Role of Pv-aCO2 gradient and Pv-aCO2/Ca-vO2 ratio during cardiac surgery: a retrospective observational study.

INTRODUCTION: Arterial lactate, mixed venous O2 saturation, venous minus arterial CO2 partial pressure (Pv-aCO2) and the ratio between this gradient and the arterial minus venous oxygen content (Pv-aCO2/Ca-vO2) were proposed as markers of tissue hypoperfusion and oxygenation. The main goals were to characterize the determinants of Pv-aCO2 and Pv-aCO2/Ca-vO2, and the interchangeability of the variables calculated from mixed and central venous samples. METHODS: 35 cardiac surgery patients were included. Variables were measured or calculated: after anesthesia induction (T1), end of surgery (T2), and at 6...8.ßhours intervals after ICU admission (T3 and T4). RESULTS: Macrohemodynamics was characterized by increased cardiac index and low systemic vascular resistances after surgery (p.ß<.ß0.05). Hemoglobin, arterial-pH, lactate, and systemic O2 metabolism showed significant changes during the study (p.ß<.ß0.05). Pv-aCO2 remained high and without changes, Pv-aCO2/Ca-vO2 was also high and decreased at T4 (p.ß<.ß0.05). A significant correlation was observed globally and at each time interval, between Pv-aCO2 or Pv-aCO2/Ca-vO2 with factors that may affect the CO2 hemoglobin dissociation. A multilevel linear regression model with Pv-aCO2 and Pv-aCO2/Ca-vO2 as outcome variables showed a significant association for Pv-aCO2 with SvO2, and BE (p.ß<.ß0.05), while Pv-aCO2/Ca-vO2 was significantly associated with Hb, SvO2, and BE (p.ß<.ß0.05) but not with cardiac output. Measurements and calculations from mixed and central venous blood were not interchangeable. CONCLUSIONS: Pv-aCO2 and Pv-aCO2/Ca-vO2 could be influenced by different factors that affect the CO2 dissociation curve, these variables should be considered with caution in cardiac surgery patients. Finally, central venous and mixed values were not interchangeable.

Role of Pv-aCO2 gradient and Pv-aCO2/Ca-vO2 ratio during cardiac surgery: a retrospective observational study

Abstract Introduction: Arterial lactate, mixed venous O2 saturation, venous minus arterial CO2 partial pressure (Pv-aCO2) and the ratio between this gradient and the arterial minus venous oxygen content (Pv-aCO2/Ca-vO2) were proposed as markers of tissue hypoperfusion and oxygenation. The main goals were to characterize the determinants of Pv-aCO2 and Pv-aCO2/Ca-vO2, and the interchangeability of the variables calculated from mixed and central venous samples. Methods: 35 cardiac surgery patients were included. Variables were measured or calculated: after anesthesia induction (T1), end of surgery (T2), and at 6-8 hours intervals after ICU admission (T3 and T4). Results: Macrohemodynamics was characterized by increased cardiac index and low systemic vascular resistances after surgery (p < 0.05). Hemoglobin, arterial-pH, lactate, and systemic O2 metabolism showed significant changes during the study (p < 0.05). Pv-aCO2 remained high and without changes, Pv-aCO2/Ca-vO2 was also high and decreased at T4 (p < 0.05). A significant correlation was observed globally and at each time interval, between Pv-aCO2 or Pv-aCO2/Ca-vO2 with factors that may affect the CO2 hemoglobin dissociation. A multilevel linear regression model with Pv-aCO2 and Pv-aCO2/Ca-vO2 as outcome variables showed a significant association for Pv-aCO2 with SvO2, and BE (p < 0.05), while Pv-aCO2/Ca-vO2 was significantly associated with Hb, SvO2, and BE (p < 0.05) but not with cardiac output. Measurements and calculations from mixed and central venous blood were not interchangeable. Conclusions: Pv-aCO2 and Pv-aCO2/Ca-vO2 could be influenced by different factors that affect the CO2 dissociation curve, these variables should be considered with caution in cardiac surgery patients. Finally, central venous and mixed values were not interchangeable.

