Influence of intermittent fasting on myocardial infarction-induced cardiac remodeling.

BACKGROUND: Information on the role of intermittent fasting (IF) on pathologic cardiac remodeling is scarce. We compared the effects of IF before and after myocardial infarction (MI) on rat cardiac remodeling and survival. METHODS: Wistar rats were intermittently fasted (food available every other day) or fed ad libitum for 12 weeks and then divided into three groups: AL - fed ad libitum; AL/IF - fed AL before MI and IF after MI; and IF - fed IF before and after MI. Echocardiogram was performed before MI and 2 and 12 weeks after surgery. Isolated hearts were evaluated in Langendorff preparations. RESULTS: Before surgery, body weight (BW) was lower in IF than AL. Final BW was lower in AL/IF and IF than AL. Perioperative mortality did not change between AL (31.3%) and IF (27.3%). Total mortality was lower in IF than AL. Before surgery, echocardiographic parameters did not differ between groups. Two weeks after surgery, MI size did not differ between groups. Twelve weeks after MI, left ventricular (LV) diastolic posterior wall thickness was lower in AL/IF and IF than AL. The percentage of variation of echocardiographic parameters between twelve and two weeks showed that MI size decreased in all groups and the reduction was higher in IF than AL/IF. In Langendorff preparations, LV volume at zero end-diastolic pressure (V0; AL: 0.41 ± 0.05; AL/IF: 0.34 ± 0.06; IF: 0.28 ± 0.05 mL) and at 25 mmHg end-diastolic pressure (V25; AL: 0.61 ± 0.05; AL/IF: 0.54 ± 0.07; IF: 0.44 ± 0.06 mL) was lower in AL/IF and IF than AL and V25 was lower in IF than AL/IF. V0/BW ratio was lower in IF than AL and LV weight/V0 ratio was higher in IF than AL. Myocyte diameter was lower in AL/IF and IF than AL (AL: 17.3 ± 1.70; AL/IF: 15.1 ± 2.21; IF: 13.4 ± 1.49 µm). Myocardial hydroxyproline concentration and gene expression of ANP, Serca 2a, and α- and ß-myosin heavy chain did not differ between groups. CONCLUSION: Intermittent fasting initiated before or after MI reduces myocyte hypertrophy and LV dilation. Myocardial fibrosis and fetal gene expression are not modulated by feeding regimens. Benefit is more evident when intermittent fasting is initiated before rather than after MI.

Proteomic profile of root canal contents in teeth with post-treatment endodontic disease.

AIM: To characterize the proteome of 20 root canals in teeth with post-treatment endodontic disease using mass spectrometry and to correlate the identified proteins with clinical features. METHODOLOGY: Twenty patients with radiographic evidence of apical periodontitis and need for root canal re-treatment were selected. Samples from the root canal contents were collected and processed using two-dimensional capillary nano-flow liquid chromatography and electrospray ionization tandem mass spectrometry. The acquired spectra were separately searched against specific protein database. The results obtained were analysed using descriptive statistics. Additionally, Pearson's chi-square test or one-sided Fisher's exact test, as appropriate, was chosen to examine the null hypothesis that there is no relationship between each clinical feature and the presence of specific microbial or human proteins. Significance levels were set at 5% (P < 0.05). RESULTS: A total of 1153 human and 720 microbial UniProt accession numbers corresponding to proteins were recovered. The greater prevalence of proteins was related to biological functions, such as cellular and metabolic processes. A considerable number of microbial proteins with clinical relevance functions, such as pathogenesis/virulence, proteolysis, cell adhesion and drug resistance, were detected. Common endodontic pathogens related to post-treatment endodontic disease such as Enterococcus spp., Propionibacterium spp. and Streptococcus spp. were associated with 23, 40 and 94 distinct proteins, respectively. As for human proteins, many factors related to the immune system process were detected. No significant correlations were found between microbial and human proteins and the clinical features investigated (P > 0.05). CONCLUSIONS: A considerable number of microbial and human proteins were identified using proteomic analyses, being mainly related to processes indicating cell viability. No significant correlation was found between proteins and clinical features. These findings suggest a network of important microbial pathogenic functions that may be responsible for the host immune system response.

