática sobre as modalidades terapêuticas disponíveis

The objective of the present study was to conduct a systematic review of the treatment alternatives for the absence of interdental papilla (AIP), a clinical situation that can have aesthetic and phonetic impacts. A search for original articles, in humans, reporting more than one case, without language restrictions, dealing with therapeutic alternatives for AIP, was conducted in the databases of MEDLINE and EMBASE. The strategy included [("interdental papilla" OR "black triangles" OR "open gingival embrasure") AND ("treatment" OR "therapy" OR "reconstruction")] up to the year of 2010, resulting in seven studies being included. One study was found upon checking the reference lists and was added, bringing the total to 8 studies. The sample size ranged from two to 19 participants. Six of the eight studies used periodontal surgical techniques and fi ve associated the subepithelial connective tissue graft. Two studies treated AIP with reticulated hyaluronic acid gel. The follow-up time ranged from four to 24 months. The results, in relation to the interdental space area, ranged from 43% to 100% of fi lling and the reduction of the distance between the contact point and the tip of the papilla ranged from 0.73 to 2.8 mm. Two studies did not describe the results numerically. It was concluded that the therapeutic results presented by the authors were positive. However, it is necessary to take into consideration that the designs of the studies included here have a weak capacity for generating scientifi c evidence. As studies with a randomized clinical trial design are not conducted to respond to this clinical question, the results of the present study should be used with caution.

O objetivo deste estudo foi realizar uma revisão sistemática sobre as alternativas de tratamento da ausência da papila interdental (API), situação clínica que pode trazer impactos estéticos e fonéticos. Uma busca por artigos originais, em humanos, apresentando mais de 1 caso, sem restrição de idiomas, que tratassem sobre alternativas terapêuticas para a API foi realizada nas bases de dados Pubmed e Embase. A estratégia incluiu: [("interdental papilla" OR "black triangles" OR "open gingival embrasure") AND ("treatment" OR "therapy" OR "reconstruction")] a partir do ano de 2010, resultando em sete estudos incluídos. Um estudo foi encontrado na verifi cação das listas de referências e adicionado, totalizando 8 estudos. O tamanho amostral variou de dois a 19 participantes. Seis dos oito estudos utilizaram técnicas cirúrgicas periodontais e cinco associaram o enxerto conjuntivo subepitelial. Dois estudos trataram a API com gel de ácido hialurônico reticulado. O tempo de acompanhamento variou de quatro a 24 meses. Os resultados em relação ao espaço/área interdental variaram de 43 a 100% de preenchimento e a redução da distância entre o ponto de contato e a ponta da papila variou de 0,73 a 2,8 mm. Dois estudos não descreveram numericamente os resultados. Conclui-se que os resultados terapêuticos apresentados pelos autores foram positivos. Entretanto, é preciso levar em consideração que o delineamento dos estudos incluídos tem fraca capacidade de gerar evidência científi ca. Enquanto estudos com delineamento do tipo ensaio clínico randomizado não sejam realizados para responder essa pergunta clínica, os resultados do presente estudo devem ser utilizados com cautela.

Impaired myocardial development resulting in neonatal cardiac hypoplasia alters postnatal growth and stress response in the heart.

AIMS: Foetal growth has been proposed to influence cardiovascular health in adulthood, a process referred to as foetal programming. Indeed, intrauterine growth restriction in animal models alters heart size and cardiomyocyte number in the perinatal period, yet the consequences for the adult or challenged heart are largely unknown. The aim of this study was to elucidate postnatal myocardial growth pattern, left ventricular function, and stress response in the adult heart after neonatal cardiac hypoplasia in mice. METHODS AND RESULTS: Utilizing a new mouse model of impaired cardiac development leading to fully functional but hypoplastic hearts at birth, we show that myocardial mass is normalized until early adulthood by accelerated physiological cardiomyocyte hypertrophy. Compensatory hypertrophy, however, cannot be maintained upon ageing, resulting in reduced organ size without maladaptive myocardial remodelling. Angiotensin II stress revealed aberrant cardiomyocyte growth kinetics in adult hearts after neonatal hypoplasia compared with normally developed controls, characterized by reversible overshooting hypertrophy. This exaggerated growth mainly depends on STAT3, whose inhibition during angiotensin II treatment reduces left ventricular mass in both groups but causes contractile dysfunction in developmentally impaired hearts only. Whereas JAK/STAT3 inhibition reduces cardiomyocyte cross-sectional area in the latter, it prevents fibrosis in control hearts, indicating fundamentally different mechanisms of action. CONCLUSION: Impaired prenatal development leading to neonatal cardiac hypoplasia alters postnatal cardiac growth and stress response in vivo, thereby linking foetal programming to organ size control in the heart.

Developmental defects and seedling lethality in apyrase AtAPY1 and AtAPY2 double knockout mutants.

Previously it was shown that the Arabidopsis apyrase genes AtAPY1 and AtAPY2 are crucial for male fertility because mutant pollen (apy1-1; apy2-1) with T-DNA insertions in both genes could not germinate (Steinebrunner et al. (2003) Plant Physiol. 131: 1638-1647). In this study, pollen germination was restored and apyrase T-DNA double knockouts (DKO) apy1-1/apy1-1; apy2-1/apy2-1 were generated by complementation with AtAPY2 under the control of a pollen-specific promoter. The DKO phenotype displayed developmental defects including the lack of functional root and shoot meristems. In cotyledons, morphogenetic and patterning abnormalities were apparent, e.g., unlobed pavement cells and stomatal clusters. Another set of lines was created which carried either AtAPY1 or AtAPY2 under a dexamethasone-(DEX)-inducible promoter as an additional transgene to the pollen-specific gene construct. Application of DEX did not reverse the DKO phenotype to wild-type, but some inducible lines exhibited less severe defects even in the absence of the inducer, probably due to some background expression. However, even these DKO mutants were seedling-lethal and shared other defects regarding cell division, cell expansion and stomatal patterning. Taken together, the defects in the DKO mutants demonstrate that AtAPY1 and AtAPY2 are essential for normal plant development.