Modulation transfer function and optical quality after bilateral implantation of a+3.00 D versus a+4.00 D multifocal intraocular lens

PURPOSE: To determine whether the improvement in intermediate vision after bilateral implantation of an aspheric multifocal intraocular lens (IOL) with a +3.00 diopter (D) addition (add) occurs at the expense of optical quality compared with the previous model with a +4.00 D add. SETTING: Department of Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil. DESIGN: Prospective randomized double-masked comparative clinical trial. METHODS: One year after bilateral implantation of Acrysof Restor SN6AD1 +3.00 D IOLs or Acrysof Restor SN6AD3 +4.00 D IOLs, optical quality was evaluated by analyzing the in vivo modulation transfer function (MTF) and point-spread function (expressed as Strehl ratio). The Strehl ratio and MTF curve with a 4.0 pupil and a 6.0 mm pupil were measured by dynamic retinoscopy aberrometry. The uncorrected and corrected distance visual acuities at 4 m, uncorrected and distance-corrected near visual acuities at 40 cm, and uncorrected and distance-corrected intermediate visual acuities at 50 cm, 60 cm, and 70 cm were measured. RESULTS: Both IOL groups comprised 40 eyes of 20 patients. One year postoperatively, there were no statistically significant between-group differences in the MTF or Strehl ratio with either pupil size. There were no statistically significant between-group differences in distance or near visual acuity. Intermediate visual acuity was significantly better in the +3.00 D IOL group. CONCLUSION: Results indicate that the improvement in intermediate vision in eyes with the aspheric multifocal +3.00 D add IOL occurred without decreasing optical quality over that with the previous version IOL with a +4.00 D add.

Modulation of Maternal Immune System During Pregnancy in the Cow

There is a molecular crosstalk between the trophoblast and maternal immune cells of bovine endometrium. The uterine cells are able to secrete cytokine/chemokines to either induce a suppressive environment for establishment of the pregnancy or to recruit immune cells to the endometrium to fight infections. Despite morphological differences between women and cows, mechanisms for immune tolerance during pregnancy seem to be conserved. Mechanisms for uterine immunesuppression in the cow include: reduced expression of major histocompatability proteins by the trophoblast; recruitment of macrophages to the pregnant endometrium; and modulation of immune-related genes in response to the presence of the conceptus. Recently, an eGFP transgenic cloned embryo model developed by our group showed that there is modulation of foetal proteins expressed at the site of syncytium formation, suggesting that foetal cell can regulate not only by the secretion of specific factors such as interferon-tau, but also by regulating their own protein expression to avoid excessive maternal recognition by the local immune system. Furthermore, foetal DNA can be detected in the maternal circulation; this may reflect the occurrence of an invasion of trophoblast cells and/or their fragment beyond the uterine basement membrane in the cow. In fact, the newly description of exosome release by the trophoblast cell suggests that could be a new fashion of maternal-foetal communication at the placental barrier. Additionally, recent global transcriptome studies on bovine endometrium suggested that the immune system is aware, from an immunological point of view, of the presence of the foetus in the cow during early pregnancy.

CD25(+) T cell depletion impairs murine squamous cell carcinoma development via modulation of antitumor immune responses

Squamous cell carcinoma (SCC) constitutes a microenvironment that could modulate the antitumor immune response. Also, tumor-infiltrating lymphocytes are believed to play complex regulatory roles in antitumor immunity against SCC. The presence of regulatory T cells (Tregs) has been associated with the suppression of tumor-reactive T cells. However, the underlying mechanism for this T cell dysfunction is not clear. We used a multistage model of SCC to examine the role of Treg cells during tumor development. 7,12-dimethylbenz[a]-anthracene/phorbol 12-myristate 13-acetate treatment and systemic depletion of Treg cells using an anti-CD25 monoclonal antibody (PC61) resulted in a decrease in the number and incidence of papilloma. Furthermore, CD25 depletion increased the proportion of CD8(+) and CD4(+) T cells that were isolated from tumor lesions. The levels of interleukin (IL)-1 beta, IL-10, IL-12, IL-13, interferon-gamma, transforming growth factor-beta and tumor necrosis factor-alpha, but not IL-17, were increased in the tumor microenvironment after Treg depletion. Therefore, our results indicated involvement of CD25(+) T cells in SCC development and in the suppression of the inflammatory immune response.

