Rosa Imbesi

Treatment with rapamycin ameliorates clinical and histological signs of protracted relapsing experimental allergic encephalomyelitis in Dark Agouti rats and induces expansion of peripheral CD4+CD25+Foxp3+ regulatory T cells

We have presently evaluated the effects of the immunomodulatory drug rapamycin on the course of protracted relapsing experimental allergic encephalomyelitis (PR-EAE) in Dark Agouti (DA) rats, which serves as a preclinical model of multiple sclerosis. The data show that the oral administration of rapamycin at 3 mg/kg for 28 consecutive days significantly ameliorated the course of PR-EAE in DA rats. The rats that received the medication had significantly lower clinical cumulative scores and shorter duration of the disease than did the control rats treated with the vehicle. The milder course of the disease was associated with a reduction of the histopathological signs associated to EAE: increased percentage of splenic CD4+CD25 + Foxp3+ Tregs and concomitant reduction of splenic CD8+T cells. These data suggest that rapamycin has pharmacological potential worthy of consideration in the treatment of MS patients.

Increased levels of interleukin-12 in Plasmodium falciparum malaria: correlation with the severity of disease

Interleukin (IL)‐12, produced by mononuclear phagocytes, activates the T‐helper 1 (Th1) cells and helps, as a mediator, the innate immune response to intracellular microbes. In Plasmodium falciparum infection, this proinflammatory cytokine has immunoregulatory functions with effects on the immune response to the blood stage of disease, but also induces protection and reduces malarial anaemia. In this study, the levels of IL‐12 were determined in 73 African children, aged 2–144 months (median 19·5 months), who had severe or mild P. falciparum malaria. IL‐12 was determined using the enzyme‐linked immunosorbent assay. The levels of IL‐12 were found to be significantly elevated (21·6 ± 18·3 pg/ml) in patients who suffered less severely from the disease. In contrast, the levels of IL‐12 were found to be lower (13·1 ± 7·11 pg/ml) in patients who suffered more severely from the disease.

Effects of dietary extra-virgin olive oil on oxidative stress resulting from exhaustive exercise in rat skeletal muscle: a morphological study.

Physical exercise induces oxidative stress through production of reactive oxygen species and can cause damage to muscle tissue. Oxidative stress, resulting from exhaustive exercise is high and improvement of antioxidant defenses of the body may ameliorate damage caused by free radicals. Extra-virgin olive oil is widely considered to possess anti-oxidative properties. The aim of this study was to determine if extra-virgin olive oil improved the adaptive responses in conditions of oxidative stress. Twenty-four 12-week-old male Sprague-Dawley rats were divided in three groups: (1) rats fed with standard chow and not subjected to physical exercise; (2) rats fed with standard chow and subjected to exhaustive exercise; (3) rats fed with a diet rich in oleic acid, the major component of extra-virgin olive oil, and subjected to exhaustive exercise. Exhaustive exercise consisted of forced running in a five-lane 10° inclined treadmill at a speed of 30 m/min for 70-75 min. We studied some biomarkers of oxidative stress and of antioxidant defenses, histology and ultrastructure of the Quadriceps femoris muscle (Rectus femoris). We observed that, in rats of group 3, parameters indicating oxidative stress such as hydroperoxides and thiobarbituric acid-reactive substances decreased, parameters indicating antioxidant defenses of the body such as non-enzymatic antioxidant capacity and Hsp70 expression increased, and R. femoris muscle did not show histological and ultrastructural alterations. Results of this study support the view that extra-virgin olive oil can improve the adaptive response of the body in conditions of oxidative stress.

Physical activity ameliorates cartilage degeneration in a rat model of aging: A study on lubricin expression

Osteoarthritis (OA) is a common musculoskeletal disorder characterized by slow progression and joint tissue degeneration. Aging is one of the most prominent risk factors for the development and progression of OA. OA is not, however, an inevitable consequence of aging and age‐related changes in the joint can be distinguished from those that are the result of joint injury or inflammatory disease. The question that remains is whether OA can be prevented by undertaking regular physical activity. Would moderate physical activity in the elderly cartilage (and lubricin expression) comparable to a sedentary healthy adult? In this study we used physical exercise in healthy young, adult, and aged rats to evaluate the expression of lubricin as a novel biomarker of chondrocyte senescence. Immunohistochemistry and western blotting were used to evaluate the expression of lubricin in articular cartilage, while enzyme‐linked immunosorbent assay was used to quantify lubricin in synovial fluid. Morphological evaluation was done by histology to monitor possible tissue alterations. Our data suggest that moderate physical activity and normal mechanical joint loading in elderly rats improve tribology and lubricative properties of articular cartilage, promoting lubricin synthesis and its elevation in synovial fluid, thus preventing cartilage degradation compared with unexercised adult rats.

PROLACTIN INCREASES HO-1 EXPRESSION AND INDUCES VEGF PRODUCTION IN HUMAN MACROPHAGES

The pituitary hormone prolactin (PRL) is a multifunctional polypeptide which exerts a role on cell proliferation and may also contribute to cell differentiation. PRL is also produced by immune cells and is regarded as a key component of the neuroendocrine–immune loop and as a local regulator of macrophage response. The involvement of PRL in regulating monocyte/macrophage functions is suggested by the presence of PRL receptors in these cells. It has been shown that PRL possess both angiogenic and antiangiogenic effects. Recently, we revealed that augmentation of HO‐1 activity enhances PRL‐mediated angiogenesis in human endothelial cells. Since macrophages are key participants in angiogenesis our objective was to investigate the effect of PRL also in human macrophages. In vitro treatment of macrophages with PRL was found to increase both heme oxygenase‐1 (HO‐1) expression and protein synthesis in a time and dose dependent manner as quantified respectively by reverse‐transcriptase real‐time polymerase chain reaction and Western blot analysis. PRL‐treated macrophages also showed an enhanced release of vascular endothelial growth factor (VEGF) as demonstrated by ELISA assay. Furthermore, to determine whether PRL‐induced HO‐1 activity was required for VEGF production by macrophages, the effect of PRL on the induction of VEGF was studied in the presence of an inducer stannic chloride (SnCl2) and of an inhibitor stannic mesoporphyrin (SnMP) of HO activity. Our observations suggest that PRL may regulate monocyte activation and influences not only immune function but also angiogenesis.

