We have previously demonstrated inverse associations between maternal 25(OH)-vitamin D status and perinatal DNA methylation at the retinoid-X-receptor-alpha (RXRA) locus and between RXRA methylation and offspring bone mass. We therefore... more
We have previously demonstrated inverse associations between maternal 25(OH)-vitamin D status and perinatal DNA methylation at the retinoid-X-receptor-alpha (RXRA) locus and between RXRA methylation and offspring bone mass. We therefore used an existing randomised trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial of 1000IU/day cholecalciferol or matched placebo from 14 weeks' gestation until delivery. Umbilical cord (fetal) tissue was collected at birth and frozen at -80 C (n = 453). Pyrosequencing was used to undertake DNA methylation analysis at 10 CpG sites within the RXRA locus (identified previously). T-tests were used to assess differences between treatment groups in methylation at the three most representative CpG sites. Overall, methylation levels were significa...
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Fucosyltransferase 2 (FUT2) controls the production of digestive and respiratory epithelia of histo-blood group antigens involved in the attachment of pathogens. The aim of our study was to relate FUT2 variants to reported... more
Fucosyltransferase 2 (FUT2) controls the production of digestive and respiratory epithelia of histo-blood group antigens involved in the attachment of pathogens. The aim of our study was to relate FUT2 variants to reported gastrointestinal and respiratory illnesses in infancy. In the Southampton Women's Survey, FUT2 genetic variants (single-nucleotide polymorphisms [SNPs] rs601338 and rs602662) were genotyped in 1831 infants and related to infant illnesses, after adjustment for sex, breastfeeding duration, and potential confounders. For FUT2 SNP rs601338, the risk ratios for ≥1 bout of diarrhea during ages 6-12 months and ages 12-24 months per additional risk (G) allele were 1.23 (95% confidence interval [CI], 1.08-1.4; P = .002) and 1.41 (95% CI, 1.24-1.61; P = 1.7 × 10-7), respectively; the risk ratio for ≥1 diagnosis of a lower respiratory illness (ie, pneumonia or bronchiolitis) during ages 12-24 months per additional G allele was 2.66 (95% CI, 1.64-4.3; P = .00007). Similar...
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In patients with mtDNA maintenance disorders mtDNA deletions sporadically form and clonally expand within individual muscle fibers, causing respiratory chain deficiency. This study aimed to investigate the first visible sign of... more
In patients with mtDNA maintenance disorders mtDNA deletions sporadically form and clonally expand within individual muscle fibers, causing respiratory chain deficiency. This study aimed to investigate the first visible sign of respiratory chain deficiency. Serial skeletal muscle cryosections from patients with multiple mitochondrial DNA deletions were subjected to subcellular immunofluorescent, histochemical and genetic analysis. We report respiratory chain deficient perinuclear foci containing mtDNA deletions, which show local elevations of both mitochondrial mass and mtDNA copy number. These subcellular foci of respiratory chain deficiency are associated with a local increase in mitochondrial biogenesis and unfolded protein response (UPR ) signaling pathways. We also find that the commonly reported pattern of segmental mitochondrial deficiency is consistent with the three-dimensional organization of the mitochondrial network. We propose that mtDNA deletions first exceed the bioch...
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Several studies suggest that low birthweight resulting from restricted intrauterine growth can leave a metabolic footprint which may persist into adulthood. To investigate this, we performed metabolomic profiling on 5036 female twins,... more
Several studies suggest that low birthweight resulting from restricted intrauterine growth can leave a metabolic footprint which may persist into adulthood. To investigate this, we performed metabolomic profiling on 5036 female twins, aged 18-80, with weight at birth information available from the TwinsUK cohort and performed independent replication in two additional cohorts. Out of 422 compounds tested, 25 metabolites associated with birthweight in these twins, replicated in 1951 men and women from the Hertfordshire Cohort Study (HCS, aged 66) and in 2391 men and women from the North Finland Birth 1986 cohort (NFBC, aged 16). We found distinct heterogeneity between sexes and, after adjusting for multiple tests and heterogeneity, two metabolites were reproducible overall (propionylcarnitine and 3-4-hydroxyphenyllactate). Testing women only, we found other metabolites associated with lower birthweight from the meta-analysis of the three cohorts (2-hydroxy-butyric acid and γ-glutamyll...