Acute exercise adjustments of cardiovascular autonomic control in diabetic rats

Introduction: We evaluated the role of cardiovascular autonomic changes in hemodynamics at rest and in response to exercise in streptozotocin-induced diabetic rats. Methods: Male Wistar rats were divided into nondiabetic (ND, n = 8) and diabetic (D, n = 8) groups. Arterial pressure signals were recorded in the basal state and after atropine or propranolol injections at rest, during exercise and during recovery. Results: At rest, vagal tonus was reduced in D (37 +/- 3 bpm) in comparison with the ND group (61 +/- 9 bpm). Heart rate during exercise was lower in D in relation to ND rats associated with reduced vagal withdrawal in the D group. The D rats had an increase in vagal tonus in the recovery period (49 +/- 6 bpm). Conclusions: Exercise-induced hemodynamic adjustment impairment in diabetic rats was associated with reduced cardiac vagal control. The vagal dysfunction was attenuated after aerobic exercise, reinforcing the positive role of this approach in the management of cardiovascular risk in diabetics. Muscle Nerve 46: 96101, 2012

KCNQ Channels Determine Serotonergic Modulation of Ventral Surface Chemoreceptors and Respiratory Drive

Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing in response to CO2/H+ changes. Their activity is also sensitive to neuromodulatory inputs from multiple respiratory centers, and thus they serve as a key nexus of respiratory control. However, molecular mechanisms that control their activity and susceptibility to neuromodulation are unknown. Here, we show in vitro and in vivo that KCNQ channels are critical determinants of RTN neural activity. In particular, we find that pharmacological block of KCNQ channels (XE991, 10 mu M) increased basal activity and CO2 responsiveness of RTN neurons in rat brain slices, whereas KCNQ channel activation (retigabine, 2-40 mu M) silenced these neurons. Interestingly, we also find that KCNQ and apamin-sensitive SK channels act synergistically to regulate firing rate of RTN chemoreceptors; simultaneous blockade of both channels led to a increase in CO2 responsiveness. Furthermore, we also show that KCNQ channels but not SK channels are downstream effectors of serotonin modulation of RTN activity in vitro. In contrast, inhibition of KCNQ channel did not prevent modulation of RTN activity by Substance P or thyrotropin-releasing hormone, previously identified neuromodulators of RTN chemoreception. Importantly, we also show that KCNQ channels are critical for RTN activity in vivo. Inhibition of KCNQ channels lowered the CO2 threshold for phrenic nerve discharge in anesthetized rats and decreased the ventilatory response to serotonin in awake and anesthetized animals. Given that serotonergic dysfunction may contribute to respiratory failure, our findings suggest KCNQ channels as a new therapeutic avenue for respiratory complications associated with multiple neurological disorders.

Monosodium glutamate neonatal treatment induces cardiovascular autonomic function changes in rodents

OBJECTIVES: The aim of this study was to evaluate cardiovascular autonomic function in a rodent obesity model induced by monosodium glutamate injections during the first seven days of life. METHOD: The animals were assigned to control (control, n = 10) and monosodium glutamate (monosodium glutamate, n = 13) groups. Thirty-three weeks after birth, arterial and venous catheters were implanted for arterial pressure measurements, drug administration, and blood sampling. Baroreflex sensitivity was evaluated according to the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine infusion, respectively. Sympathetic and vagal effects were determined by administering methylatropine and propranolol. RESULTS: Body weight, Lee index, and epididymal white adipose tissue values were higher in the monosodium glutamate group in comparison to the control group. The monosodium glutamate-treated rats displayed insulin resistance, as shown by a reduced glucose/insulin index (-62.5%), an increased area under the curve of total insulin secretion during glucose overload (39.3%), and basal hyperinsulinemia. The mean arterial pressure values were higher in the monosodium glutamate rats, whereas heart rate variability (>7 times), bradycardic responses (>4 times), and vagal (similar to 38%) and sympathetic effects (similar to 36%) were reduced as compared to the control group. CONCLUSION: Our results suggest that obesity induced by neonatal monosodium glutamate treatment impairs cardiac autonomic function and most likely contributes to increased arterial pressure and insulin resistance.