Pregnancy, embryo-fetal development and nutrition: physiology around fetal programming

Abstract The purpose of this brief narrative review is to highlight the role of nutrition during the gestation period. We focused on the possible effects of imbalance of some nutrients in normal course of pregnancy and embryonic

Ameliorative effect of PACAP and VIP against increased permeability in a model of outer blood retinal barrier dysfunction.

Breakdown of outer blood retinal barrier (BRB) due to the disruption of tight junctions (TJs) is one of the main factors accounting for diabetic macular edema (DME), a major complication of diabetic retinopathy. Previously it has been shown that PACAP and VIP are protective against several types of retinal injuries. However, their involvement in the maintenance of outer BRB function during DME remains uncovered. Here, using an in vitro model of DME, we explored the effects of both PACAP and VIP. Human retinal pigment epithelial cells (ARPE19) were cultured for 26 days either in normal glucose (5.5 mM, NG) or in high glucose (25 mM, HG). In addition, to mimic the inflammatory aspect of the diabetic milieu, cells were also treated with IL-1β (NG+IL-1β and HG+IL-1β). Effects of PACAP or VIP on cells permeability were evaluated by measuring both apical-to-basolateral movements of fluorescein isothyocyanate (FITC) dextran and transepithelial electrical resistance (TEER). Expression of TJ-related proteins was evaluated by immunoblot. Results demonstrated that NG+IL-1β and, to a greater extent, HG+IL-1β significantly increased FITC-dextran diffusion, paralleled by decreased TEER. PACAP or VIP reversed both of these effects. Furthermore, HG+IL-1β-induced reduction of claudin-1 and ZO-1 expression was reversed by PACAP and VIP. Occludin expression was not affected in any of the conditions tested. Altogether, these finding show that both peptides counteract HG+IL-1β-induced damage in ARPE19 cells, suggesting that they might be relevant to the maintenance of outer BRB function in DME.

Somitogenesis: From somite to skeletal muscle

Myogenesis is controlled by an elaborate system of extrinsic and intrinsic regulatory mechanisms in all development stages. The aim of this review is to provide an overview of the different stages of myogenesis and muscle differentiation in mammals, starting from somitogenesis and analysis of the different portions that constitute the mature somite. Particular attention was paid to regulatory genes, in addition to mesodermal stem cells, which represent the earliest elements of myogenesis. Finally, the crucial role of growth factors, molecules of vital importance in contractile regulation, hormones and their function in skeletal muscle differentiation, growth and metabolism, and the role played by central nervous system, are discussed.

Effects of high-tryptophan diet on pre- and postnatal development in rats: a morphological study

PurposeTryptophan is an essential amino acid, precursor of serotonin. Serotonin (5HT) regulates the secretion of pituitary growth hormone (GH), which in turn stimulates the liver to produce insulin-like growth factor-I (IGF-I) that is necessary for development and growth. The aim of our study was to investigate the effects of an excess of tryptophan in the diet of pregnant rats on the differentiation of skeletal muscle tissue.MethodsWe conducted an immunohistochemical study on the IGF-I expression in hepatic and muscle tissues in offspring, and then, we associated this molecular data with morphological effects on the structure of the muscle fibers and hepatic tissue at different postnatal weeks, from birth to sexual maturity. Measurements of 5HT, GH in blood, and of tryptophan hydroxylase (Tph) activity in gastrointestinal tracts tissue were also taken.ResultsHyperserotonemia and higher values of Tph activity were detected in both pregnant rats and pups. Very low levels of GH were detected in experimental pups. Morphological alterations of the muscle fibers and lower IGF-I expression in hepatic and muscle tissue in pups were found.ConclusionsOur data suggest that an excess of tryptophan in the diet causes hyperserotonemia in fetus. Hyperserotonemia results in an excess of serotonin in the brain where it has an adverse effect on the development of serotonergic neurons. The affected neurons do not regulate optimally the secretion of pituitary GH that consequently decreases. This limits stimulation in the liver to produce IGF-I, crucial for development and growth of pups.

Advantages of exercise in rehabilitation, treatment and prevention of altered morphological features in knee osteoarthritis. A narrative review.

Knee osteoarthritis (OA) represents one of the most common causes of disability in the world. It leads to social, psychological and economic costs with financial consequences, also because a further increase is expected. Different knee OA treatments are usually considered in relation to the stage of the disease, such as surgical management and pharmacologic and non-pharmacologic treatments. Treatment should begin with the safest and least invasive one, before proceeding to more invasive, expensive ones. Non-pharmacologic, behavioral treatments of knee OA are recommended not only in rehabilitation but also in prevention because many risk factors, such as excess weight, obesity and joint tissue inflammation, can be monitored and thus prevented. In the present review, we analyze data from the most recent literature in relation to the effects of physical exercise on prevention, therapy and rehabilitation in knee OA. All data suggest that physical exercise is an effective, economical and accessible tool to everyone, in the treatment and prevention of knee OA. The literature search was conducted on PubMed, Scopus and Google Scholar using appropriate keywords in relation to knee osteoarthritis.