The effects of altered neurogenic microRNA levels and their involvement in the aggressiveness of periventricular glioblastoma.

INTRODUCTION: Glioblastoma multiforme is the most common primary brain tumour, with the least favourable prognosis. Despite numerous studies and medical advances, it continues to be lethal, with an average life expectancy of 15 months after chemo-radiotherapy. DEVELOPMENT: Recent research has addressed several factors associated with the diagnosis and prognosis of glioblastoma; one significant factor is tumour localisation, particularly the subventricular zone, which represents one of the most active neurogenic niches of the adult human brain. Glioblastomas in this area are generally more aggressive, resulting in unfavourable prognosis and a shorter life expectancy. Currently, the research into microRNAs (miRNA) has intensified, revealing different expression patterns under physiological and pathophysiological conditions. It has been reported that the expression levels of certain miRNAs, mainly those related to neurogenic processes, are dysregulated in oncogenic events, thus favouring gliomagenesis and greater tumour aggressiveness. This review discusses some of the most important miRNAs involved in subventricular neurogenic processes and their association with glioblastoma aggressiveness. CONCLUSIONS: MiRNA regulation and function play an important role in the development and progression of glioblastoma; understanding the alterations of certain miRNAs involved in both differentiation and neural and glial maturation could help us to better understand the malignant characteristics of glioblastoma.

The effects of altered neurogenic microRNA levels and their involvement in the aggressiveness of periventricular glioblastoma. / Efecto de la alteración de los niveles de expresión de microARN neurogénicos y su implicación en la agresividad de glioblastomas localizados en la región paraventricular.

INTRODUCTION: Glioblastoma multiforme is the most common primary brain tumour, with the least favourable prognosis. Despite numerous studies and medical advances, it continues to be lethal, with an average life expectancy of 15 months after chemo-radiotherapy. DEVELOPMENT: Recent research has addressed several factors associated with the diagnosis and prognosis of glioblastoma; one significant factor is tumour localisation, particularly the subventricular zone, which represents one of the most active neurogenic niches of the adult human brain. Glioblastomas in this area are generally more aggressive, resulting in unfavourable prognosis and a shorter life expectancy. Currently, the research into microRNAs (miRNA) has intensified, revealing different expression patterns under physiological and pathophysiological conditions. It has been reported that the expression levels of certain miRNAs, mainly those related to neurogenic processes, are dysregulated in oncogenic events, thus favouring gliomagenesis and greater tumour aggressiveness. This review discusses some of the most important miRNAs involved in subventricular neurogenic processes and their association with glioblastoma aggressiveness. CONCLUSIONS: MiRNA regulation and function play an important role in the development and progression of glioblastoma; understanding the alterations of certain miRNAs involved in both differentiation and neural and glial maturation could help us to better understand the malignant characteristics of glioblastoma.

Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease. / La eritropoyetina humana recombinante reduce la disfunción sensoriomotora y el deterioro cognitivo en ratas con enfermedad renal crónica.

INTRODUCTION: Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. METHODS: Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. RESULTS: Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. CONCLUSIONS: rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD.

Neuroprotective effects of phytochemicals on dopaminergic neuron cultures. / Efecto neuroprotector de fitoquímicos en cultivo de neuronas dopaminérgicas.

INTRODUCTION: Parkinson's disease is a progressive neurodegenerative disorder characterised by a loss of dopaminergic neurons in the substantia nigra pars compacta, which results in a significant decrease in dopamine levels and consequent functional motor impairment. DEVELOPMENT: Although its aetiology is not fully understood, several pathogenic mechanisms, including oxidative stress, have been proposed. Current therapeutic approaches are based on dopamine replacement drugs; these agents, however, are not able to stop or even slow disease progression. Novel therapeutic approaches aimed at acting on the pathways leading to neuronal dysfunction and death are under investigation. CONCLUSIONS: In recent years, such natural molecules as polyphenols, alkaloids, and saponins have been shown to have a neuroprotective effect due to their antioxidant and anti-inflammatory properties. The aim of our review is to analyse the most relevant studies worldwide addressing the benefits of some phytochemicals used in in vitro models of Parkinson's disease.

Blood biochemistry of olive ridley (Lepidochelys olivacea) sea turtles foraging in northern Sinaloa, Mexico.