Spatial distribution and seasonality of ichthyoplankton and anthropogenic debris in a river delta in the Caribbean Sea.

Temporal changes in larval fish species composition and abundance compared with other components of the seston are described in four estuarine habitats in the Atrato Delta, Colombia. In comparison with zooplankton, fish larvae and egg density and anthropogenic debris abundance were low in the South Atrato Delta. Transparency, water temperature and chlorophyll a were the major factors influencing the spatiotemporal distribution of ichthyoplankton in the delta. The most abundant fish larvae were Astyanax sp. 1, Anchovia clupeoides, Cetengraulis edentulus, Anchoa sp., Bathygbius curacao, Dormitator maculatus, Hyporhamphus sp., Atherinella blackburni, Gobiosoma sp. 1 and Menticirrhus americanus (92·8% of total abundance). Spatial temporal analysis shows that in this delta, shrub (arracachal) and grass (eneal) habitats are important for freshwater and estuarine species, whilst mudflat and mangrove are important for estuarine species and estuarine-marine species, since most flexion and post-flexion stages of these species were found there. Anthropogenic debris density never surpassed the total ichthyoplankton density, but was ubiquitous. Shrub and mangrove habitats had higher densities of anthropogenic debris, since these are flood-stem habitats that trap solids.

Fasting heat production of Saanen and Anglo Nubian goats measured using open-circuit facemask respirometry.

This study aimed to establish the heat production (HP) of Saanen and Anglo Nubian goats at absorptive (feeding) and at post-absorptive (fasting) statuses to determine the adequate period of fasting required for the measurement of basal metabolism. Gas exchange was recorded via open-circuit facemask respirometry. Six non-lactating and non-pregnant goats of each breed, Saanen (49.2 ± 3.2 kg of body weight, BW) and Anglo Nubian (64.0 ± 3.0 kg BW), were placed in individual pens with ad libitum access to the same total mixed ration. After a 3-day feeding period, the animals were subjected to fasting (no feed), and the gas exchange measurement was performed for 30 min at 0, 12, 20, 36, 44, 60 and 68 h after fasting. The daily HP of the Saanen and Anglo Nubian goats averaged 557.4 ± 38.7 and 357.1 ± 35.3 kJ/kg0.75  BW day respectively. During fasting, the methane production decreased exponentially in both breeds, and the critical time when methane production was statistically equal to zero was at 31 h of fasting for the Saanen goats and at 40 h for the Anglo Nubian goats. The daily HP and respiratory exchange rate during fasting decreased up to 60 h. Taken together, our results suggest that the ideal period to measure fasting heat production (FHP) for goats fed at maintenance levels should be between 40 h and 60 h of fasting. Consequently, the daily FHP, after 60 h of fasting, of Saanen and Anglo Nubian goats was 183.3 ± 16.3 and 211.1 ± 11.5 kJ/kg0.75  BW day respectively. The results presented herein are relevant for future studies of energy metabolism in goats.

Homology modeling and molecular dynamics of ß-defensin II variants in Amazonian sheep.

ß-defensins are capable of creating pores in the bacterial membrane. In this study, we aim to determine the structure of 3 different sheep ß-defensin 2 (SBD-2) sequences by molecular modeling. A herd of 47 sheep from the Centre for Ovine and Caprine Research of Pará was selected for this investigation. The AA, AG, and GG alleles were found on ß-defensin sequences. We used homology modeling and molecular dynamic simulations to generate 3D models of peptides and they were successfully validated. The proteins are structurally very similar to classic defensins composed of 3 ß-sheets and 3 disulfide bonds. Variations in the organization of the tertiary structure and distribution of charged residues were found between AA, AG, and GG alleles. In this study, we were able to characterize and show the structure of 3 SBD-2 gene variants for the first time in Amazonian sheep. Results demonstrated that these variants are similar in structures to classic ß-defensins, but contain more positives charges, which may indicate an increase in efficacy.