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All proposed definitions of sarcopenia include the measurement of muscle mass, but the techniques and threshold values used vary. Indeed, the literature does not establish consensus on the best technique for measuring lean body mass.... more
All proposed definitions of sarcopenia include the measurement of muscle mass, but the techniques and threshold values used vary. Indeed, the literature does not establish consensus on the best technique for measuring lean body mass. Thus, the objective measurement of sarcopenia is hampered by limitations intrinsic to assessment tools. The aim of this study was to review the methods to assess muscle mass and to reach consensus on the development of a reference standard. Literature reviews were performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis working group on frailty and sarcopenia. Face-to-face meetings were organized for the whole group to make amendments and discuss further recommendations. A wide range of techniques can be used to assess muscle mass. Cost, availability, and ease of use can determine whether the techniques are better suited to clinical practice or are more useful for research. No one technique subser...
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A loss of muscle mass occurs as a consequence of a range of chronic and acute diseases as well as in older age. This wasting results from an imbalance of protein synthesis and degradation with a reduction in synthesis and resistance to... more
A loss of muscle mass occurs as a consequence of a range of chronic and acute diseases as well as in older age. This wasting results from an imbalance of protein synthesis and degradation with a reduction in synthesis and resistance to anabolic stimulation often reported features. Ribosomes are required for protein synthesis, so changes in the control of ribosome synthesis are potential contributors to muscle wasting. MicroRNAs (miRNAs) are known regulators of muscle phenotype and have been shown to modulate components of the protein synthetic pathway. One miRNA that is predicted to target a number of components of protein synthetic pathway is miR-424-5p, which is elevated in the quadriceps of patients with chronic obstructive pulmonary disease (COPD). Targets of miR-424-5p were identified by Argonaute2 pull down, and the effects of the miRNA on RNA and protein expression were determined by quantitative polymerase chain reaction and western blotting in muscle cells in vitro. Protein...
Research Interests: Internal Medicine (General Medicine), MicroRNA, General Internal Medicine, Medicine, Protein synthesis, and 13 moreCOPD, Resistance, Ribosome, Skeletal Muscle, Chronic Heart Failure, Science Technology, Wasting, Chronic obstructive pulmonary disease, Amino Acid Profile, Geriatrics and Gerontology, Protein Biosynthesis, Life Sciences & Biomedicine, and Muscle wasting
To assess whether different trajectories of weight gain since birth influence bone mineral content (BMC) and areal bone mineral density (aBMD) at 7 years of age. We studied a subsample of 1889 children from the Generation XXI birth cohort... more
To assess whether different trajectories of weight gain since birth influence bone mineral content (BMC) and areal bone mineral density (aBMD) at 7 years of age. We studied a subsample of 1889 children from the Generation XXI birth cohort who underwent whole-body dual-energy radiograph absorptiometry. Weight trajectories identified through normal mixture modeling for model-based clustering and labeled "normal weight gain," "weight gain during infancy," "weight gain during childhood," and "persistent weight gain" were used. Differences in subtotal BMC, aBMD, and size-corrected BMC (scBMC) at age 7 years according to weight trajectories were estimated through analysis of covariance. Compared with the "normal weight gain" trajectory, children in the remaining trajectories had significantly greater BMC, aBMD, and scBMC at age 7 years, with the strongest associations for "persistent weight gain" (girls [BMC: 674.0 vs 559.8 g, aB...
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Osteoporosis is a common disease diagnosed primarily by measurement of bone mineral density (BMD). We undertook a genome-wide association study (GWAS) in 142,487 individuals from the UK Biobank to identify loci associated with BMD as... more
Osteoporosis is a common disease diagnosed primarily by measurement of bone mineral density (BMD). We undertook a genome-wide association study (GWAS) in 142,487 individuals from the UK Biobank to identify loci associated with BMD as estimated by quantitative ultrasound of the heel. We identified 307 conditionally independent single-nucleotide polymorphisms (SNPs) that attained genome-wide significance at 203 loci, explaining approximately 12% of the phenotypic variance. These included 153 previously unreported loci, and several rare variants with large effect sizes. To investigate the underlying mechanisms, we undertook (1) bioinformatic, functional genomic annotation and human osteoblast expression studies; (2) gene-function prediction; (3) skeletal phenotyping of 120 knockout mice with deletions of genes adjacent to lead independent SNPs; and (4) analysis of gene expression in mouse osteoblasts, osteocytes and osteoclasts. The results implicate GPC6 as a novel determinant of BMD,...
