Direct measurement of pulse distortion near the zero-dispersion wavelength in an optical fiber by frequency-resolved optical gating

The technique of frequency-resolved optical gating is used to characterize the intensity and the phase of picosecond pulses after propagation through 700 m of fiber at close to the zero-dispersion wavelength. Using the frequency-resolved optical gating technique, we directly measure the severe temporal distortion resulting from the interplay between self-phase modulation and higher-order dispersion in this regime. The measured intensity and phase of the pulses after propagation are found to be in good agreement with the predictions of numerical simulations with the nonlinear Schrodinger equation. (C) 1997 Optical Society of America.

Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation

Dias RG, Alves MJ, Pereira AC, Rondon MU, dos Santos MR, Krieger JE, Krieger MH, Negrao CE. Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation. Physiol Genomics 37: 99-107, 2009. First published January 21, 2009; doi:10.1152/physiolgenomics.90368.2008.-The influence of Glu298Asp endothelial nitric oxide synthase (eNOS) polymorphism in exercise-induced reflex muscle vasodilatation is unknown. We hypothesized that nonexercising forearm blood flow (FBF) responses during handgrip isometric exercise would be attenuated in individuals carrying the Asp298 allele. In addition, these responses would be mediated by reduced eNOS function and NO-mediated vasodilatation or sympathetic vasoconstriction. From 287 volunteers previously genotyped, we selected 33 healthy individuals to represent three genotypes: Glu/Glu [n = 15, age 43 +/- 3 yr, body mass index (BMI) 22.9 +/- 0.3 kg/m(2)], Glu/Asp (n = 9, age 41 +/- 3 yr, BMI 23.7 +/- 1.0 kg/m(2)), and Asp/Asp (n = 9, age 40 +/- 4 yr, BMI 23.5 +/- 0.9 kg/m(2)). Heart rate (HR), mean blood pressure (MBP), and FBF (plethysmography) were recorded for 3 min at baseline and 3 min during isometric handgrip exercise. Baseline HR, MBP, FBF, and forearm vascular conductance (FVC) were similar among genotypes. FVC responses to exercise were significantly lower in Asp/Asp when compared with Glu/Asp and Glu/Glu (Delta = 0.07 +/- 0.14 vs. 0.64 +/- 0.20 and 0.57 +/- 0.09 units, respectively; P = 0.002). Further studies showed that intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA) did not change FVC responses to exercise in Asp/Asp, but significantly reduced FVC in Glu/Glu (Delta = 0.79 +/- 0.14 vs. 0.14 +/- 0.09 units). Thus the differences between Glu/Glu and Asp/Asp were no longer observed (P = 0.62). L-NMMA + phentolamine increased similarly FVC responses to exercise in Glu/Glu and Asp/Asp (P = 0.43). MBP and muscle sympathetic nerve activity increased significant and similarly throughout experimental protocols in Glu/Glu and Asp/Asp. Individuals who are homozygous for the Asp298 allele of the eNOS enzyme have attenuated nonexercising muscle vasodilatation in response to exercise. This genotype difference is due to reduced eNOS function and NO-mediated vasodilatation, but not sympathetic vasoconstriction.