Lunar influence on prey availability, diet shifts and niche overlap between Engraulidae larvae in tropical mangrove creeks.

The influence of the lunar cycle on prey availability, diet shifts and overlap between larval Anchovia clupeoides and Cetengraulis edentulus was evaluated in mangrove creeks of the Goiana Estuary. Copepod eggs were highly abundant in the first and last quarter, at the full moon and zoea of Ucides cordatus (Ocypodidae) in the new moon. The Engraulidae larvae fed on microcrustaceans, algae and early planktonic stages of benthic organisms. The relative importance of prey varied according to prey availability in all moon phases. Larval diets were more even in the full and new moons, when the relative importance of calanoid copepods and zoeae of U. cordatus as food items increased (index of relative importance, >80% IRI ). Mangrove creeks were very important feeding grounds for engraulid larvae during spring tides. Larval diets were more diverse in the first and last-quarter moon and included protozoeae of Caridean shrimp, larvae of Anomalocardia brasiliana (Veneridae), Isopoda, Gastropoda, ephippium of Daphnia sp. and nauplii of Cirripedia, Harpacticoidia and cyclopoid Copepoda. The last five items were not found in the creeks, suggesting feeding in the main channel. During neap tides, mangrove creeks were probably also used as refugia. These larvae are opportunistic and feed on highly available prey and both species feed on the same items, leading to high dietary overlap in all moon phases. The lunar cycle, which is related to the spring-neap tidal cycle, was the major driver of quantitative and qualitative changes in feeding of engraulid larvae on a short time scale.

Effects of dredging operations on the demersal fish fauna of a South American tropical-subtropical transition estuary.

Changes in the environment and in the composition of fish assemblages in the Paranaguá Estuary (South Brazil) were assessed by comparisons made before, during and after dredging operations, in the same months and areas studied in the previous year. Interactions between year and month were observed for salinity. During the dredging year fish total density was 2 individuals m(-2) and with a total biomass of 104 g m(-2) (among 31 species captured). For the same period the year before, 0·3 individuals m(-2) and 3 g m(-2) were captured (38 species). The number of species showed significant time v. month interactions, assuming that fish species composition varied for both year and month. Total mean density and biomass showed significant differences for interaction time v. month, and density and biomass in the dredging month September 2001 in the main channel were scientifically different from other months. Interaction times v. area were significant for Cathorops spixii (increased biomass), Aspistor luniscutis (increased density), Menticirrhus americanus (decreased biomass) and Cynoscion leiarchus (decreased density and biomass). This suggests that during the dredging process there is a change in the structure of the demersal fish assemblage. The impact (damage and mortality) induced by dredging on the macrobenthic animals along the dredge path attracted adults of C. spixii that reached densities 10 times greater than in the year before. On the other hand, sciaenid species practically disappeared. To contribute to the conservation of the estuarine fish fauna, and maintain fisheries production of the Paranaguá Estuary and surrounding areas, it is recommended that, dredging should be done from the late rainy season to the early dry season. Decisions must take into account the ecological cycles of socio-economically important fish species and prioritize the safe disposal of dredged spoils.

Changes in the composition of ichthyoplankton assemblage and plastic debris in mangrove creeks relative to moon phases.