Research Interests: Genetics, Developmental Biology, Biology, Medicine, Biological Sciences, and 15 moreHumans, Genome Wide Association Studies, Femur, Female, Animals, Male, Bone Density, Heritability, Glypicans, Calcaneus, GWAS, Genetics Research, Gene expression profiling, LD Score Regression, and Medical and Health Sciences
Musculoskeletal ageing is a major public health concern owing to demographic shifts in the population. Sarcopenia, generally defined as the age-related loss of muscle mass and function, is associated with considerable risk of falls, loss... more
Musculoskeletal ageing is a major public health concern owing to demographic shifts in the population. Sarcopenia, generally defined as the age-related loss of muscle mass and function, is associated with considerable risk of falls, loss of independence in older adults and hospitalization with poorer health outcomes. This condition is therefore associated with increased morbidity and health care costs. As with bone mass, muscle mass and strength increase during late adolescence and early adulthood, but begin to decline substantially from ∼50 years of age. Sarcopenia is characterized by many features, which include loss of muscle mass, altered muscle composition, infiltration with fat and fibrous tissue and alterations in innervation. A better understanding of these factors might help us to develop strategies that target these effects. To date, however, methodological challenges and controversies regarding how best to define the condition, in addition to uncertainty about what outcom...
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Poor intrauterine and childhood growth has been linked with the risk of osteoporosis in later life, a relationship that may in part be mediated through altered epigenetic regulation of genes. We previously identified a region within the... more
Poor intrauterine and childhood growth has been linked with the risk of osteoporosis in later life, a relationship that may in part be mediated through altered epigenetic regulation of genes. We previously identified a region within the promoter of the long non-coding RNA ANRIL encoded by the CDKN2A locus, at which differential DNA methylation at birth showed correlations with offspring adiposity. Given the common lineage of adipocytes and osteoblasts, we investigated the relationship between perinatal CDKN2A methylation and bone mass at ages 4 and 6 years. Using sodium bisulfite pyrosequencing, we measured the methylation status of the 9 CpGs within this region in umbilical cord samples from discovery (n = 332) and replication (n = 337) cohorts of children from the Southampton Women's Survey, whose bone mass was assessed by dual-energy X-ray absorptiomietry (DXA; Hologic Discovery). Inverse associations were found between perinatal CDKN2A methylation and whole-body minus head b...
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Single nucleotide polymorphisms (SNP) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol... more
Single nucleotide polymorphisms (SNP) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. To determine whether SNPs in DHCR7, CYP2R1, CYP24A1 and GC are associated with the response to gestational cholecalciferol supplementation. Within-randomization-group analysis of the MAVIDOS trial of antenatal cholecalciferol supplementation. Hospital antenatal clinics. 682 women of White ethnicity (351 placebo, 331 cholecalciferol) were included. SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1) and rs2282679 (GC) were genotyped. 1000 IU/day cholecalciferol from 14 weeks gestation until delivery. 25(OH)D at randomisation and 34 weeks gestation were measured in a single batch (Diasorin Liaison). Associations between 25(OH)D and the SNPs were assessed by linear regression using an additive model (beta represents t...
Research Interests: Endocrinology, Biology, Vitamin D, Vitamins, Treatment Outcome, and 15 moreMedicine, Linear models, Multivariate Analysis, Pregnancy, Humans, Internal Medicine, Female, Dietary Supplements, Clinical Sciences, Vitamin, Genotype, Adult, Vitamin D Deficiency, alleles, and Paediatrics and reproductive medicine
Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures. A growing body of literature has provided indirect and some direct evidence for possible... more
Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures. A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects. Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have reviewed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases, providing recommendations and guidelines for future studies in this field. Robust mechanistic evidence is available from in vitro studies and in vivo animal studies, usually employing cholecalciferol, calcidiol or calcitriol in pharmacologic rather than physiologic doses. Although many cross-sectional and prospective association studies in humans have shown that low 25-hydroxyvitamin D levels (i.e., <50 nmol/L) are consistently associated with chronic dis...