IMAGE QUANTIFICATION FOR RADIATION DOSE CALCULATIONS-LIMITATIONS AND UNCERTAINTIES

Radiation dose calculations in nuclear medicine depend on quantification of activity via planar and/or tomographic imaging methods. However, both methods have inherent limitations, and the accuracy of activity estimates varies with object size, background levels, and other variables. The goal of this study was to evaluate the limitations of quantitative imaging with planar and single photon emission computed tomography (SPECT) approaches, with a focus on activity quantification for use in calculating absorbed dose estimates for normal organs and tumors. To do this we studied a series of phantoms of varying complexity of geometry, with three radionuclides whose decay schemes varied from simple to complex. Four aqueous concentrations of (99m)Tc, (131)I, and (111)In (74, 185, 370, and 740 kBq mL(-1)) were placed in spheres of four different sizes in a water-filled phantom, with three different levels of activity in the surrounding water. Planar and SPECT images of the phantoms were obtained on a modern SPECT/computed tomography (CT) system. These radionuclides and concentration/background studies were repeated using a cardiac phantom and a modified torso phantom with liver and ""tumor"" regions containing the radionuclide concentrations and with the same varying background levels. Planar quantification was performed using the geometric mean approach, with attenuation correction (AC), and with and without scatter corrections (SC and NSC). SPECT images were reconstructed using attenuation maps (AM) for AC; scatter windows were used to perform SC during image reconstruction. For spherical sources with corrected data, good accuracy was observed (generally within +/- 10% of known values) for the largest sphere (11.5 mL) and for both planar and SPECT methods with (99m)Tc and (131)I, but were poorest and deviated from known values for smaller objects, most notably for (111)In. SPECT quantification was affected by the partial volume effect in smaller objects and generally showed larger errors than the planar results in these cases for all radionuclides. For the cardiac phantom, results were the most accurate of all of the experiments for all radionuclides. Background subtraction was an important factor influencing these results. The contribution of scattered photons was important in quantification with (131)I; if scatter was not accounted for, activity tended to be overestimated using planar quantification methods. For the torso phantom experiments, results show a clear underestimation of activity when compared to previous experiment with spherical sources for all radionuclides. Despite some variations that were observed as the level of background increased, the SPECT results were more consistent across different activity concentrations. Planar or SPECT quantification on state-of-the-art gamma cameras with appropriate quantitative processing can provide accuracies of better than 10% for large objects and modest target-to-background concentrations; however when smaller objects are used, in the presence of higher background, and for nuclides with more complex decay schemes, SPECT quantification methods generally produce better results. Health Phys. 99(5):688-701; 2010

On the validity of the dispersion model of hepatic drug elimination when intravascular transit time densities are long-tailed

The dispersion model with mixed boundary conditions uses a single parameter, the dispersion number, to describe the hepatic elimination of xenobiotics and endogenous substances. An implicit a priori assumption of the model is that the transit time density of intravascular indicators is approximated by an inverse Gaussian distribution. This approximation is limited in that the model poorly describes the tail part of the hepatic outflow curves of vascular indicators. A sum of two inverse Gaussian functions is proposed as ail alternative, more flexible empirical model for transit time densities of vascular references. This model suggests that a more accurate description of the tail portion of vascular reference curves yields an elimination rate constant (or intrinsic clearance) which is 40% less than predicted by the dispersion model with mixed boundary conditions. The results emphasize the need to accurately describe outflow curves in using them as a basis for determining pharmacokinetic parameters using hepatic elimination models. (C) 1997 Society for Mathematical Biology.

Relative dispersion of intravascular transit times during isolated human limb perfusions for recurrent melanoma

Aims We have characterized the relative dispersion of vascular and extravascular markers in the limbs of three patients undergoing isolated limb perfusions with the cytotoxic melphalan for recurrent malignant melanoma both before and after melphalan dosing. Methods A bolus of injectate containing [Cr-51] labelled red blood cells, [C-14]-sucrose and [H-3]-water was injected into an iliac or femoral artery and outflow samples collected at 1 s intervals by a fraction collector. The radioactivity due to each isotype was analysed by either gamma [Cr-51] or beta [C-14 and H-3] counting. The moments of the outflow fraction-time profiles were estimated by a nonparametric (numerical integration) method and a parametric model (sum of two inverse Gaussian functions). Results The availability, mean transit time and normalised variance (CV2) obtained for labelled red blood cells, sucrose and water were similar before and after melphalan dosing and with the two methods of calculation but varied between the patients. Conclusions The vascular space is not well-stirred but characterized by a CV2 similar that reported previously for in situ rat hind limb and rat liver perfusions. A flow-limited blood-tissue exchange was observed for the permeating indicators. Administration of melphalan did not influence the distribution characteristics of the indicators.

Impulse-response studies on tracer doses of [C-14]lignocaine and its multiple metabolites in the perfused rat liver

The outflow-concentration-time profiles for lignocaine (lidocaine) and its metabolites have been measured after bolus impulse administration of [C-14]lignocaine into the perfused rat liver. Livers from female Sprague-Dawley rats were perfused in a once-through fashion with red-blood-cell-free Krebs-Henseleit buffer containing 0 or 2% bovine serum albumin. Perfusate flow rates of 20 and 30 mL min(-1) were used and both normal and retrograde flow directions were employed. Significant amounts of metabolite were detected in the effluent perfusate soon after lignocaine injection. The early appearance of metabolite contributed to bimodal outflow profiles observed for total C-14 radioactivity. The lignocaine outflow profiles were well characterized by the two-compartment dispersion model, with efflux rate << influx rate. The profiles for lignocaine metabolites were also characterized in terms of a simplified two-compartment dispersion model. Lignocaine was found to be extensively metabolized under the experimental conditions with the hepatic availability ranging between 0.09 and 0.18. Generally lignocaine and metabolite availability showed no significant change with alterations in perfusate flow rate from 20 to 30 mt min(-1) or protein content from 0 to 2%. A significant increase in lignocaine availability occurred when 1200 mu M unlabelled lignocaine was added to the perfusate. Solute mean transit times generally decreased with increasing flow rate and with increasing perfusate protein content. The results confirm that lignocaine pharmacokinetics in the liver closely follow the predictions of the well-stirred model. The increase in lignocaine availability when 1200 mu M unlabelled lignocaine was added to the perfusate is consistent with saturation of the hydroxylation metabolic pathways of lignocaine metabolism.