Lunar influence on the distribution of fish larvae, zooplankton and plastic debris in mangrove creeks of the Goiana Estuary, Brazil, was studied over a lunar cycle. Cetengraulis edentulus, Anchovia clupeoides and Rhinosardinia bahiensis were the most abundant fish larvae (56·6%), independent of the moon phase. The full moon had a positive influence on the abundance of Gobionellus oceanicus, Cynoscion acoupa and Atherinella brasiliensis, and the new moon on Ulaema lefroyi. The full and new moons also influenced the number of zoeae and megalopae of Ucides cordatus, protozoeae and larvae of caridean shrimps, and the number of hard and soft plastic debris, both <5 and >5 mm. Micro and macroplastics were present in samples from all 12 creeks studied, at densities similar to the third most abundant taxon, R. bahiensis. Cetengraulis edentulus and R. bahiensis showed a strong positive correlation with the last quarter moon, when there was less zooplankton available in the creeks and higher abundance of microplastic threads. Anchovia clupeoides, Diapterus rhombeus, U. lefroyi and hard microplastics were positively associated with different moon phases, when calanoid copepods, Caridean larvae and zoeae of U. cordatus were highly available in the creeks. Cynoscion acoupa, G. oceanicus and A. brasiliensis were strongly associated with the full moon, when protozoeae of caridean shrimps and megalopae of U. cordatus were also highly available, as were hard and soft macroplastics, paint chips (<5 mm) and soft microplastics. The results reinforce the role of mangrove creeks as nursery habitats. The moon phases influenced the distribution of fish larvae species, zooplankton and plastic debris by changing their compositions and abundances in the mangrove creeks of the Goiana Estuary when under the influence of different tidal current regimes.

Distribution patterns of microplastics within the plankton of a tropical estuary.

The Goiana Estuary was studied regarding the seasonal and spatial variations of microplastics (<5mm) and their quantification relative to the zooplankton. The total density (n 100 m(-3)) of microplastics represented half of the total fish larvae density and was comparable to fish eggs density. Soft, hard plastics, threads and paint chips were found in the samples (n=216). Their origins are probably the river basin, the sea and fisheries (including the lobster fleet). In some occasions, the amount of microplastics surpassed that of Ichthyoplankton. The highest amount of microplastics was observed during the late rainy season, when the environment is under influence of the highest river flow, which induces the runoff of plastic fragments to the lower estuary. The density of microplastics in the water column will determine their bioavailability to planktivorous organisms, and then to larger predators, possibly promoting the transfer of microplastic between trophic levels. These findings are important for better informing researchers in future works and as basic information for managerial actions.

Trophic niche and habitat shifts of sympatric Gerreidae.

The diet and mouth growth rates of three Gerreidae species (Eugerres brasilianus, Eucinostomus melanopterus and Diapterus rhombeus) were assessed at different ontogenetic phases (juveniles, sub-adults and adults) in order to detect allometric growth, and whether they are related to habitat and seasonal changes in the Goiana Estuary, north-east Brazil. The importance of each prey for each ontogenetic phase was described using the index of relative importance. The three species showed seasonal ontogenetic shifts in diet and allometric growth of mouth morphology. They also had an exclusively zoobenthic diet, comprising mainly Polychaeta, Copepoda, Ostracoda, Gastropoda and Bivalvia. Mouth development showed a possible influence on diet changes for E. melanopterus. Significant interactions (P < 0·01) were detected among seasons, areas and ontogenetic phases for the most important prey for E. brasilianus and E. melanopterus. Diet overlaps are evidence of intra and interspecific competition among gerreids for specific prey. A conceptual model of the competition and seasonal diet shifts among ontogenetic phases of gerreids is given. The sediment ingested due to the feeding mechanisms of Gerreidae species could also partially explain the ingestion of synthetic items observed for all ontogenetic phases, which indicates one of a myriad effects of human activities (e.g. artisanal fishery) in this estuary.

Real-world outcomes with durvalumab after chemoradiotherapy in patients with unresectable stage III NSCLC: interim analysis of overall survival from PACIFIC-R.