Research Interests: Multiple sclerosis, Clinical Trial, Diabetes, Cancer, Vitamin D, and 12 moreMortality, Medicine, Humans, Systemic Lupus Erythematosus, Autoimmune diseases, Endocrine, Dietary Supplements, Clinical Sciences, Cardiovascular Diseases, Type 2 Diabetes Mellitus, Vitamin D Deficiency, and Paediatrics and reproductive medicine
Experimental studies show a substantial contribution of early life environment to obesity risk through epigenetic processes. We examined inter-individual DNA methylation differences in human birth tissues associated with child's... more
Experimental studies show a substantial contribution of early life environment to obesity risk through epigenetic processes. We examined inter-individual DNA methylation differences in human birth tissues associated with child's adiposity. We identified a novel association between the level of CpG methylation at birth within the promoter of the long non-coding RNA ANRIL (encoded at CDKN2A) and childhood adiposity at age 6-years. An association between ANRIL methylation and adiposity was also observed in three additional populations; in birth tissues from ethnically diverse neonates, in peripheral blood from adolescents, and in adipose tissue from adults. Additionally, CpG methylation was associated with ANRIL expression in vivo, and CpG mutagenesis in vitro inhibited ANRIL promoter activity. Furthermore, CpG methylation enhanced binding to an Estrogen Response Element within the ANRIL promoter. Our findings demonstrate that perinatal methylation at loci relevant to gene function...
Research Interests: Genetic Epidemiology, Obesity, Biomarkers, Biology, Epigenetics, and 15 moreAdolescent, Medicine, Humans, Child, Methylation, Female, Male, DNA methylation, CpG islands, Young Adult, Infant, Aged, Middle Aged, Adult, and Adiposity
Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the... more
Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the "Task Force") recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although ...
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Current approaches to antenatal vitamin D supplementation do not account for interindividual differences in 25-hydroxyvitamin D (25(OH)D) response. We assessed which maternal and environmental characteristics were associated with 25(OH)D... more
Current approaches to antenatal vitamin D supplementation do not account for interindividual differences in 25-hydroxyvitamin D (25(OH)D) response. We assessed which maternal and environmental characteristics were associated with 25(OH)D after supplementation with cholecalciferol. Within-randomization-group analysis of participants in the Maternal Vitamin D Osteoporosis Study trial of vitamin D supplementation in pregnancy. Hospital antenatal clinics. A total of 829 pregnant women (422 placebo, 407 cholecalciferol). At 14 and 34 weeks of gestation, maternal anthropometry, health, and lifestyle were assessed and 25(OH)D measured. Compliance was determined using pill counts at 19 and 34 weeks. 1000 IU/d of cholecalciferol or matched placebo from 14 weeks of gestation until delivery. 25(OH)D at 34 weeks, measured in a single batch (Diasorin Liaison). 25(OH)D at 34 weeks of gestation was higher in the women randomized to vitamin D (mean [SD], 67.7 [21.3] nmol/L) compared with placebo (4...
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Loss of bone and muscle with advancing age represent a huge threat to loss of independence in later life. "Osteoporosis represents a major public health problem through its association with fragility fractures, primarily of the hip,... more
Loss of bone and muscle with advancing age represent a huge threat to loss of independence in later life. "Osteoporosis represents a major public health problem through its association with fragility fractures, primarily of the hip, spine and distal forearm" (Moselhy et al., 2012). Sarcopenia, the age related loss of muscle mass and function, may add to fracture risk by increasing falls risk. In the context of muscle aging, it is important to remember that it is not just a decline in muscle mass which contributes to the deterioration of muscle function. Other factors underpinning muscle quality come into play, including muscle composition, aerobic capacity and metabolism, fatty infiltration, insulin resistance, fibrosis and neural activation. Genetic, developmental, endocrine and lifestyle factors, such as physical activity, smoking and poor diet have dual effects on both muscle and bone mass in later life and these will be reviewed here. These include poor nutrition, lack...