In situ apoptosis of adaptive immune cells and the cellular escape of rabies virus in CNS from patients with human rabies transmitted by Desmodus rotundus

The aim of the current study was to investigate the apoptosis of neurons, astrocytes and immune cells from human patients that were infected with rabies virus by vampire bats bite. Apoptotic neurons were identified by their morphology and immune cells were identified using double immunostaining. There were very few apoptotic neurons present in infected tissue samples, but there was an increase of apoptotic infiltrating CD4+ and TCD8+ adaptive immune cells in the rabies infected tissue. No apoptosis was present in NK, macrophage and astrocytes. The dissemination of the human rabies virus within an infected host may be mediated by viral escape of the virus from an infected cell and may involve an anti-apoptotic mechanism, which does not kill the neuron or pro-apoptosis of TCD4+ and TCD8+ lymphocytes and which allows for increased proliferation of the virus within the CNS by attenuation of the adaptive immune response. (C) 2011 Elsevier B.V. All rights reserved.

Effects of semen storage and separation techniques on sperm DNA fragmentation

Objective: To determine the effect of semen storage and separation techniques on sperm DNA fragmentation. Design: Controlled clinical study. Setting: An assisted reproductive technology laboratory. Patient(s): Thirty normoozospermic semen samples obtained from patients undergoing infertility evaluation. Intervention(s): One aliquot from each sample was immediately prepared (control) for the sperm chromatin dispersion assay (SCD). Aliquots used to assess storage techniques were treated in the following ways: snap frozen by liquid nitrogen immersion, slow frozen with Tris-yolk buffer and glycerol, kept on ice for 24 hours or maintained at room temperature for 4 and 24 hours. Aliquots used to assess separation techniques were processed by the following methods: washed and centrifuged in media, swim-up from washed sperm pellet, density gradient separation, density gradient followed by swim-up. DNA integrity was then measured by SCD. Main Outcome Measure(s): DNA fragmentation as measured by SCD. Result(s): There was no significant difference in fragmentation among the snap frozen, slow frozen, and wet-ice groups. Compared to other storage methods short-term storage at room temperature did not impact DNA fragmentation yet 24 hours storage significantly increased fragmentation. Swim-up, density gradient and density gradient/swim-up had significantly reduced DNA fragmentation levels compared with washed semen. Postincubation, density gradient/swim-up showed the lowest fragmentation levels. Conclusion(s): The effect of sperm processing methods on DNA fragmentation should be considered when selecting storage or separation techniques for clinical use. (Fertil Steril (R) 2010;94:2626-30. (C) 2010 by American Society for Reproductive Medicine.)

Serotonin and Sensitivity to Trauma-Related Exposure in Selective Serotonin Reuptake Inhibitors-Recovered Posttraumatic Stress Disorder

Background: Selective serotonin reuptake inhibitors (SSRIs) are first-line treatments for posttraumatic stress disorder (PTSD). Serotonergic (5HT) attenuation of stress sensitivity is postulated from SSRIs` effects in other anxiety disorders, and we studied this in PTSD. Methods: Ten patients with PTSD fully recovered on SSRIs (Clinical Global Impression Scale-I 1 and 2) were enrolled in the study. Patients were tested on two occasions I week apart; in each session, they received a drink containing large neutral amino acids (LNAAs) either with (sham tryptophan depletion [STD], control) or without (acute tryptophan depletion [ATD]) tryptophan. At 5.5 hours after the drink, subjects were exposed to a trauma-related exposure challenge. Self-reports of PTSD (visual analogue scales [VAS] and the Davidson Trauma Scale [DTSI), anxiety (Spielberger State Inventory [STAI] Form Y-1), and mood (Profile of Mood States [POMS]) were obtained. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure were also measured. Results: The trauma-related exposure challenge induced anxiety on both days, with more marked responses on the ATD day according to VAS, DTS, POMS, and DBP (p < .05). A trend of significance (.1 > p >.05) was observed for STAI Form Y-1, HR, and SBP. Conclusions: These data demonstrate that ATD accentuates responses to trauma-related stimuli in SSRI-recovered PTSD. They also suggest that SSRI-induced increases in serotonin function restrain PTSD symptoms, especially under provocation, supporting a role for serotonin in mediating stress resilience.