Blood parameters provide an excellent tool to evaluate the health status of wildlife. However, there are few studies about health parameters of sea turtles in Mexico. For olive ridley turtles (Lepidochelys olivacea), no information was available to establish the health baseline for the species. The objective of this study was to establish reference blood biochemistry values for olive ridley turtles in the northern Sinaloa foraging area. Between 2013 and 2015, 82 olive ridley turtles were captured. Body condition index (BCI) presented a mean of 1.46 ± 0.14 (1.17-2.02) that categorized the population with excellent body condition; in addition, 99% of the turtles captured had a good physical appearance. Blood was collected for biochemistry analysis from 60 turtles. Significantly higher values of total protein, albumin, A/G ratio (albumin/globulin) and PCV (packed cell volume or hematocrit) were observed in adult when compared to subadult turtles. On the other hand, no significant differences were found when females and males were compared. Based on the BCI, physical assessment, and blood parameters, and compared to other sea turtle species, olive ridley turtles in northern Sinaloa were considered in excellent health. To the best of our knowledge, this is the first study to establish normal blood biochemistry values of foraging olive ridley turtles in northern Sinaloa.

New records of tick-associated spotted fever group Rickettsia in an Amazon-Savannah ecotone, Brazil.

Human rickettsiosis has been recorded in the Amazon Biome. However, the epidemiological cycle of causative rickettsiae has not been fully accounted for in the Amazon region. This study investigates the presence of spotted fever group (SFG) Rickettsia spp. in free-living unfed ticks of the Amblyomma genus. The study was conducted in seven municipalities in Rondonia State, Brazil, where the main biomes are Amazon forest, Brazilian Savannah and their ecotones (areas of ecological tension between open ombrophilous forest and savannah). The following tick species were collected: Amblyomma cajennense (sensu lato) s.l., A. cajennense (sensu stricto) s.s., A. coelebs, A. naponense, A. oblongoguttatum, A. romitii, A. scalpturatum and A. sculptum. A total of 167 adults, 248 nymphs and 1004 larvae were subjected to DNA extraction and polymerase chain reaction (PCR) to determine the presence of SFG Rickettsia spp. PCR-positive samples included: one A. cajennense s.s. female and one A. cajennense s.l. male from a rural area in Vilhena Municipality; 10 nymphs and a sample of larvae of A. cajennense s.l. from a peri-urban area in Cacoal Municipality; and an A. oblongoguttatum adult male from a rural area of Pimenta Bueno Municipality. All sequences obtained exhibited 100% identity with Rickettsia amblyommatis sequences. This is the first confirmation of SFG Rickettsia in an A. oblongoguttatum tick. Furthermore, this is the first record of SFG Rickettsia in the municipalities targeted by this study. These results warn that SFG Rickettsia circulation poses a threat in Rondonia State (among Amazon-Savannah ecotones), and that this threat is increased by the fact that SFG Rickettsia infect a human-biting tick species hitherto unconfirmed as a vector.

Development of the endocrine pancreas and novel strategies for ß-cell mass restoration and diabetes therapy.

Diabetes mellitus represents a serious public health problem owing to its global prevalence in the last decade. The causes of this metabolic disease include dysfunction and/or insufficient number of ß cells. Existing diabetes mellitus treatments do not reverse or control the disease. Therefore, ß-cell mass restoration might be a promising treatment. Several restoration approaches have been developed: inducing the proliferation of remaining insulin-producing cells, de novo islet formation from pancreatic progenitor cells (neogenesis), and converting non-ß cells within the pancreas to ß cells (transdifferentiation) are the most direct, simple, and least invasive ways to increase ß-cell mass. However, their clinical significance is yet to be determined. Hypothetically, ß cells or islet transplantation methods might be curative strategies for diabetes mellitus; however, the scarcity of donors limits the clinical application of these approaches. Thus, alternative cell sources for ß-cell replacement could include embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells. However, most differentiated cells obtained using these techniques are functionally immature and show poor glucose-stimulated insulin secretion compared with native ß cells. Currently, their clinical use is still hampered by ethical issues and the risk of tumor development post transplantation. In this review, we briefly summarize the current knowledge of mouse pancreas organogenesis, morphogenesis, and maturation, including the molecular mechanisms involved. We then discuss two possible approaches of ß-cell mass restoration for diabetes mellitus therapy: ß-cell regeneration and ß-cell replacement. We critically analyze each strategy with respect to the accessibility of the cells, potential risk to patients, and possible clinical outcomes.

