Growth and puberty after treatment for acute lymphoblastic leukemia

Over the last 20 years, after combining treatment of chemotherapy and radiotherapy, there has been an improvement in the survival rate of acute lymphoblastic leukemia patients, with a current cure rate of around 70%. Children with the disease have been enrolled into international treatment protocols designed to improve survival and minimize the serious irreversible late effects. Our oncology unit uses the international protocol: GBTLI LLA-85 and 90, with the drugs methotrexate, cytosine, arabinoside, dexamethasone, and radiotherapy. However, these treatments can cause gonadal damage and growth impairment. PATIENTS AND METHOD: The authors analyzed 20 children off therapy in order to determine the role of the various doses of radiotherapy regarding endocrinological alterations. They were divided into 3 groups according to central nervous system prophylaxis: Group A underwent chemotherapy, group B underwent chemotherapy plus radiotherapy (18 Gy), and group C underwent chemotherapy plus radiotherapy (24 Gy). Serum concentrations of LH, FSH, GH, and testosterone were determined. Imaging studies included bone age, pelvic ultrasound and scrotum, and skull magnetic resonance imaging. RESULTS: Nine of the patients who received radiotherapy had decreased pituitary volume. There was a significant difference in the response to GH and loss of predicted final stature (Bayley-Pinneau) between the 2 irradiated groups and the group that was not irradiated, but there was no difference regarding the radiation doses used (18 or 24 Gy). The final predicted height (Bayley-Pinneau) was significantly less (P = 0.0071) in both groups treated with radiotherapy. Two girls had precocious puberty, and 1 boy with delayed puberty presented calcification of the epididymis. CONCLUSION: Radiotherapy was been responsible for late side effects, especially related to growth and puberty.

Aging and Alzheimer's disease: Searching for novel molecular cues

Tese de Doutoramento em Ciências da Saúde

From the periphery to the brain: Lipocalin-2, a friend or foe?

Lipocalin-2 (LCN2) is an acute-phase protein that, by binding to iron-loaded siderophores, acts as a potent bacteriostatic agent in the iron-depletion strategy of the immune system to control pathogens. The recent identification of a mammalian siderophore also suggests a physiological role for LCN2 in iron homeostasis, specifically in iron delivery to cells via a transferrin-independent mechanism. LCN2 participates, as well, in a variety of cellular processes, including cell proliferation, cell differentiation and apoptosis, and has been mostly found up-regulated in various tissues and under inflammatory states, being its expression regulated by several inducers. In the central nervous system less is known about the processes involving LCN2, namely by which cells it is produced/secreted, and its impact on cell proliferation and death, or in neuronal plasticity and behaviour. Importantly, LCN2 recently emerged as a potential clinical biomarker in multiple sclerosis and in ageing-related cognitive decline. Still, there are conflicting views on the role of LCN2 in pathophysiological processes, with some studies pointing to its neurodeleterious effects, while others indicate neuroprotection. Herein, these various perspectives are reviewed and a comprehensive and cohesive view of the general function of LCN2, particularly in the brain, is provided.

Characterization of the oculomotor alterations in inicial phase of Multiple Sclerosis

Dissertação de mestrado em Advanced Optometry

Nanotechnological approaches using curcumin and Withania somnifera: neuroprotection and antimicrobial activities

Tese de Doutoramento em Biologia de Plantas

Development of polymeric nanoparticles containing neuroprotective compounds of Hypericum perforatum

Tese de Doutoramento em Biologia das Plantas - MAP BIOPLANT

HOXA9 as a key regulator in glioma initiation, aggressiveness and response to therapy