Taenia hydatigena larvae vesicular concentrate reduces the egg shedding of Haemonchus contortus associated with the overexpression of abomasal cytokines in lambs.

The expression patterns of some cytokines were compared by RT-qPCR between lambs with and without Taenia hydatigena larvae vesicular concentrate (ThLVC) administration and subsequent infection with Haemonchus contortus. Lambs that received ThLVC prior to infection with H. contortus showed lower (p < 0.03) cumulative FEC (AUC = 18450 ± 3384) than infected lambs who did not receive ThLVC (AUC = 31081 ± 3277). Lambs infected with H. contortus, in general, overexpressed Th1 and Th2 cytokines in abomasal mucosa and abomasal lymph nodes, which seems to indicate a generalized and nonpolarized activation of the immune response by H. contortus. The main immunomodulatory effects of ThLVC were observed in the abomasal fundic region. The lambs that were given ThLVC prior to infection strongly overexpressed most of the studied cytokines representing the Th1 (IFNγ and IL2) and Th2 profiles (IL4, IL5, IL6 and IL10), proinflammatory cytokines (SOD1 and PRDX6) and IgE receptor; in contrast, lambs that were infected but did not receive ThLVC only moderately overexpressed IFNγ, IL4 and IL6. The absence of the significant overexpression of cytokines in lambs that only received ThLVC suggests that this derived from T. hydatigena does not have a stimulating effect per se; however, the presence of H. contortus did produce the highest expression (p < 0.01) cytokine profile among lambs that received ThLVC prior to infection compared to those who did not receive it, so its effect seems to be immunomodulatory and not only immunostimulatory.

Investigating the remediation potential of iron oxide nanoparticles in Cu-polluted soil-plant systems: coupled geochemical, geophysical and biological approaches.

Although the use of iron oxide nanoparticles (IONPs) has high potential in remediation and agriculture, a major hindrance to their use includes the risk of contamination of soil and water resources with underexplored effects of IONPs on biota. The fate, phytotoxicity and remediation potential of IONPs are investigated with soil column experiments using 7 nm-sized magnetite (Fe3O4) nanoparticles (magnNPs) and sunflower (Helianthus annuus). Control soil, magnNP-containing soil (10 g magnNPs per kg soil), copper-polluted soil (500 mg Cu per kg soil) and copper-polluted soil containing magnNPs (10 g magnNPs per kg soil and 500 mg Cu per kg soil) support sunflower growth for 57 and 95 days. In magnNP-exposed plants, the occurrence of magnNPs does not affect the growth of the vegetative aerial parts and photosynthetic efficiency. Decreased lipid peroxidation indicates an enhanced antioxidant enzymatic response of magnNP-exposed plants. In plants grown in Cu- and magnNP-Cu-soils, the physiological and biochemical impacts of excess copper are clearly identified, resulting in growth retardation, decreased pigment contents and photosynthetic efficiency, and increased lipid peroxidation and peroxidase (POD) activities. Based on magnetic susceptibility, a higher amount of magnNPs is detected after 57 days in the roots of magnNP-exposed plants (1400 mg kg-1) than in the roots of magnNP-Cu-exposed plants (920 mg kg-1). In the latter, magnNP internalization is likely hampered because of the plants' physiological responses to Cu toxicity. At the working Cu and magnNP concentrations, magnNPs neither decrease Cu accumulation in the plant tissues nor alleviate the overall growth retardation of sunflowers and certain phytotoxic effects induced by excess Cu. However, this study highlights several positive environmental aspects relative to magnNP use, including the harmless effects of magnNPs on sunflowers (1% magnNPs in soil) and the ability of magnNPs to influence Cu mobility in the soil (which could be even more pronounced at lower Cu concentration).