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Several studies have shown relationships between growth in early life and adult bone mass; in this article, we evaluate the relative contributions of pre- and postnatal factors to bone mass in the seventh decade. A total of 498 eight men... more
Several studies have shown relationships between growth in early life and adult bone mass; in this article, we evaluate the relative contributions of pre- and postnatal factors to bone mass in the seventh decade. A total of 498 eight men and 468 women who were born in Hertfordshire during the period 1931-1939 and still living there were recruited. Detailed birth records were available. Participants attended a clinic where they completed a detailed health questionnaire, before performance of anthropometric measurements and bone densitometry of the proximal femur and lumbar spine (Hologic QDR 4500). Birth weight was associated with bone mineral content in both men (proximal femur: r=0.16, p=0.0003; lumbar spine: r=0.10, p=0.03) and women (proximal femur: r=0.16, p=0.0008; lumbar spine: r=0.11, p=0.03); relationships with bone mineral density were weaker and were significant at the proximal femur in men only (p=0.03). Relationships between weight at 1 y and bone mineral content were ev...
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Research Interests: Genetics, Epidemiology, Biology, Adolescent, Signal Transduction, and 15 moreBiological Sciences, Humans, Child, Blood Glucose, Fasting, Diabetes mellitus, Homeostasis, Adult, Quantitative Trait Loci, Reproducibility of Results, Cell Proliferation, Glucose Homeostasis, Fasting Insulin, Gene Expression Regulation, and Medical and Health Sciences
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To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth... more
To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 × 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 × 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height, their effects on infant head circumference were largely independent of height (P = 3.8 × 10(-7) for rs7980687 and P = 1.3 × 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 × 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume,…
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Research Interests: Hematology, Oncology, Breast Cancer, Medicine, Humans, and 14 moreInternal Medicine, Female, Risk factors, Bisphosphonate derivatives, Bone Loss, Risk Factors, Imidazoles, Aromatase Inhibitor, Antineoplastic Agents, Zoledronic acid, Randomized Controlled Trials as Topic, aromatase, Fracture Risk, and Breast Neoplasms
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Subjects with type 1 diabetes mellitus (T1DM) have decreased bone mineral density and an up to sixfold increase in fracture risk. Yet bone fragility is not commonly regarded as another unique complication of diabetes. Both animals with... more
Subjects with type 1 diabetes mellitus (T1DM) have decreased bone mineral density and an up to sixfold increase in fracture risk. Yet bone fragility is not commonly regarded as another unique complication of diabetes. Both animals with experimentally induced insulin deficiency syndromes and patients with T1DM have impaired osteoblastic bone formation, with or without increased bone resorption. Insulin/IGF1 deficiency appears to be a major pathogenetic mechanism involved, along with glucose toxicity, marrow adiposity, inflammation, adipokine and other metabolic alterations that may all play a role on altering bone turnover. In turn, increasing physical activity in children with diabetes as well as good glycaemic control appears to provide some improvement of bone parameters, although robust clinical studies are still lacking. In this context, the role of osteoporosis drugs remains unknown.
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The technological development of pharmaceutical products based on plant extracts is currently responsible for a large number of recent innovations in healthcare. The objective of this study was to develop and investigate the effect and... more
The technological development of pharmaceutical products based on plant extracts is currently responsible for a large number of recent innovations in healthcare. The objective of this study was to develop and investigate the effect and potential applicability of an ointment-based Bathysa cuspidata extract (BCE) for the management of skin wounds in rats. Three skin wounds of 12 mm in diameter were made on the backs of the animals, which were randomized into 4 groups according to the application received, i.e. the SAL group: 0.9% saline solution, the LAN group: lanolin, the BCE 2.5% group: 2.5% BCE emulsified in lanolin and the BCE 5% group: 5% BCE emulsified in lanolin. The applications were made daily over 21 days, and every 7 days tissue from different wounds was removed. On days 7, 14 and 21, the BCE 2.5% and BCE 5% groups showed the best results in relation to wound closure, and a higher proportion (in length, density and volume) of blood vessels and fibroblasts compared to the other groups. On days 7 and 14, there was a significant increase in the number of mast cells in these 2 groups when compared to the SAL and LAN groups. On day 21, they also had a higher proportion of collagen I than collagen III. B. cuspidata in an ointment base was effective in stimulating tissue cellularity, mast cell recruitment, neoangiogenesis, synthesis and maturation of collagen, epidermal thickness and surface area in scar tissue. These events were potentially related to the best quality and speed for skin regeneration in the rats treated with the BCE ointment. © 2014 S. Karger AG, Basel.