BACKGROUND: Based on the findings of the PACIFIC trial, consolidation durvalumab following platinum-based chemoradiotherapy (CRT) is a global standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC). An earlier analysis from the ongoing PACIFIC-R study (NCT03798535) demonstrated the effectiveness of this regimen in terms of progression-free survival (PFS). Here, we report the first planned overall survival (OS) analysis. PATIENTS AND METHODS: PACIFIC-R is an observational/non-interventional, retrospective study of patients with unresectable, stage III NSCLC who started durvalumab (10 mg/kg intravenously every 2 weeks) within an AstraZeneca-initiated early access program between September 2017 and December 2018. Primary endpoints are OS and investigator-assessed PFS, estimated using the Kaplan-Meier method. RESULTS: By 30 November 2021, the full analysis set included 1154 participants from 10 countries (median follow-up in censored patients: 38.7 months). Median OS was not reached, and the 3-year OS rate was 63.2% (95% confidence interval 60.3% to 65.9%). Three-year OS rates were numerically higher among patients with programmed death-ligand 1 (PD-L1) expression on ≥1% versus <1% of tumor cells (TCs; 67.0% versus 54.4%) and patients who received concurrent CRT (cCRT) versus sequential CRT (sCRT) (64.8% versus 57.9%). CONCLUSIONS: PACIFIC-R data continue to provide evidence for the effectiveness of consolidation durvalumab after CRT in a large, diverse, real-world population. Better outcomes were observed among patients with PD-L1 TCs ≥1% and patients who received cCRT. Nevertheless, encouraging outcomes were still observed among patients with TCs <1% and patients who received sCRT, supporting use of consolidation durvalumab in a broad population of patients with unresectable, stage III NSCLC.

Early development of marine catfishes (Ariidae): from mouth brooding to the release of juveniles in nursery habitats.

The development and allometric growth patterns of the ariid catfishes Cathorops spixii and Cathorops agassizii were studied from neurula embryos to juveniles. The ontogenetic sequence revealed that prior to hatching, embryos of both species are well developed, and their axial and appendicular skeletons are well ossified. Embryos of both species grow slowly longitudinally, but positively allometric growth (growth coefficient, ß1 > 1) was observed in head width and eye diameter. It is hypothesized that these growth patterns might be related to functional priorities for the development of sensory organs, such as the inner ears (otoliths), the Weberian apparatus, eyes and nostrils, during the embryonic period. The first appearance of vertebrae and otoliths, as well as the ossification of otoliths and the Weberian apparatus, occur earlier in embryos of C. agassizii than in embryos of C. spixii. After hatching, mouth-brooded free embryos of both species grow isometrically. Negatively allometric growth was observed in head width and eye diameter during the yolk-sac period, which is expected given that the sensory organs are already formed. Free embryos of C. agassizii are distinguishable from those of C. spixii by their larger eyes, longer snouts, longer heads and heavier yolk sacs. The end of the yolk-sac period is characterized by a direct change from free embryo to juvenile, without a true larval period. The juveniles of the two species can also be distinguished from each other by the larger eyes of C. agassizii compared with C. spixii, as in adult fishes.

Photoinactivation of Aedes aegypti larvae using riboflavin as photosensitizer.

More than half of the global population lives in areas where the Aedes aegypti mosquito is present. Efforts have been made to deal with the population of this mosquito in the larval and adult stages to prevent outbreaks of diseases (Dengue, Zika, Chikungunya, and Yellow Fever). In this scenario, photodynamic inactivation may be an effective alternative method to control this vector population. To evaluate the efficacy of the riboflavin - B2 vitamin - as photosensitizer (PS) in the photodynamic inactivation of Ae. aegypti larvae, different concentrations (0; 0.005; 0.010; 0.025; 0.050; 0.075 and 0.100 mg mL-1) were evaluated under white light from RGB LEDs at a light dose of 495.2  J cm-2. The results reveal that riboflavin can be successfully applied as a PS agent to photoinactivate Ae. aegypti larvae, showing its potential to deal with the larvae population.

Influence of moon phase on fish assemblages in estuarine mangrove tidal creeks.

Significant differences in the composition of fish assemblages during different moon phases were detected in mangrove tidal creeks of the Goiana Estuary. The numbers of Zabaleta anchovy Anchovia clupeoides, Tarpon snook Centropomus pectinatus and Guavina Guavina guavina as well as at least 15 other species showed significant changes according to moon phase and were higher in terms of individuals (32%) and mass (34%) during the new moon.

The fate of plastic litter within estuarine compartments: An overview of current knowledge for the transboundary issue to guide future assessments.