In vivo and in vitro apoptosis induced by new acaricidal ethyl-carbamates in Rhipicephalus microplus.

The ability of ethyl-4-bromophenylcarbamate (LQM 919) and ethyl-4-chlorophenylcarbamate (LQM 996) to induce in vivo apoptosis of Rhipicephalus microplus ovarian cells and in vitro apoptosis of tick and mammalian cell culture was evaluated. The ovaries of engorged females treated with 1 mg mL-1 LQM 919 or LQM 996 presented more (p < 0.001) peroxidase-TUNEL-positive labeled cells (apoptotic cells) in situ than their respective control groups, and this increase was time-dependent (p < 0.001). The majority of apoptotic cells were observed in the epithelium and ovarian pedicel. HepG2, Vero and Rm-sus cells, as well as cells from primary cultures of R. microplus salivary glands, intestine and ovaries were exposed to different concentrations of the ethyl-carbamates. Both ethyl-carbamates induced a concentration-dependent reduction in the viability of all cell types (p < 0.001). Exposure to the ethyl-carbamates increased caspase 3 activity (p < 0.01) in primary cultures and cell lines, except in HepG2 cells. Fluorescent TUNEL-positive cells were observed in all cell types treated with 600 µM LQM 919 or LQM 996. These results indicate that both ethyl-carbamates induce apoptosis of the ovarian, intestinal and salivary glands cells in R. microplus and strongly suggest that this is their main mechanism of acaricidal action.

DELLA family duplication events lead to different selective constraints in angiosperms.

Gibberellic acid (GA) is a major plant hormone involved in several biological processes from the flowering to the symbiosis with microorganisms. Thus, the GA regulation is crucial for plant biology. This regulation occurs via the DELLA proteins that belong to the GRAS transcription factor family. DELLA proteins are characterised by a DELLA N-terminal and a GRAS C-terminal domains. It is well known that DELLA activity appears after the bryophytes divergence and then evolved in the vascular plant lineages. Here we present the phylogeny of DELLA across 75 species belonging to various lineages from algae, liverworts and angiosperms. Our study confirmed two main duplication events, the first occurring before the angiosperms divergence and the other specific to the eudicots lineage. Comparative analysis of DELLA subclades in angiosperms revealed the loss in Poaceae and strong alteration in other species of the DELLA functional domain in the DELLA2 clade. In addition, molecular evolution analysis suggests that each of the clades (named DELLA1.1, DELLA1.2 and DELLA2) evolved differently but copies of each subclade are under strong purifying selection. This also suggests that, although the DELLA functional domain is altered in DELLA2, DELLA2 orthologs are still functional and operate in a different way compared to DELLA1 copies. In angiosperms, additional duplication events occurred and led to duplicate copies in species, genus or family such as in the Fabaceae subfamily Papilionoideae. This duplication led to the formation of additional paralogs in the DELLA1.2 subclade (DELLA1.2.1 and DELLA1.2.2). Interestingly, both copies appeared to be under relaxing selection revealing different evolutionary fate of the DELLA duplicated copies.

Progesterone in vitro increases growth, motility and progesterone receptor expression in third stage larvae of Toxocara canis.

The in vitro effect of progesterone in T. canis larvae on their enlargement and motility were evaluated, together to the possible presence of progesterone receptors (PRs). T. canis larvae were cultured in RPMI-1640 with different concentrations of progesterone (0, 20, 40, 80, 400 and 800 ng/mL). Enlargement and increases in motility were dependent on the concentration only from 0 to 80 ng/mL (p < 0.05). The mean percentage of PR + cells in newly obtained larvae as measured by flow cytometry was 8.16 ± 0.4. The number of PR + cells increased depending on concentration from 0 to 80 ng/mL (p < 0.001). Cells obtained from larvae stimulated at any of the studied hormone concentrations showed greater mean fluorescence intensity when compared to non-stimulated cells. Additionally, the expression and location of PR + cells were determined in the larvae. The sequence of an amplicon (420-bp) obtained by PCR from T. canis larvae showed 100% homology with a gene fragment that codes for the PR of the dog. PR + cells were immunolocated using confocal microscopy in the intestinal region of the larvae that had been recently obtained. The results of this study show that T. canis larvae can recognize and respond to the presence of progesterone through a molecule possibly able to bind it. Since we previously observed a similar response to prolactin, we suggest that both hormones could participate sequentially in the reactivation of T. canis larvae in pregnant bitches.