Transcriptome Analysis of Renal Ischemia/Reperfusion Injury and Its Modulation by Ischemic Pre-Conditioning or Hemin Treatment

Ischemia/reperfusion injury (IRI) is a leading cause of acute renal failure. The definition of the molecular mechanisms involved in renal IRI and counter protection promoted by ischemic pre-conditioning (IPC) or Hemin treatment is an important milestone that needs to be accomplished in this research area. We examined, through an oligonucleotide microarray protocol, the renal differential transcriptome profiles of mice submitted to IRI, IPC and Hemin treatment. After identifying the profiles of differentially expressed genes observed for each comparison, we carried out functional enrichment analysis to reveal transcripts putatively involved in potential relevant biological processes and signaling pathways. The most relevant processes found in these comparisons were stress, apoptosis, cell differentiation, angiogenesis, focal adhesion, ECM-receptor interaction, ion transport, angiogenesis, mitosis and cell cycle, inflammatory response, olfactory transduction and regulation of actin cytoskeleton. In addition, the most important overrepresented pathways were MAPK, ErbB, JAK/STAT, Toll and Nod like receptors, Angiotensin II, Arachidonic acid metabolism, Wnt and coagulation cascade. Also, new insights were gained about the underlying protection mechanisms against renal IRI promoted by IPC and Hemin treatment. Venn diagram analysis allowed us to uncover common and exclusively differentially expressed genes between these two protective maneuvers, underscoring potential common and exclusive biological functions regulated in each case. In summary, IPC exclusively regulated the expression of genes belonging to stress, protein modification and apoptosis, highlighting the role of IPC in controlling exacerbated stress response. Treatment with the Hmox1 inducer Hemin, in turn, exclusively regulated the expression of genes associated with cell differentiation, metabolic pathways, cell cycle, mitosis, development, regulation of actin cytoskeleton and arachidonic acid metabolism, suggesting a pleiotropic effect for Hemin. These findings improve the biological understanding of how the kidney behaves after IRI. They also illustrate some possible underlying molecular mechanisms involved in kidney protection observed with IPC or Hemin treatment maneuvers.

Thyroid hormones are involved in 5 '-nucleotidase modulation in soluble fraction of cardiac tissue

Aims: To investigate the role of TH (thyroid hormones) in 5'-nucleotidase activity and expression in cardiac soluble fraction (SF). Main methods: Male Wistar rats received daily injections of 14 (10, 25 or 50 mu g T4/100 g body weight) for 14 days to develop a hyperthyroidism condition. Thyroidectomy was performed in other animals to mimic hypothyroidism, and 14 days after surgery they were submitted to TH replacement therapy. Key findings: T4 reduced the 5'-nucleotidase activity (T4-25. P<0.05 and 14-50, P<0.01) in the SF. Conversely, hypothyroidism significantly increased the 5'-nucleotidase activity in this fraction (P<0.001) and TH replacement therapy reversed the latter result (P<0.001 compared to hypothyroid group). The analysis of protein expression in the SF showed that 5'-nucleotidase was more expressed in hypothyroid than in the control group and that the phosphorylated state of PKC observed in this condition may contribute to a possible mechanism of 5'-nucleotidase modulation by thyroid status. Significance: Taken together, these data reveal that TH can influence adenosine production by modulating 5'-nucleotidase activity and expression, which may contribute to the cardioprotective effect and the maintenance of cardiac function under TH privation. (C) 2012 Elsevier Inc. All rights reserved.

Opposing Roles for Cannabinoid Receptor Type-1 (CB1) and Transient Receptor Potential Vanilloid Type-1 Channel (TRPV1) on the Modulation of Panic-Like Responses in Rats

The midbrain dorsal periaqueductal gray (dPAG) has an important role in orchestrating anxiety-and panic-related responses. Given the cellular and behavioral evidence suggesting opposite functions for cannabinoid type 1 receptor (CB1) and transient receptor potential vanilloid type-1 channel (TRPV1), we hypothesized that they could differentially influence panic-like reactions induced by electrical stimulation of the dPAG. Drugs were injected locally and the expression of CB1 and TRPV1 in this structure was assessed by immunofluorescence and confocal microscopy. The CB1-selective agonist, ACEA (0.01, 0.05 and 0.5 pmol) increased the threshold for the induction of panic-like responses solely at the intermediary dose, an effect prevented by the CB1-selective antagonist, AM251 (75 pmol). Panicolytic-like effects of ACEA at the higher dose were unmasked by pre-treatment with the TRPV1 antagonist capsazepine (0.1 nmol). Similarly to ACEA, capsazepine (1 and 10 nmol) raised the threshold for triggering panic-like reactions, an effect mimicked by another TRPV1 antagonist, SB366791 (1 nmol). Remarkably, the effects of both capsazepine and SB366791 were prevented by AM251 (75 pmol). These pharmacological data suggest that a common endogenous agonist may have opposite functions at a given synapse. Supporting this view, we observed that several neurons in the dPAG co-expressed CB1 and TRPV1. Thus, the present work provides evidence that an endogenous substance, possibly anandamide, may exert both panicolytic and panicogenic effects via its actions at CB1 receptors and TRPV1 channels, respectively. This tripartite set-point system might be exploited for the pharmacotherapy of panic attacks and anxiety-related disorders. Neuropsychopharmacology (2012) 37, 478-486; doi:10.1038/npp.2011.207; published online 21 September 2011