Trace elements in blood of sea turtles Lepidochelys olivacea in the Gulf of California, Mexico.

This study determined the concentrations of heavy metals in blood collected from Pacific Ridley sea turtles (Lepidochelys olivacea) inhabiting the coast of Guasave, Mexico, in the Gulf of California. The highest reported metal concentration in blood was Zn, followed by Se. Of nonessential toxic metals, As was reported in higher percentage compared to Cd. The concentrations of metals detected were present as follows: Zn > Se > Mn > As > Ni > Cd > Cu. Cd concentration in blood is higher in our population in comparison with other populations of L. olivacea, and even higher in other species of sea turtles. Our study reinforces the usefulness of blood for the monitoring of the levels of contaminating elements, and is easily accessible and nonlethal for sea turtles.

Selected heavy metals and selenium in the blood of black sea turtle (Chelonia mydas agasiizzi) from Sonora, Mexico.

The concentration of heavy metals (Zn, Cd, Ni, Cu, Mn) and selenium (Se) was analyzed in blood collected from 12 black turtles (Chelonia mydas agasiizzi) captured in Canal del Infiernillo, Punta Chueca, Mexico. The most abundant metals were Zn (63.58 µg g(-1)) and Se (7.66 µg g(-1)), and Cd was the lower (0.99 µg g(-1)). The sequential concentrations of trace metals were Zn > Se > Cu > Mn > Ni > Cd. In conclusion, this information is important as a baseline when using blood as tissue analysis of heavy metals; however, these levels could represent recent exposure in foraging grounds of black turtles in the Sea of Cortez.

Coronaviruses in bats from Mexico.

Bats are reservoirs for a wide range of human pathogens including Nipah, Hendra, rabies, Ebola, Marburg and severe acute respiratory syndrome coronavirus (CoV). The recent implication of a novel beta (ß)-CoV as the cause of fatal respiratory disease in the Middle East emphasizes the importance of surveillance for CoVs that have potential to move from bats into the human population. In a screen of 606 bats from 42 different species in Campeche, Chiapas and Mexico City we identified 13 distinct CoVs. Nine were alpha (α)-CoVs; four were ß-CoVs. Twelve were novel. Analyses of these viruses in the context of their hosts and ecological habitat indicated that host species is a strong selective driver in CoV evolution, even in allopatric populations separated by significant geographical distance; and that a single species/genus of bat can contain multiple CoVs. A ß-CoV with 96.5 % amino acid identity to the ß-CoV associated with human disease in the Middle East was found in a Nyctinomops laticaudatus bat, suggesting that efforts to identify the viral reservoir should include surveillance of the bat families Molossidae/Vespertilionidae, or the closely related Nycteridae/Emballonuridae. While it is important to investigate unknown viral diversity in bats, it is also important to remember that the majority of viruses they carry will not pose any clinical risk, and bats should not be stigmatized ubiquitously as significant threats to public health.

Baseline heavy metals and metalloid values in blood of loggerhead turtles (Caretta caretta) from Baja California Sur, Mexico.

Environmental pollution due to heavy metals is having an increased impact on marine wildlife accentuated by anthropogenic changes in the planet including overfishing, agricultural runoff and marine emerging infectious diseases. Sea turtles are considered sentinels of ecological health in marine ecosystems. The objective of this study was to determine baseline concentrations of zinc, cadmium, copper, nickel, selenium, manganese, mercury and lead in blood of 22 clinically healthy, loggerhead turtles (Caretta caretta), captured for several reasons in Puerto López Mateos, Baja California Sur, Mexico. Zinc was the most prevalent metal in blood (41.89 µg g⁻¹), followed by Selenium (10.92 µg g⁻¹). The mean concentration of toxic metal Cadmium was 6.12 µg g⁻¹ and 1.01µg g⁻¹ respectively. Mean concentrations of metals followed this pattern: Zn>Se>Ni>Cu>Mn>Cd>Pb and Hg. We can conclude that blood is an excellent tissue to measure in relatively non-invasive way baseline values of heavy metals in Caretta caretta.

[Molecular aspects of hepatic encephalopathy]. / Aspectos moleculares de la encefalopatía hepática.