Early goal-directed therapy using a physiological holistic view: the ANDROMEDA-SHOCK-a randomized controlled trial.

BACKGROUND: Septic shock is a highly lethal condition. Early recognition of tissue hypoperfusion and its reversion are key factors for limiting progression to multiple organ dysfunction and death. Lactate-targeted resuscitation is the gold-standard under current guidelines, although it has several pitfalls including that non-hypoxic sources of lactate might predominate in an unknown proportion of patients. Peripheral perfusion-targeted resuscitation might provide a real-time response to increases in flow that could lead to a more timely decision to stop resuscitation, thus avoiding fluid overload and the risks of over-resuscitation. This article reports the rationale, study design and analysis plan of the ANDROMEDA-SHOCK Study. METHODS: ANDROMEDA-SHOCK is a randomized controlled trial which aims to determine if a peripheral perfusion-targeted resuscitation is associated with lower 28-day mortality compared to a lactate-targeted resuscitation in patients with septic shock with less than 4 h of diagnosis. Both groups will be treated with the same sequential approach during the 8-hour study period pursuing normalization of capillary refill time versus normalization or a decrease of more than 20% of lactate every 2 h. The common protocol starts with fluid responsiveness assessment and fluid loading in responders, followed by a vasopressor and an inodilator test if necessary. The primary outcome is 28-day mortality, and the secondary outcomes are: free days of mechanical ventilation, renal replacement therapy and vasopressor support during the first 28 days after randomization; multiple organ dysfunction during the first 72 h after randomization; intensive care unit and hospital lengths of stay; and all-cause mortality at 90-day. A sample size of 422 patients was calculated to detect a 15% absolute reduction in mortality in the peripheral perfusion group with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. CONCLUSIONS: If peripheral perfusion-targeted resuscitation improves 28-day mortality, this could lead to simplified algorithms, assessing almost in real-time the reperfusion process, and pursuing more physiologically sound objectives. At the end, it might prevent the risk of over-resuscitation and lead to a better utilization of intensive care unit resources. Trial registration ClinicalTrials.gov Identifier: NCT03078712 (registered retrospectively March 13th, 2017).

RNA sequencing and analysis of three Lupinus nodulomes provide new insights into specific host-symbiont relationships with compatible and incompatible Bradyrhizobium strains.

Nitrogen fixation in the legume root-nodule symbiosis has a critical importance in natural and agricultural ecosystems and depends on the proper choice of the symbiotic partners. However, the genetic determinism of symbiotic specificity remains unclear. To study this process, we inoculated three Lupinus species (L. albus, L. luteus, L. mariae-josephae), belonging to the under-investigated tribe of Genistoids, with two Bradyrhizobium strains (B. japonicum, B. valentinum) presenting contrasted degrees of symbiotic specificity depending on the host. We produced the first transcriptomes (RNA-Seq) from lupine nodules in a context of symbiotic specificity. For each lupine species, we compared gene expression between functional and non-functional interactions and determined differentially expressed (DE) genes. This revealed that L. luteus and L. mariae-josephae (nodulated by only one of the Bradyrhizobium strains) specific nodulomes were richest in DE genes than L. albus (nodulation with both microsymbionts, but non-functional with B. valentinum) and share a higher number of these genes between them than with L. albus. In addition, a functional analysis of DE genes highlighted the central role of the genetic pathways controlling infection and nodule organogenesis, hormones, secondary, carbon and nitrogen metabolisms, as well as the implication of plant defence in response to compatible or incompatible Bradyrhizobium strains.