Neutrophil dysfunction induced by hyperglycemia: modulation of myeloperoxidase activity

Our data suggest that impaired activity of myeloperoxidase (MPO) may play an important role in the dysfunction of neutrophils from hyperglycemic rats. Neutrophil biochemical pathways include the NADPH oxidase system and the MPO enzyme. They both play important role in the killing function of neutrophils. The effect of hyperglycemia on the activity of these enzymes and the consequences with regard to Candida albicans phagocytosis and the microbicidal property of rat peritoneal neutrophils is evaluated here. The NADPH oxidase system activity was measured using chemiluminescence and cytochrome C reduction assays. MPO activity was measured by monitoring HOCl production, and MPO protein expression was analysed using Western blot and immunofluorescence. C. albicans phagocytosis and death were evaluated by optical microscopy using the MayGrunwaldGiemsa staining method. ROS generation kinetic was slightly delayed in the diabetic group. MPO expression levels were higher in diabetic neutrophils; however, MPO activity was decreased in these same neutrophils compared with the controls. C. albicans phagocytosis and killing were lower in the diabetic neutrophils. Based on our experimental model, the phagocytic and killing functions of neutrophil phagocytosis are impaired in diabetic rats because of the decreased production of HOCl, highlighting the importance of MPO in the microbicidal function of neutrophils. Copyright (c) 2012 John Wiley & Sons, Ltd.

Medial prefrontal cortex endocannabinoid system modulates baroreflex activity through CB1 receptors

Ferreira-Junior NC, Fedoce AG, Alves FHF, Correa FMA, Resstel LBM. Medial prefrontal cortex endocannabinoid system modulates baroreflex activity through CB1 receptors. Am J Physiol Regul Integr Comp Physiol 302: R876-R885, 2012. First published December 28, 2011; doi: 10.1152/ajpregu.00330.2011.-Neural reflex mechanisms, such as the baroreflex, are involved in the regulation of cardiovascular system activity. Previous results from our group (Resstel LB, Correa FM. Medial prefrontal cortex NMDA receptors and nitric oxide modulate the parasympathetic component of the baroreflex. Eur J Neurosci 23: 481-488, 2006) have shown that glutamatergic synapses in the ventral portion of the medial prefrontal cortex (vMPFC) modulate baroreflex activity. Moreover, glutamatergic neurotransmission in the vMPFC can be modulated by the endocannabinoids system (eCBs), particularly the endocannabinoid anandamide, through presynaptic CB1 receptor activation. Therefore, in the present study, we investigated eCBs receptors that are present in the vMPFC, and more specifically whether CB1 receptors modulate baroreflex activity. We found that bilateral microinjection of the CB1 receptor antagonist AM251 (100 or 300 pmol/200 nl) into the vMPFC increased baroreflex activity in unanesthetized rats. Moreover, bilateral microinjection of either the anandamide transporter inhibitor AM404 (100 pmol/200 nl) or the inhibitor of the enzyme fatty acid amide hydrolase that degrades anandamide, URB597 (100 pmol/200 nl), into the MPFC decreased baroreflex activity. Finally, pretreatment of the vMPFC with an ineffective dose of AM251 (10 pmol/200 nl) was able to block baroreflex effects of both AM404 and URB597. Taken together, our results support the view that the eCBs in the vMPFC is involved in the modulation of baroreflex activity through the activation of CB1 receptors, which modulate local glutamate release.