Water excitation MPRAGE: An alternative sequence for postcontrast imaging of the abdomen in noncooperative patients at 1.5 Tesla and 3.0 Tesla MRI

Purpose: To evaluate the diagnostic image quality of post-gadolinium water excitation-magnetization-prepared rapid gradient-echo (WE-MPRAGE) sequence in abdominal examinations of noncooperative patients at 1.5 Tesla (T) and 3.0T MRI. Materials and Methods: Eighty-nine consecutive patients (48 males and 41 females; mean age +/- standard deviation, 54.6 +/- 16.6 years) who had MRI examinations including postgadolinium WE-MPRAGE were included in the study. Of 89 patients, 33 underwent noncooperative protocol at 1.5T. 10 under-went noncooperative protocol at 3.0T, and 46 underwent cooperative protocol at 3.0T. Postgadolinium WE-MPRAGE, MPRAGE, and three-dimensional gradient-echo sequences of these three different groups were qualitatively evaluated for image quality, extent of artifacts, lesion conspicuity, and homogeneity of fat-attenuation by two reviewers retrospectively, independently, and blindly. The results were compared using Wilcoxon signed rank and Mann-Whitney U tests. Kappa statistics were used to measure the extent of agreement between the reviewers. Results: The average scores indicated that the images were diagnostic for WE-MPRAGE at 1.5T and 3.0T in noncooperative patients. WE-MPRAGE achieved homogenous fat-attenuation in 31/33 (94%) of noncooperative patients at 1.5T and 10/10 (100%) of noncooperative patients at 3.0T. WE-MPRAGE at 3.0T had better results for image quality, extent of artifacts, lesion conspicuity and homogeneity of fat-attenuation compared with WE-MPRAGE at 1.5T. in noncooperative patients (P = 0.0008, 0.0006, 0.0024, and 0.0042: respectively). Kappa statistics varied between 0.76 and 1.00, representing good to excellent agreement. Conclusion: WE-MPRAGE may be used as a T1-weighted postgadolinium fat-attenuated sequence in noncooperative patients, particularly at 3.0T MRI.

Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats

Rationale: Systemic administration of cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa, is able to attenuate cardiovascular and behavioral (freezing) changes induced by re-exposure to a context that had been previously paired with footshocks. The brain sites mediating this effect, however, remain unknown. The medial prefrontal cortex (mPFC) has been related to contextual fear conditioning. Objectives: (1) To verify, using c-Fos immunocytochemistry, if the mPFC is involved in the attenuation of contextual fear induced by systemic administration of CBD; (2) to investigate if direct microinjections of CBD into mPFC regions would also attenuate contextual fear. Results: Confirming previous results systemic administration of CBD (10 mg/kg) decreased contextual fear and associated c-Fos expression in the prefrontal cortex (prelimbic and infralimbic regions). The drug also attenuated c-Fos expression in the bed nucleus of the stria terminalis (BNST). Direct CBD (30 nmol) microinjection into the PL prefrontal cortex reduced freezing induced by re-exposure to the aversively conditioned context. In the infralimbic (IL) prefrontal cortex, however, CBD (30 nmol) produced an opposite result, increasing the expression of contextual fear conditioning. This result was confirmed by an additional experiment where the conditioning session was performed under a less aversive protocol. Conclusion: These results suggest that the PL prefrontal cortex may be involved in the attenuation of contextual fear induced by systemic injection of CBD. They also support the proposition that the IL and PL play opposite roles in fear conditioning. A possible involvement of the BNST in CBD effects needs to be further investigated. (C) 2009 Elsevier B.V. All rights reserved.