Progesterone inhibits the in vitro L3/L4 molting process in Haemonchus contortus.

We evaluated the direct effects of progesterone on the morphology, maturation and behavior of Haemonchus contortus larvae in vitro. The presence and location of possible progesterone receptors in these larvae were also determined. The addition of 8ng/mL of progesterone to larval cultures over 10days reduced larval enlargement, while the addition of 160ng/mL of the hormone increased the enlargement. Up to 62% and 65% of the H. contortus larvae molted from third-stage larvae (L3) to fourth-stage larvae (L4) when cultured in RPMI-1640 media without hormone for 5 and 10days, respectively. The addition of different progesterone concentrations (1, 8, 16, 80 and 160ng/mL) to the larval cultures significantly inhibited the molting process within the same periods. The addition of 8ng/mL or higher progesterone concentrations to the cultures significantly increased larval motility (p<0.05) compared with unstimulated larvae. Flow cytometry showed the expression of progesterone receptors (P4-R) in 15% of the cells from newly isolated H. contortus larvae. When the larvae were cultured for 5days in the presence of the hormone, the percentage of P4-R+ cells remained the same. In contrast, unstimulated larvae showed a significant reduction in the number of P4-R+ cells. Using confocal microscopy, a greater concentration of P4-Rs was immunolocated in the anterior portion of the alimentary tract of the larvae, suggesting that the cells in this region are targeted by the hormone. The results of the present study show that H. contortus larvae have possible P4-Rs and respond to this hormone by inhibiting their molting process, thereby suggesting the participation of progesterone in the larval arrest phenomenon.

Experimental transmission of Toxocara canis from Blattella germanica and Periplaneta americana cockroaches to a paratenic host.

The present study assessed the capacity of Blattella germanica and Periplaneta americana to disseminate and transmit infective phases of T. canis to rats, which were used as a model paratenic host. P. americana and B. germanica inoculated orally with T. canis larvated eggs shed eggs and larvae in their fecal matter during the first 6days post-inoculation. Larvae were recovered from the brain, lungs, kidneys and liver of rats that had been inoculated with either infected cockroaches or their feces. ELISAs of serum detected an increase of antibodies anti-T. canis excretion-secretion antigens, whereas Western Blot (WB) showed 4 bands (120, 50, 35 and 28kDa) that were similar to those found in positive control rats. Macroscopically, the liver and kidneys of infected rats had hemorrhagic areas with milk-spot-like lesions. The lungs showed diffuse grey protuberances. Histologically, hemorrhagic areas with leucocytic infiltrate were observed in the liver, lungs and kidneys. Some larvae were found within a granuloma that was surrounded by eosinophils and other leucocytic infiltrates. Larvae were found in the brain, but without inflammatory infiltrate. Both cockroach species that ingested larvated eggs of T. canis may shed viable larvae or eggs in their fecal matter. The induction of specific serum antibodies, presence of larvae in tissues and characteristic lesions associated with larval migration in the organs of rats that had ingested either whole adults or feces of B. germanica or P. americana demonstrate the capacity of these cockroaches to transmit toxocariosis to paratenic hosts.

Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis.

BACKGROUND: Mildly elevated lactate levels (i.e., 1-2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. METHODS: This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. RESULTS: In 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80-1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1-5.7, P = 0.027). CONCLUSIONS: In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010.

Organizational Issues, Structure, and Processes of Care in 257 ICUs in Latin America: A Study From the Latin America Intensive Care Network.