INTRODUCTION: Liver fibrosis and its end stage, cirrhosis, is an enormous worldwide health problem. Hepatic encephalopathy (HE) or portal-systemic encephalopathy continues to be a major clinical problem of long-term cirrhosis. In this review we emphasise the molecular basis of HE and the involvement of oxidative stress in the development of this disease. BACKGROUND: Several studies suggest that the pathogenesis of HE could be multifactorial and have implicated different factors, such as alterations in blood brain barrier, substances; such as ammonia and manganese, neurotransmission disorders such as dopamine, glutamate and GABA. DEVELOPMENT: HE is a severe complication of both acute and chronic liver failure. Neuropathologically, it is characterized by astrocyte changes known as Alzheimer type II astrocytosis. In addition, astrocytes manifest altered expression of astrocyte-specific proteins, such as, glial fibrillary acidic protein, glutamine synthetase, monoamine oxidase and peripheral type benzodiazepine receptors. CONCLUSIONS: HE is a complex neuropsychiatric syndrome associated with liver failure. These alterations are products of increases in oxidative stress in brain due to neurotoxin activity. The main strategy for HE treatment is directed at ammonia reduction, which can be achieved either by decreasing its absorption/production or increasing its removal.

Aspectos moleculares de la encefalopatía hepática / Molecular aspects of hepatic encephalopathy

Introducción: La fibrosis hepática y su etapa final, la cirrosis, representan un enorme problema de salud mundial. La encefalopatía hepática (EH) o encefalopatía portosistémica es una afección clínica de la cirrosis a largo plazo. En esta revisión se destacan las bases moleculares de la EH, así como el papel del estrés oxidativo en el desarrollo de esta enfermedad.Fuentes: Diversos estudios señalan que la EH es de origen multifactorial, las alteraciones en la barrera hematoencefálica, sustancias como el amonio y el manganeso, así como alteraciones en la neurotransmisión de dopamina, glutamato y GABA, se han implicado en la patogenia de esta enfermedad. Desarrollo: La EH es una complicación severa de la insuficiencia hepática tanto aguda como crónica. Neuropatológicamente, se caracteriza por cambios astrocitarios conocidos como astrocitosis Alzheimer tipo II y por la expresión alterada de proteínas específicas de astrocito, como la proteína acídica fibrilar glial, la glutamina sintetasa, los inhibidores de la monoaminooxidasa y los receptores periféricos tipo benzodiacepina.Conclusiones: La EH es un síndrome neuropsiquiátrico complejo asociado a una falla hepática. Estas alteraciones son producto de un incremento de estrés oxidativo en el cerebro como consecuencia de la acción de neurotoxinas. La principal estrategia para el tratamiento de la EH se dirige a la reducción del amonio, ya sea por la disminución de su absorción/producción o promoviendo su eliminación (AU)

Introduction: Liver fibrosis and its end stage, cirrhosis, is an enormous worldwide health problem. Hepatic encephalopathy (HE) or portal-systemic encephalopathy continues to be a major clinical problem of long-term cirrhosis. In this review we emphasise the molecular basis of HE and the involvement of oxidative stress in the development of this disease.Background: Several studies suggest that the pathogenesis of HE could be multifactorial and have implicated different factors, such as alterations in blood brain barrier, substances; such as ammonia and manganese, neurotransmission disorders such as dopamine, glutamate and GABA.Development: HE is a severe complication of both acute and chronic liver failure. Neuropathologically, it is characterized by astrocyte changes known as Alzheimer type II astrocytosis. In addition, astrocytes manifest altered expression of astrocyte-specific proteins, such as, glial fibrillary acidic protein, glutamine synthetase, monoamine oxidase and peripheral type benzodiazepine receptors. Conclusions:HE is a complex neuropsychiatric syndrome associated with liver failure. These alterations are products of increases in oxidative stress in brain due to neurotoxin activity. The main strategy for HE treatment is directed at ammonia reduction, which can be achieved either by decreasing its absorption/production or increasing its removal (AU)

Essential veterinary education in conservation medicine and ecosystem health: a global perspective.