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Environmental factors can influence the reproductive rates in bats, and since morphometric information of bats testis is scarce, we aimed to compare the organization and quantification of the intertubular components in the testes of the... more
Environmental factors can influence the reproductive rates in bats, and since morphometric information of bats testis is scarce, we aimed to compare the organization and quantification of the intertubular components in the testes of the bat Molossus molossus, collected in different seasons. Testicular histological sections were evaluated using light and electron microscopy. The intertubular compartment occupied an average 10% of the testes, being predominately constituted of Leydig cells (LC). The percentages of the testes occupied by the intertubular compartment and by LC were significantly higher in summer, while the other intertubular components did not vary significantly among the seasons. As suspected under light microscopy, the ultrastructural analysis confirmed the existence of multinucleated LC during winter. The increase in the nuclear percentage of LC in winter seems to have caused the decrease of the cytoplasmatic measurements in that season, as well as in the volume of LC. The highest cytoplasmatic values and volume of LC registered in the spring, summer, and fall can be related to greater activity of this cell in these seasons. The higher investment in intertubular tissue and in LC observed in summer, compared to winter; suggest an increase in the steroidogenic capacity of this bat during summer. The analyses correlating testicular morphometry and abiotic environmental factors in this study confirm the influence of climatic factors on the reproduction of M. molossus.
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Frequent exposure to cadmium (Cd) in low doses is common; however, the long-lasting effects of this exposure are still poorly understood. Therefore in this study we have evaluated long-lasting hepatic morphofunctional adaptations in rats... more
Frequent exposure to cadmium (Cd) in low doses is common; however, the long-lasting effects of this exposure are still poorly understood. Therefore in this study we have evaluated long-lasting hepatic morphofunctional adaptations in rats exposed to low and moderate doses of Cd. Five experimental groups were tested: control (0.9% saline) and other four receiving single intraperitoneal doses of 0.67, 0.74, 0.86 and 1.1 mg of Cd/kg. The animals were killed after eight weeks and the following parameters were analysed: biometrics, oedema, Cd bio-accumulation, collagen, glycogen, lipid droplets, superoxide dismutase (SOD) and catalase (CAT), serum transaminases, liver histopathology and stereology. In all groups exposed to Cd there was significant increase in SOD and CAT activities, ALP levels, proportion of binucleated hepatocytes, nuclei/cytoplasm ratio, macrophages (Kupffer cells) and collagen fibres. In these groups, glycogen accumulation by hepatocytes and the proportion of sinusoidal capillaries were significantly reduced compared with controls. The liver somatic index was increased, and liver oedema was evident in animals exposed to higher dose of Cd. Areas of necrosis were found in animals exposed to the three highest doses. These results indicate that Cd is an extremely toxic bioactive heavy metal, which even at low doses is able to disrupt liver homeostasis. At low and moderate doses, Cd exposure induces morphofunctional pathological remodelling of the hepatic stroma and parenchyma, which remain active after eight weeks. In response to injury, the liver tissue triggers a reactive process by enhancing activation of antioxidant enzymes and collagenogenesis.
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This study investigated the effect of the bark extract of Bathysa cuspidata on paraquat (PQ)-induced extra-pulmonary acute lung injury (ALI) and mortality in rats. ALI was induced with a single dose of PQ (30 mg/kg, i.p.), and animals... more
This study investigated the effect of the bark extract of Bathysa cuspidata on paraquat (PQ)-induced extra-pulmonary acute lung injury (ALI) and mortality in rats. ALI was induced with a single dose of PQ (30 mg/kg, i.p.), and animals were treated with B. cuspidata extract (200 and 400 mg/kg). Analyses were conducted of survival, cell migration, lung oedema, malondialdehyde, proteins carbonyls, catalase, superoxide dismutase, histopathology and the stereology of lung tissue. Rats exposed to PQ and treated with 200 and 400 mg of the extract presented lower mortality (20% and 30%), compared with PQ alone group (50%). Furthermore, lung oedema, septal thickening, alveolar collapse, haemorrhage, cell migration, malondialdehyde and proteins carbonyl levels decreased, and catalase and superoxide dismutase activity were maintained. These results show that the bark extract of B. cuspidata reduced PQ-induced extra-pulmonary ALI and mortality in rats and suggest that these effects may be assoc...