OBJECTIVE: Latin America bears an important burden of critical care disease, yet the information about it is scarce. Our objective was to describe structure, organization, processes of care, and research activities in Latin-American ICUs. DESIGN: Web-based survey submitted to ICU directors. SETTINGS: ICUs located in nine Latin-American countries. SUBJECTS: Individual ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-seven of 498 (52%) of submitted surveys responded: 51% from Brazil, 17% Chile, 13% Argentina, 6% Ecuador, 5% Uruguay, 3% Colombia, and 5% between Mexico, Peru, and Paraguay. Seventy-nine percent of participating hospitals had less than 500 beds; most were public (59%) and academic (66%). ICUs were mainly medical-surgical (75%); number of beds was evenly distributed in the entire cohort; 77% had 24/7 intensivists; 46% had a physician-to-patient ratio between 1:4 and 7; and 69% had a nurse-to-patient ratio of 1 ≥ 2.1. The 24/7 presence of other specialists was deficient. Protocols in use averaged 9 ± 3. Brazil (vs the rest) had larger hospitals and ICUs and more quality, surveillance, and prevention committees, but fewer 24/7 intensivists and poorer nurse-to-patient ratio. Although standard monitoring, laboratory, and imaging practices were almost universal, more complex measurements and treatments and portable equipment were scarce after standard working hours, and in public hospitals. Mortality was 17.8%, without differences between countries. CONCLUSIONS: This multinational study shows major concerns in the delivery of critical care across Latin America, particularly in human resources. Technology was suboptimal, especially in public hospitals. A 24/7 availability of supporting specialists and of key procedures was inadequate. Mortality was high in comparison to high-income countries.

The evolutionary fate of the chloroplast and nuclear rps16 genes as revealed through the sequencing and comparative analyses of four novel legume chloroplast genomes from Lupinus.

The Fabaceae family is considered as a model system for understanding chloroplast genome evolution due to the presence of extensive structural rearrangements, gene losses and localized hypermutable regions. Here, we provide sequences of four chloroplast genomes from the Lupinus genus, belonging to the underinvestigated Genistoid clade. Notably, we found in Lupinus species the functional loss of the essential rps16 gene, which was most likely replaced by the nuclear rps16 gene that encodes chloroplast and mitochondrion targeted RPS16 proteins. To study the evolutionary fate of the rps16 gene, we explored all available plant chloroplast, mitochondrial and nuclear genomes. Whereas no plant mitochondrial genomes carry an rps16 gene, many plants still have a functional nuclear and chloroplast rps16 gene. Ka/Ks ratios revealed that both chloroplast and nuclear rps16 copies were under purifying selection. However, due to the dual targeting of the nuclear rps16 gene product and the absence of a mitochondrial copy, the chloroplast gene may be lost. We also performed comparative analyses of lupine plastomes (SNPs, indels and repeat elements), identified the most variable regions and examined their phylogenetic utility. The markers identified here will help to reveal the evolutionary history of lupines, Genistoids and closely related clades.

La Enfermedad de Parkinson: Etiología, Tratamientos y Factores Preventivos / Parkinson Disease: Etiology, Treatments and Preventive Factors

La enfermedad de Parkinson (EP) es la patología neurodegenerativa motora con mayor incidencia a nivel mundial, cuyas causas aún no son claras. Actualmente no existe cura, pero es posible contar con diferentes tratamientos que permiten aliviar algunos de sus síntomas y enlentecer su curso. Debido a la gran cantidad de informaciones, en ocasiones contradictorias sobre los llamados "factores de riesgo" (entendidos éstos como situaciones que pueden exacerbar la posibilidad de aparición de la enfermedad, incluyendo desde la predisposición familiar hasta la exposición prolongada a substancias exógenas), en esta revisión se pretende ofrecer una panorámica actual sobre factores asociados a la aparición de EP Se revisan también algunos tratamientos que buscan contrarrestar la pérdida de la función dopaminérgica de la substancia nigra (SN) y algunas de las aproximaciones terapéuticas tanto farmacológicas, como por estimulación cerebral profunda (ECP) o por implante celular. Se revisan también investigaciones sobre el potencial terapéutico de compuestos con alta especificidad a receptores colinérgicos (nAChRs) y antagonistas de receptores de adenosina, específicamente del subtipo A2A. Posiblemente durante las próximas décadas, nuestro conocimiento en epigenética pueda arrojar nuevas luces sobre esta interacción, así como sobre las relaciones entre ciertas líneas de microbios intestinales y aparición de EP. En este momento, la alternativa terapéutica que ofrece mayor eficacia es la ECP, sin embargo, a futuro se espera que el desarrollo de nuevas estrategias de implante cerebral pueda ofrecer una cura real de la EP.