Plastics can enter biogeochemical cycles and thus be found in most ecosystems. Most studies emphasize plastic pollution in oceanic ecosystems even though rivers and estuaries are acknowledged as the main sources of plastics to the oceans. This review detected few studies approaching the transboundary issue, as well as patterns of estuarine gradients in predicting plastic distribution and accumulation in water, sediments, and organisms. Quantities of plastics in estuaries reach up to 45,500 items m-3 in water, 567,000 items m-3 in sediment, and 131 items per individual in the biota. The role of rivers and estuaries in the transport of plastics to the ocean is far from fully understood due to small sample sizes, short-term approaches, sampling techniques that underestimate small plastics, and the use of site-specific sampling rather than covering environmental gradients. Microfibres are the most commonly found plastic type in all environmental matrices but efforts to re-calculate pathways using novel sampling techniques and estimates are incipient. Microplastic availability to estuarine organisms and rising/sinking is determined by polymer characteristics and spatio-temporal fluctuations in physicochemical, biological, and mineralogical factors. Key processes governing plastic contamination along estuarine trophic webs remain unclear, as most studies used "species" as an ecological unit rather than trophic/functional guilds and ontogenetic shifts in feeding behaviour to understand communities and intraspecific relationships, respectively. Efforts to understand contamination at the tissue level and the contribution of biofouling organisms as vectors of contaminants onto plastic surfaces are increasing. In conclusion, rivers and estuaries still require attention with regards to accurate sampling and conclusions. Multivariate analysis and robust models are necessary to predict the fate of micro- and macroplastics in estuarine environments; and the inclusion of the socio-economic aspects in modelling techniques seems to be relevant regarding management approaches.

Photodynamic control of Aedes aegypti larvae with environmentally-friendly tetra-platinated porphyrin.

This work evaluated the photosensitizing activity of isomeric tetra-cationic porphyrins with peripheral [Pt(bpy)Cl]+ to control the larval population of Aedes aegypti by photodynamic action. The photolarvicidal activity of the tetra-platinated porphyrins at meta and para position (3-PtTPyP and 4-PtTPyP) was evaluated under blue (450 nm), green (525 nm), and red (625 nm) light illumination at 55.0 J cm-2. The meta isomer presented an efficient photolarvicidal activity even at a low concentration (1.2 ppm) in the presence of light, while the para counterpart was inactive regardless of the concentration and illumination. The different responses were related to the improved optical features and higher water solubility of 3-PtTPyP compared to 4-PtTPyP. Additionally, the potential environmental toxicity of 3-PtTPyP was tested in a plant model (Allium cepa test), with no toxicity detected for all used concentrations (1.2 to 12 ppm). Hence, this work reveals that 3-PtTPyP has a great potential to be employed to photodynamically control the insect vector population in an environmentally safe way.

Movement patterns of catfishes (Ariidae) in a tropical semi-arid estuary.

From December 2005 to November 2006, 216 samples were taken from the main channel of the Goiana Estuary, representing a total sampled area of 23 ha. Ariidae species were the most abundant in density (1600 individuals ha(-1), 53%) and biomass (18,813 g ha(-1), 63%). Cathorops spixii was the most abundant in density (1340 individuals ha(-1)) and biomass (14,203 g ha(-1)). The variables: number of species, total density and biomass, showed significant interactions between the factors of areas and seasons (P < 0.01). The highest total density (7394 individuals ha(-1)) and biomass (70,292 g ha(-1)) occurred in the middle and upper estuaries, respectively, during the early-rainy season. The density of C. spixii differed significantly between areas and seasons (P < 0.01), while Cathorops agassizii differed significantly only between seasons (P < 0.01). The biomass differed significantly for the species C. spixii, C. agassizii and Sciades herzbergii between seasons, and C. spixii and C. agassizii between areas. Also, the density and biomass of C. spixii and C. agassizii showed interaction between areas and seasons. Only the biomass of S. herzbergii showed interaction between areas and seasons (P < 0.01). This indicates that seasonal variations influenced the distribution of Ariidae species in the different areas of the Goiana Estuary. Moreover, canonical correspondence analysis highlighted a strongly significant correlation (P < 0.01) between the seasonal variations of the environmental gradients (salinity and water temperature) and distribution of catfishes. The management and conservation of estuaries should take into account the life cycle of these species in different estuarine areas and hydrological seasons.