Muscarinic and Nicotinic Modulation of Thalamo-Prefrontal Cortex Synaptic Pasticity In Vivo

The mediodorsal nucleus of the thalamus (MD) is a rich source of afferents to the medial prefrontal cortex (mPFC). Dysfunctions in the thalamo-prefrontal connections can impair networks implicated in working memory, some of which are affected in Alzheimer disease and schizophrenia. Considering the importance of the cholinergic system to cortical functioning, our study aimed to investigate the effects of global cholinergic activation of the brain on MD-mPFC synaptic plasticity by measuring the dynamics of long-term potentiation (LTP) and depression (LTD) in vivo. Therefore, rats received intraventricular injections either of the muscarinic agonist pilocarpine (PILO; 40 nmol/mu L), the nicotinic agonist nicotine (NIC; 320 nmol/mu L), or vehicle. The injections were administered prior to either thalamic high-frequency (HFS) or low-frequency stimulation (LFS). Test pulses were applied to MD for 30 min during baseline and 240 min after HFS or LFS, while field postsynaptic potentials were recorded in the mPFC. The transient oscillatory effects of PILO and NIC were monitored through recording of thalamic and cortical local field potentials. Our results show that HFS did not affect mPFC responses in vehicle-injected rats, but induced a delayed-onset LTP with distinct effects when applied following PILO or NIC. Conversely, LFS induced a stable LTD in control subjects, but was unable to induce LTD when applied after PILO or NIC. Taken together, our findings show distinct modulatory effects of each cholinergic brain activation on MD-mPFC plasticity following HFS and LFS. The LTP-inducing action and long-lasting suppression of cortical LTD induced by PILO and NIC might implicate differential modulation of thalamo-prefrontal functions under low and high input drive.

Induction of Psychosis by Delta 9-Tetrahydrocannabinol Reflects Modulation of Prefrontal and Striatal Function During Attentional Salience Processing

Context: The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing. Objective: To examine the effects of Delta 9-tetrahydrocannabinol (Delta 9-THC) and cannabidiol (CBD) on regional brain function during salience processing. Design: Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of Delta 9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli. Setting: University center. Participants: Fifteen healthy men with minimal previous cannabis use. Main Outcome Measures: Symptom ratings, task performance, and regional brain activation. Results: During the processing of oddball stimuli, relative to placebo, Delta 9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. Delta 9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of Delta 9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of Delta 9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation. Conclusions: Delta 9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders.

Simplified approach to low-cost multiparameter monitoring based on low frequency polarization modulation

We experimentally revisit a technique of low-cost multiparameter monitor for optical performance monitoring based on low frequency polarization modulation. A simplified calibration procedure, which significantly reduces the mathematical complexity and processing effort is proposed. Validation is achieved by carrying out relative optical power, wavelength, and differential group delay measurements. (C) 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 54:18201824, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.26956

Experimental gestational hypothyroidism evokes hypertension in adult offspring rats

Gestational hypothyroidism is a prevalent disorder in pregnant women. We aimed to investigate the impact of experimental gestational hypothyroidism (EGH) on cardiovascular and autonomic nervous systems (ANS) in the offspring of rats. EGH was induced with methimazole (MMI) 0.02% in drinking water from day 9 of gestation until birth. Sixty day old offspring from MMI-treated dams (OMTD, n = 13) or water-treated dams (OWTD, n = 13) had femoral arteries surgically assessed for the measurements of heart rate (HR), mean (MAP), systolic (SAP) and diastolic arterial pressure (DAP), and spontaneous baroreflex sensitivity (BRS). To investigate the balance of ANS, we established the high (HF) and low frequency (LF) bands of pulse interval (PI) and LF band of SAP spectrum. OMTD had increased MAP (130.2 +/- 2.0 vs 108.8 +/- 3.0 mm Hg, p<0.001), SAP (157.3 +/- 2.9 vs 135.7 +/- 4.5 mm Hg, p<0.001) and DAP (109.7 +/- 1.9 vs 88.4 +/- 2.6 mm Hg, p<0.001) when compared to OWED, and had lower HR (355.1 +/- 8.9 vs 386.8 +/- 9.2 bpm, p<0.05). After spectral analysis of PI and SAP, only LF band of SAP spectrum was higher (7.2 +/- 0.8 vs 4.0 +/- 0.6 mm Hg-2, p<0.01) in OMTD under spontaneous condition. Despite bradycardia, EGH promotes spontaneous hypertension in 60 day old offspring, probably due to increased sympathetic modulation of vessels, which is suggested by the higher LF of SAP. These findings suggest a critical role of maternal THs in the development of fetal cardiovascular and autonomic nervous systems. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.