Conservation medicine is an emerging discipline that links human and animal health with ecosystem health and global environmental change. The biosphere is threatened by several pervasive and synergistic phenomena that are the result of increasing human pressures on the planet: climate change, biological impoverishment (loss of biodiversity and ecological processes), emerging infectious diseases ('pathogen pollution') and global 'toxification' (pollutants such as endocrine-disrupting chemicals). These factors are working in concert to diminish human, domestic animal, wildlife and environmental health on this planet. By including conservation medicine and ecosystem health into veterinary curricula worldwide we can train young veterinarians that will help change paradigms and be able to form transdisciplinary teams. These veterinary professionals will develop new tools for assessing and monitoring ecological health and will be prepared to fulfil critical roles in sustaining global ecological health.

Essential veterinary education in zoological and wildlife medicine: a global perspective.

The current veterinary curriculum leaves graduates ill-equipped for careers in the field of zoological and wildlife medicine. Further postgraduate training is required to be an effective zoo or wildlife veterinarian. However, whether or not students choose to specialise in this field at a later date, the veterinary curriculum should cover several issues that are related to wildlife and zoo animals, including conservation biology, zoology, behaviour, physiology and conservation medicine. These subjects are essential, as we are preparing students to work in a world in which there is a global trade in wild animals, an increasing number of emerging infectious diseases and numerous environmental threats (habitat fragmentation, climate change) linked to anthropogenic change. Veterinary students should also be exposed to new opportunities to identify field and laboratory tools for the management and possible treatment of diseases in captive and wild populations and ecosystems using both in situ and ex situ approaches to conservation.

Collaborative research approaches to the role of wildlife in zoonotic disease emergence.

Emerging infectious diseases are a key threat to public health and the majority are caused by zoonotic pathogens. Here we discuss new collaborative approaches to understanding the process of zoonotic disease emergence that link veterinary medicine, public health, and ecological approaches: conservation medicine and one health. We demonstrate how studies on the underlying drivers of disease emergence (bushmeat hunting, wildlife trade, and deforestation) can provide ways to model, predict, and ultimately prevent zoonotic disease emergence and spread.

RT-PCR detection of the expression of the polymerase gene of a novel reptilian herpesvirus in tumor tissues of green turtles with fibropapilloma.

An alpha-herpesvirus has recently been associated with green turtle fibropapilloma (FP). To further understand the etiological role of this newfound green turtle herpesvirus (GTHV) in the pathogenesis of FP, expression of GTHV polymerase ( pol) gene was determined in tumors and normal-appearing nontumor tissues and organs from five green turtles suffering multiple fibropapillomas, using reverse transcription-polymerase chain reaction (RT-PCR). Amplification of RNA prepared from tumor tissues evidenced the substantial expression of GTHV DNA pol gene in all specimens tested (15/15). However, GTHV pol gene expression in normal-appearing tissues and organs of affected animals was limited (4/45), and GTHV mRNA was detected only in periorbital tissue (1/2), gall bladder (2/5) and lung (1/5) by nested RT-PCR. By contrast, RT-PCR evaluation of RNA isolated from non-tumored turtles revealed undetectable expression of this herpesvirus gene. cDNA sequence analysis revealed that GTHV gene sequences were identical in different tumors. Our data represent the first evidence of the replication of this putative turtle herpesvirus in affected green turtles and fibropapilloma tissues are always active sites of GTHV mRNA synthesis. These findings extend and substantiate the pathogenic association of GTHV with FP.

Quantitative analysis of herpesvirus sequences from normal tissue and fibropapillomas of marine turtles with real-time PCR.

Quantitative real-time PCR has been used to measure fibropapilloma-associated turtle herpesvirus (FPTHV) pol DNA loads in fibropapillomas, fibromas, and uninvolved tissues of green, loggerhead, and olive ridley turtles from Hawaii, Florida, Costa Rica, Australia, Mexico, and the West Indies. The viral DNA loads from tumors obtained from terminal animals were relatively homogeneous (range 2-20 copies/cell), whereas DNA copy numbers from biopsied tumors and skin of otherwise healthy turtles displayed a wide variation (range 0.001-170 copies/cell) and may reflect the stage of tumor development. FPTHV DNA loads in tumors were 2.5-4.5 logs higher than in uninvolved skin from the same animal regardless of geographic location, further implying a role for FPTHV in the etiology of fibropapillomatosis. Although FPTHV pol sequences amplified from tumors are highly related to each other, single signature amino acid substitutions distinguish the Australia/Hawaii, Mexico/Costa Rica, and Florida/Caribbean groups.