Muscular dystrophy-related quantitative and chemical changes in adenohypophysis GH-cells in golden retrievers.

Duchenne muscular dystrophy (DMD) is a recessive X-linked lethal condition which affects a boy in every 3300 births. It is caused by the absence of dystrophin, a protein occurring especially within the musculoskeletal system and in neurons in specific regions of the central nervous system (CNS). Growth hormone (GH) inhibition is believed to decrease the severity of DMD and could perhaps be used in its treatment. However, the underlying pathological mechanism is not known. The golden retriever muscular dystrophy dog (GRMD) represents an animal model in the study of DMD. In this paper we investigated the morphological aspects of the adenohypophysis as well as the total number and size of GH-granulated cells using design-based stereological methods in a limited number of dystrophic and healthy golden retrievers. GH-cells were larger (32.4%) in dystrophic dogs than in healthy animals (p=0.01) and they occupied a larger portion (62.5%) of the adenohypophysis volume (p=0.01) without changes in either adenohypophysis volume (p=0.893) or total number of GH-granulated cells (p=0.869). With regard to ultrastructure, granulated cells possessed double-layer electron-dense granules which were evenly distributed in the cytosol. Furthermore, these granules in dystrophic animals occupied a larger proportion of GH-granulated cell volume (66.9%; p=0.008) as well as of all GH-cells in the whole pars distalis of adenohypophysis (77.3%; p=0.035), albeit IGF-1 serum concentration was lower in severe cases. This suggests difficulties in the GH secretion that might possibly be associated to dystrophin absence. In contrast to earlier reports, our data suggest that a lower IGF-1 concentration may be more related to a severe, as opposed to a benign, clinical form of muscular dystrophy.

Myocardial myostatin in spontaneously hypertensive rats with heart failure.

BACKGROUND: Myostatin has been shown to regulate skeletal and cardiac muscle growth. However, its status on long-term hypertrophied myocardium has not been addressed. The purpose of this study was to evaluate the expression of myocardial myostatin and its antagonist follistatin in spontaneously hypertensive rats (SHR) with heart failure. METHODS: Eighteen-month-old SHR were evaluated to identify clinical features of heart failure such as tachypnea/labored respiration and weight loss. After heart failure was detected, rats were subjected to echocardiogram and euthanized. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as controls. Myostatin and follistatin protein expression was assessed by Western blotting. Statistical analysis was performed by Student's t test. RESULTS: All SHR (n=8) presented right ventricular hypertrophy and five had lung congestion. SHR had left chambers hypertrophy and dilation (left atrial diameter: WKY 5.73±0.59; SHR 7.28±1.17mm; p=0.004; left ventricular (LV) diastolic diameter/body weight ratio: WKY 19.6±3.1; SHR 27.7±4.7mm/kg; p=0.001), and LV systolic dysfunction (midwall fractional shortening: WKY 34.9±3.31; SHR 24.8±3.20%; p=0.003). Myocyte diameter (WKY 23.1±1.50, SHR 25.5±1.33µm; p=0.004) and myocardial interstitial collagen fraction (WKY 4.86±0.01; SHR 8.36±0.02%; p<0.001) were increased in the SHR. Myostatin (WKY 1.00±0.16; SHR 0.77±0.23 arbitrary units; p=0.035) and follistatin (WKY 1.00±0.35; SHR 0.49±0.18 arbitrary units; p=0.002) expression was lower in SHR. Myostatin and follistatin expression negatively correlated with LV diastolic diameter-to-body weight ratio and LV systolic diameter, and positively correlated with midwall fractional shortening. CONCLUSION: Myostatin and follistatin protein expression is reduced in the long-term hypertrophied myocardium from spontaneously hypertensive rats with heart failure.