Caterpillar nuclei (CN) are characterized by their peculiar morphology, with chromatin distributed in clusters and running along the longitudinal axis of the nucleus. They can be observed in normal ...hearts of fetuses as well as in hearts of children and adults with rheumatic heart disease. This study has demonstrated by means of ploidy studies with digital image analysis that in the fetal heart (20.5+/-1.8 weeks) the CN (diploid = 5.6+/-8.4%; tetraploid = 46.2+/-24.2%; hypertetraploid = 46.9+/-26.3%) present higher DNA content than non-caterpillar myocyte nuclei (diploid = 89.4+/-6.2%; tetraploid = 10.0+/-4.1%; hypertetraploid = 1.5+/-1.3%) (P=0.000001, 0.00013, and 0.000038, respectively). Expression of proliferation cell nuclear antigen (PCNA; 30.6+/-11.7% in CN and 13.4+/-7.3% in non-caterpillar myocyte nuclei; P=0.0115) and cyclin B1 (2.8+/-3.8% and 12.6+/-15.6%, respectively; P=n.s.) was also positive in these nuclei. In conclusion, these results suggest that there exists a relationship between CN morphology and myocyte replication phenomena.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
2.
Syphilitic aortitis. Commentary COHEN, Mauricio G; ANDERSON, R. David; NAVIA, Daniel ...
Catheterization and cardiovascular interventions,
2001, Volume:
52, Issue:
2
Journal Article
Peer reviewed
Full text
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
3.
Syphilitic aortitis Cohen, Mauricio G.; Anderson, R. David; Navia, Daniel ...
Catheterization and cardiovascular interventions,
February 2001, Volume:
52, Issue:
2
Journal Article
From January 1983 to July 1985, 64 patients underwent left ventricular aneurysmectomy in our surgical unit. In 11 (17%) of these cases, the lesion was a variant of the true aneurysm that included an ...extremely thin (1- to 2-mm), well-defined area of myocardium. In 9 of the cases, the aneurysm was confirmed preoperatively by means of high-quality ventriculography (high resolution and many hues of gray). Surgical and pathologic criteria established the lesion's clinical significance. To the best of our knowledge, these aneurysms constitute a heretofore undescribed variant of the classic true left ventricular aneurysm, exhibiting certain gross characteristics of the false left ventricular aneurysm and sharing with false aneurysms their greater risk of rupture. While it is impossible to tell whether these aneurysms are progressing toward rupture, we believe that all such lesions should undergo urgent repair in the presence of cardiac symptoms. Following aneurysmectomy, ventriculoplasty or septoplasty using an elliptical woven Dacron patch helps to preserve the internal contour and surface anatomy of the ventricle. In our series, this procedure resulted in early and late postoperative mortality figures comparable to those associated with the surgical treatment of classic true left ventricular aneurysms.
The aim of this study was to evaluate the effect of microclimatic conditions (temperature and relative humidity) on the reproduction of land snails (Helix aspersa). For this, incubation’s chambers ...were conditioned with different four levels of relative humidity and temperature. Posture, length of incubation and hatching rate were evaluated. It was concluded that 81.0 ± 0.63% of relative humidity and 23.9 ± 0.39 °C of temperature the best results are achieved. DOI: 10.17268/sci.agropecu.2013.04.03
Since the 1980s, chronic kidney disease (CKD) affecting all ages has increased by almost 25%. This increase may be partially attributable to lifestyle changes and increased global consumption of a ...“western” diet, which is typically energy dense, low in fruits and vegetables, and high in animal protein and ultra-processed foods. These modern food trends have led to an increase in the consumption of advanced glycation end products (AGEs) in conjunction with increased metabolic dysfunction, obesity and diabetes, which facilitates production of endogenous AGEs within the body. When in excess, AGEs can be pathological via both receptor-mediated and non-receptor-mediated pathways. The kidney, as a major site for AGE clearance, is particularly vulnerable to AGE-mediated damage and increases in circulating AGEs align with risk of CKD and all-cause mortality. Furthermore, individuals with significant loss of renal function show increased AGE burden, particularly with uraemia, and there is some evidence that AGE lowering via diet or pharmacological inhibition may be beneficial for CKD. This review discusses the pathways that drive AGE formation and regulation within the body. This includes AGE receptor interactions and pathways of AGE-mediated pathology with a focus on the contribution of diet on endogenous AGE production and dietary AGE consumption to these processes. We then analyse the contribution of AGEs to kidney disease, the evidence for dietary AGEs and endogenously produced AGEs in driving pathogenesis in diabetic and non-diabetic kidney disease and the potential for AGE targeted therapies in kidney disease.
Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also ...indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Leber congenital amaurosis (LCA) is an inherited retinal dystrophy that causes childhood blindness. Photoreceptors are especially sensitive to an intronic mutation in the cilia-related gene CEP290, ...which causes missplicing and premature termination, but the basis of this sensitivity is unclear. Here, we generated differentiated photoreceptors in three-dimensional optic cups and retinal pigment epithelium (RPE) from iPSCs with this common CEP290 mutation to investigate disease mechanisms and evaluate candidate therapies. iPSCs differentiated normally into RPE and optic cups, despite abnormal CEP290 splicing and cilia defects. The highest levels of aberrant splicing and cilia defects were observed in optic cups, explaining the retinal-specific manifestation of this CEP290 mutation. Treating optic cups with an antisense morpholino effectively blocked aberrant splicing and restored expression of full-length CEP290, restoring normal cilia-based protein trafficking. These results provide a mechanistic understanding of the retina-specific phenotypes in CEP290 LCA patients and potential strategies for therapeutic intervention.
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•Generation of 3D optic cups with opsin-expressing photoreceptors and outer segments•A CEP290-LCA intronic mutation creates a cryptic exon that impairs ciliogenesis•Aberrant splicing is increased in photoreceptors compared to other cell types•Antisense oligonucleotide can block the cryptic exon and restore CEP290 function
Parfitt et al. derived human 3D optic cup organoids to model LCA, a retinal dystrophy associated with aberrant CEP290 splicing leading to cilia defects. Retinal-specific defects result from higher aberrant CEP290 splicing in photoreceptors versus other cells, and treating cups with an antisense oligonucleotide restored CEP290 protein, function, and ciliation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There is a paucity of data on whether Australian university students are meeting specific nutrient guidelines, and the relationship between diet and physical activity patterns with body composition ...and metabolic health. In this study, biomedical students from The University of Queensland were recruited (150 males and 211 females, 19–25 years), and nutritional intake (ASA24-Australia) and physical activity levels (Active Australia Survey) quantified. Body composition (height, waist circumference, body mass, BMI, and percentage body fat; BOD POD) and metabolic health (oral glucose tolerance test) were also measured. Median daily energy intake was 6760 kJ in females and 10,338 kJ in males, with more than 30% of total energy coming from energy-dense, nutrient-poor foods. Only 1 in 10 students met fruit or vegetable recommendations, with less than one third meeting recommendations for fibre, calcium, and potassium. Intakes of calcium and iron were particularly low among female students, with only 16% and 6% of students meeting the recommended dietary intake (RDI), respectively. The majority of males and almost half of all females exceeded the suggested dietary target (SDT) for sodium. Sufficient physical activity (≥150 min over ≥5 sessions per week) was met by more than 80% of students. Body composition and blood glucose concentrations were largely normal but an early sign of insulin resistance (HOMA-IR > 2.0), measured in a subset of students, was present in 21% of males and 17% of females. Modest reductions in blood glucose levels and percentage body fat were associated with increasing vigorous activity. Low intakes of fibre, calcium, and potassium could be corrected by increasing fruit, vegetable, and dairy intake, and, among females, health promotion messages focusing on iron-rich foods should be prioritised. While these nutrient deficiencies did not translate into immediate metabolic heath concerns, dietary behaviours can track into adulthood and have lasting effects on overall health.
VEGF as a potential target in lung cancer Frezzetti, Daniela; Gallo, Marianna; Maiello, Monica R. ...
Expert opinion on therapeutic targets,
10/2017, Volume:
21, Issue:
10
Journal Article
Peer reviewed
Introduction The vascular endothelial growth factor A (VEGF) is the main mediator of angiogenesis. In addition, VEGF contributes to cancer growth and metastasis directly targeting tumor cells. VEGF ...overexpression and/or high VEGF serum levels have been reported in lung cancer.
Areas covered We searched Pubmed for relevant preclinical studies with the terms 'lung cancer' 'VEGF' and 'in vivo'. We also searched the Clinicaltrials.gov database, the FDA and the EMA websites for the most recent updates on clinical development of anti-VEGF agents.
Expert opinion VEGF plays an important role in sustaining the development and progression of lung cancer and it might represent an attractive target for therapeutic strategies. Nevertheless, clinical trials failed to attend the promising expectations deriving from preclinical studies with anti-VEGF agents. To improve the efficacy of anti-VEGF therapies in lung cancer, potential strategies might be the employment of combinatory therapies with immune checkpoint inhibitors or agents that inhibit signaling pathways and proangiogenic factors activated in response to VEGF blockade, and the identification of novel targets in the VEGF cascade. Finally, the identification of predictive markers might help to select patients who are more likely to respond to anti-angiogenic drugs.
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