Parkinson's disease (PD) is the most prevalent neurodegenerative motor pathology worldwide, the causes of which are still unclear. Currently there is no cure, but it is possible to have different treatments that allow to alleviate some of its symptoms and slow its course. Due to the large amount of information, sometimes contradictory, about the so-called "risk factors" (understood as situations that may exacerbate the possibility of the onset of the disease, from family predisposition to prolonged exposure to exogenous substances), in this review aims to provide a current overview of factors associated with the occurrence of PD. We also review some treatments that seek to counteract the loss of the dopaminergic function of the substance nigra (SN) and some of the therapeutic approaches both pharmacologically, by deep brain stimulation (DBS) or by cellular implantation. Also reviewed investigations on the therapeutic potential of compounds with high specificity to cholinergic receptors (nAChRs) and adenosine receptor antagonists, specifically the A2A subtype. Possibly, during the next decades, our knowledge in epigenetics may shed new light on this interaction, as well as on the relationships between certain lines of intestinal microbes and onset of PD. At this time, the most effective therapeutic alternative is DBS; however, in the future it is expected that the development of new brain implant strategies may offer a real cure for PD.

The in vitro effect of prolactin on the growth, motility and expression of prolactin receptors in larvae of Toxocara canis.

The in vitro effect of prolactin (PRL) on the growth and motility of Toxocara canis larvae was assessed. Additionally, the expression and location of prolactin receptors (PRL-Rs) were determined in the larvae. Larvae of T. canis were incubated with different concentrations of PRL for different periods of time. The stimulated larvae accelerated their enlargement and increased their motility. The mean percentage of PRL-R+ cells in non-stimulated larvae, measured by flow cytometry was 7.3±0.3%. Compared with non-stimulated larvae, the mean fluorescence intensity (p<0.05) increased in larvae incubated with 40ng/mL of PRL for 10 days. A 465-bp length fragment was amplified from larvae gDNA by PCR. The sequence of this fragment showed 99% similarity with the gene fragment that codes for the PRL-R of the domestic dog. A high concentration of PRL-Rs was immune-located in the posterior region of the larval intestine; therefore, the intestinal cells in this region were most likely the targets for this hormone. Based on these results, PRL-Rs were identified in T. canis larvae, and the in vitro stimulation with PRL increased the number of these receptors, accelerated the growth and modified the activity of larvae. All of the above suggest that T. canis larvae are evolutionarily adapted to recognize the PRL of their definitive host and furthermore might explain the reactivation of tissue-arrested larvae during the gestation of bitches, which does not occur in gestating females of other species.

Microcirculatory changes during cardiac surgery with cardiopulmonary bypass. / Alteraciones microcirculatorias en cirugía cardíaca con circulación extracorpórea.