Ontogenetic role of angiontensin-converting enzyme in rats: Thirst and sodium appetite evaluation

We investigated the influence of captopril (an angiotensin converting enzyme inhibitor) treatment during pregnancy and lactation period on hydromineral balance of the male adult offspring, particularly, concerning thirst and sodium appetite. We did not observe significant alterations in basal hydromineral (water intake, 0.3 M NaCl intake, volume and sodium urinary concentration) or cardiovascular parameters in adult male rats perinatally treated with captopril compared to controls. However, male offspring rats that perinatally exposed to captopril showed a significant attenuation in water intake induced by osmotic stimulation, extracellular dehydration and beta-adrenergic stimulation. Moreover, captopril treatment during perinatal period decreased the salt appetite induced by sodium depletion. This treatment also attenuated thirst and sodium appetite aroused during inhibition of peripheral angiotensin 11 generation raised by low concentration of captopril in the adult offspring. Interestingly. perinatal exposure to captopril did not alter water or salt intake induced by i.c.v. administration of angiotensin I or angiotensin II. These results showed that chronic inhibition of angiotensin converting enzyme during pregnancy and lactation modifies the regulation of induced thirst and sodium appetite in adulthood. (C) 2009 Elsevier Inc. All rights reserved.

Modulation of Auditory and Visual Processing by Delta-9-Tetrahydrocannabinol and Cannabidiol: an fMRI Study

Although the effects of cannabis on perception are well documented, little is known about their neural basis or how these may contribute to the formation of psychotic symptoms. We used functional magnetic resonance imaging (fMRI) to assess the effects of Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) during visual and auditory processing in healthy volunteers. In total, 14 healthy volunteers were scanned on three occasions. Identical 10mg THC, 600mg CBD, and placebo capsules were allocated in a balanced double-blinded pseudo-randomized crossover design. Plasma levels of each substance, physiological parameters, and measures of psychopathology were taken at baseline and at regular intervals following ingestion of substances. Volunteers listened passively to words read and viewed a radial visual checkerboard in alternating blocks during fMRI scanning. Administration of THC was associated with increases in anxiety, intoxication, and positive psychotic symptoms, whereas CBD had no significant symptomatic effects. THC decreased activation relative to placebo in bilateral temporal cortices during auditory processing, and increased and decreased activation in different visual areas during visual processing. CBD was associated with activation in right temporal cortex during auditory processing, and when contrasted, THC and CBD had opposite effects in the right posterior superior temporal gyrus, the right-sided homolog to Wernicke`s area. Moreover, the attenuation of activation in this area (maximum 61, -15, -2) by THC during auditory processing was correlated with its acute effect on psychotic symptoms. Single doses of THC and CBD differently modulate brain function in areas that process auditory and visual stimuli and relate to induced psychotic symptoms. Neuropsychopharmacology (2011) 36, 1340-1348; doi:10.1038/npp.2011.17; published online 16 March 2011

Mesial temporal lobe epilepsy: Clinical and neuropathologic findings of familial and sporadic forms

Purpose: To evaluate the clinical and hippocampal histological features of patients with mesial temporal lobe epilepsy (MTLE) in both familial (FMTLE) and sporadic (SMTLE) forms. Methods: Patients with FMTLE (n = 20) and SMTLE (n = 39) who underwent surgical treatment for refractory seizures were studied at the University of Sao Paulo School of Medicine at Ribeirao Preto. FMTLE was defined when at least two individuals in a family had clinical diagnosis of MTLE. Hippocampi from all patients were processed for Nissl/HE and Timm`s stainings. Both groups were compared for clinical variables, hippocampal cell densities, and intensity of supragranular mossy fiber staining. Results: There were no significant differences between FMTLE and SMTLE groups in the following: age at the surgery, age of first usual epileptic seizure, history of initial precipitating injury (IPI), age of IPI, latent period, ictal and interictal video-EEG patterns, presence of hippocampal atrophy and signal changes at MRI, and postoperative outcome. In addition, no differences were found in cell densities in hippocampal cornu ammonis subfields (CA1, CA2, CA3, CA4), fascia dentata, polymorphic region, subiculum, prosubiculum, and presubiculum. However, patients with SMTLE had greater intensity of mossy fiber Timm`s staining in the fascia dentata-inner molecular layer (p < 0.05). Discussion: Patients with intractable FMTLE present a clinical profile and most histological findings comparable to patients with SMTLE. Interestingly, mossy fiber sprouting was less pronounced in patients with FMTLE, suggesting that, when compared to SMTLE, patients with FMTLE respond differently to plastic changes plausibly induced by cell loss, neuronal deafferentation, or epileptic seizures.