Tese de Doutoramento em Ciências da Saúde

The role of IFNγ in higher brain function: in health and under chronic stress

Tese de Doutoramento em Ciências da Saúde

Hydrogels and cell based therapies in spinal cord injury regeneration

Spinal cord injury (SCI) is a central nervous system- (CNS-) related disorder for which there is yet no successful treatment. Within the past several years, cell-based therapies have been explored for SCI repair, including the use of pluripotent human stem cells, and a number of adult-derived stem and mature cells such as mesenchymal stem cells, olfactory ensheathing cells, and Schwann cells. Although promising, cell transplantation is often overturned by the poor cell survival in the treatment of spinal cord injuries. Alternatively, the therapeutic role of different cells has been used in tissue engineering approaches by engrafting cells with biomaterials. The latter have the advantages of physically mimicking the CNS tissue, while promoting a more permissive environment for cell survival, growth, and differentiation. The roles of both cell- and biomaterial-based therapies as single therapeutic approaches for SCI repair will be discussed in this review. Moreover, as the multifactorial inhibitory environment of a SCI suggests that combinatorial approaches would be more effective, the importance of using biomaterials as cell carriers will be herein highlighted, as well as the recent advances and achievements of these promising tools for neural tissue regeneration.

Mesenchymal stem cells secretome as a modulator of the neurogenic niche: Basic insights and therapeutic opportunities

Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) share few characteristics apart from self-renewal and multipotency. In fact, the neurogenic and osteogenic stem cell niches derive from two distinct embryonary structures; while the later originates from the mesoderm, as all the connective tissues do, the first derives from the ectoderm. Therefore, it is highly unlikely that stem cells isolated from one niche could form terminally differentiated cells from the other. Additionally, these two niches are associated to tissues/systems (e.g., bone and central nervous system) that have markedly different needs and display diverse functions within the human body. Nevertheless they do share common features. For instance, the differentiation of both NSCs and MSCs is intimately associated with the bone morphogenetic protein family. Moreover, both NSCs and MSCs secrete a panel of common growth factors, such as nerve growth factor (NGF), glial derived neurotrophic factor (GDNF), and brain derived neurotrophic factor (BDNF), among others. But it is not the features they share but the interaction between them that seem most important, and worth exploring; namely, it has already been shown that there are mutually beneficially effects when these cell types are co-cultured in vitro. In fact the use of MSCs, and their secretome, become a strong candidate to be used as a therapeutic tool for CNS applications, namely by triggering the endogenous proliferation and differentiation of neural progenitors, among other mechanisms. Quite interestingly it was recently revealed that MSCs could be found in the human brain, in the vicinity of capillaries. In the present review we highlight how MSCs and NSCs in the neurogenic niches interact. Furthermore, we propose directions on this field and explore the future therapeutic possibilities that may arise from the combination/interaction of MSCs and NSCs.

Fetal behavior and heart rate in twin pregnancy: a review

Fetal movements and fetal heart rate (FHR) are well-established markers of fetal well-being and maturation of the fetal central nervous system. The purpose of this paper is to review and discuss the available knowledge on fetal movements and heart rate patterns in twin pregnancies. There is some evidence for an association or similarity in fetal movement incidences or FHR patterns between both members of twin pairs. However, the temporal occurrence of these patterns seems to be for the most part asynchronous, especially when stricter criteria are used to define synchrony. The available data suggest that fetal behavior is largely independent of sex combination, fetal position, and presentation. Conversely, chorionicity appears to have some influence on fetal behavior, mainly before 30 weeks of gestation. There is preliminary evidence for the continuity of inter-individual differences in fetal activity and FHR patterns over pregnancy. Comparisons between studies are limited by large methodological differences and absence of uniform concepts and definitions. Future studies with high methodological quality are needed to provide a more comprehensive knowledge of normal fetal behavior in twin pregnancy.