OBJECTIVE: To evaluate microcirculation in intermediate and high mortality risk patients undergoing cardiac surgery (CS) with cardiopulmonary bypass (CPB). PATIENTS AND METHODS: The study included 22 patients with a Euroscore >3. Using the Videomicroscopy Side Stream Dark Field system, and evaluation was made of, capillary density, proportion of perfused capillaries, density of perfused capillaries, microcirculatory flow index (MFI), and heterogeneity flow index. Three to five video sequences were recorded: after induction of anaesthesia (T1), at the beginning of the CPB (T2), before finalising CPB (T3), at the end of the surgery, and before the patient was transferred to Intensive Care Unit (T4). Mean arterial pressure decreased, while the blood lactate increased significantly, when comparing the initial and final values (P<.05). MFI increased significantly in T3 and T4 (P<.05) with regards to the initial values. When the patients with and without postoperative complications were compared, significant differences were found in, Euroscore, left ventricular ejection fraction, and MFI in T3. CONCLUSIONS: in patients with intermediate/high preoperative risk, CS and CBP can involve an increase in MFI and blood lactate at the end of the study. These alterations suggest the possibility of a functional microcirculatory shunt at tissue perfusion level, secondary to the surgical injury and the CPB. Further investigation is needed to have a better understanding of the mechanisms involved.

Partial protection and abomasal cytokine expression in sheep experimentally infected with Haemonchus contortus and pre-treated with Taenia hydatigena vesicular concentrate.

The abomasal expression of IL-2, IL-4, IL-6, IL-10 and IFNγ in lambs experimentally infected with Haemonchus contortus and its relationship to protection induced by a Taenia hydatigena larvae vesicular concentrate (ThLVC) were evaluated. The lambs that were only infected with H. contortus larvae showed a worm burden greater (p<0.05) than the lambs that received ThLVC prior to infection. Moreover, the lambs that received ThLVC showed a greater (p<0.05) number of blood eosinophils than the lambs that did not receive the ThLVC. In general, the lambs that received ThLVC prior to infection had a greater amount of eosinophils and mast cells and higher in situ expression of IFNγ, IL-2, IL-4, IL-6 and IL-10 in the abomasal wall than the lambs that were infected with H. contortus only or that received ThLVC (p<0.05) only. A higher expression of IL-2 and IFNγ in the submucosa compared to the abomasal mucosa and a higher expression of IL-4 in the abomasal mucosa compared to the submucosa was observed (p<0.05). These results suggest that there is a Th1 type response in the abomasal submucosa and a Th2 type response in in the abomasal mucosa. The amount of eosinophils and mast cells and the in situ expression of IFNγ, IL-2, IL-4 and IL-6 in the abomasal walls were negatively correlated with the worm burden (p<0.05). These results suggest that ThLVC is a non-specific immune stimulator for the abomasal immune response, and it is likely that the protection observed is the result of this effect.

Treatment of vitreomacular traction syndrome with autologous plasmin enzyme.

PURPOSE: To determine whether intravitreal injection of autologous plasmin enzyme (APE) is effective in vitreomacular traction syndrome (VMTS) by improving visual acuity and restoring macular morphology. METHODS: A prospective study of 11 consecutive patients diagnosed with VMTS in the Ophthalmology Department from January to May, 2011. INCLUSION CRITERIA: best corrected visual acuity (BCVA) less than 0.5, and vitreomacular attachment in foveal area resulting in macular thickness>250 microns diagnosed by optical coherence tomography (Cirrus OCT, Carl Zeiss Meditec, Inc, Oberkochen, Germany). EXCLUSION CRITERIA: active proliferative diabetic retinopathy, axial myopia>26mm, vitrectomy, glaucoma, previous intravitreal injections and previous rhegmatogenous detachment. One to 3 monthly intravitreal injections of 0.2ml of APE were applied, interrupting if posterior vitreous detachment was attained. Wilcoxon's test was used for statistical analysis. RESULTS: A total of 12 eyes of 11 patients were treated. A complete posterior vitreous detachment was achieved in 4 (33%) eyes at the end of the study, 2 of them with one injection, and 2 with 3 monthly injections. Improvement of BCVA was statistically significant (P=.017) and the decrease in central macular thickness also was statistically significant (P=.016). There was only one complication: intraocular hypertension after injection that subsided with a new paracentesis. CONCLUSIONS: Intravitreal APE injections avoided vitrectomy in VMTS in one in every 3 patients.