Influence of angiotensin II receptor subtypes of the paraventricular nucleus on the physiological responses induced by angiotensin II injection into the medial septal area

OBJECTIVE: We determined the effects of losartan and PD 123319 (antagonists of the AT1 and AT2 angiotensin receptors, respectively), and [Sar¹, Ala8] ANG II (a relatively peptide antagonist of angiotensin receptors) injected into the paraventricular nucleus (PVN) on water and 3% NaCl intake, and the diuretic, natriuretic, and pressor effects induced by administration of angiotensin II (ANG II) into the medial septal area (MSA) of conscious rats. METHODS: Holtzman rats were used . Animals were anesthetized with tribromoethanol (20 mg) per 100 grams of body weight, ip. A stainless steel guide cannula was implanted into the MSA and PVN. All drugs were injected in 0.5-mul volumes for 10-15 seconds. Seven days after brain surgery, water and 3% NaCl intake, urine and sodium excretion, and arterial blood pressure were measured. RESULTS: Losartan (40 nmol) and [Sar¹, Ala8] ANG II (40 nmol) completely eliminated whereas PD 123319 (40 nmol) partially blocked the increase in water and sodium intake and the increase in arterial blood pressure induced by ANG II (10 nmol) injected into the MSA. The PVN administration of PD 123319 and [Sar¹, Ala8] ANG II blocked whereas losartan attenuated the diuresis and natriuresis induced by MSA administration of ANG II. CONCLUSION: MSA involvement with PVN on water and sodium homeostasis and arterial pressure modulation utilizing ANGII receptors is suggested.

Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

Sôbre a patogenia da Grangrena gasona

Since von Hibler gas grangrene has been considered a local infection with systemic symptoms. When we consider some of the symptoms of gas gangrene, those of the central nervous system are in evidence beeing similar to those observed in tetanus and botulism. It is likely therefore that gas gangrene intoxication and the disease caused by it are of neurotoxic nature. With Almeida Cardoso and Araujo Costa we were able to demonstrate lesions in the central nervous system of animals wich had been intoxicated during a short period of time as well in those with intoxication of longer duration. In acute intoxication, after intracreneal inoculation, severe alterations were seen within 20 to 30 minutes in the cells of the spinal cord, specially in motor cells and also in some cells of the posterior cord and spinal bulb. The changes consisted in chromatolysis and picnosis and were more marked in animals intoxicated with Clostridium histolyticum and Cl. perfringens toxines. Myelin sheet was unchanged. in delayed intoxication with greater and repeated dosis lesions of the central nervous system (brain, protuberance, medula ablongate and medula spinal) were observed. They consisted in hyperemia, perivascular hemorrages in white and grey substances, oedema, accumulation of glia cells with enlarged and hyperchromatic nuclei, fragmentation of the myelin sheet and balooning degeneration of the described by Spielmeyer. Such changes were found in the swollen and hemorragic zones and were generally similar to those found in the acute type of Spielmeyer 9acute swelling and liquefation). Other changes found sometimes were agglutination of Nissl's bodies, sinous appearence of the dendritic endings, shruncken cells of Spielmeyer and neuronophagy around "ghost" cells. In short the changes...

The life history of Hepatozoon leptodactyli (Lesage, 1908) Pessoa, 1970: a parasite of the common laboratory animal: the frog of the genus Leptodactylus

The main object of the present paper is to furnish a brief account to the knowledgement of Protozoa parasitic in common Brazilian frog of the genus Leptodactylus for general students in Zoology and for investigators that use this frog as a laboratory animal. Hepatozoon leptodactyli (Haemogregarina leptodactyli) was found in two species of frogs - Leptodactylus ocellatus and L. pentadactylus - in which develop schizogony whereas sporogony occurs in the leech Haementeria lutzi as was obtainded in experimental conditions. Intracellular forms have been found in peripheral circulation, chiefly in erythrocytes, but we have found them in leukocytes too. Tissue stages were found in frog, liver, lungs, spleen, gut, brain and heart. The occurence of hemogregarine in the Central Nervous System was recorded by Costa & al,(13) and Ball (2). Some cytochemical methods were employed in attempt to differentiate gametocytes from trophozoites in the peripheral blood and to characterize the cystic membrane as well. The speorogonic cycle was developed in only one specie of leech. A brief description of the parasite is given.