Dynamics of adaptive and innate immunity in patients treated during primary human immunodeficiency virus infection: results from Maraviroc in HIV Acute Infection (MAIN) randomized clinical trial.

We evaluated the dynamics of innate and adaptive immunity in patients treated with combined antiretroviral therapy (cART) during primary human immunodeficiency virus infection (PHI), enrolled in a prospective randomized trial (MAIN, EUDRACT 2008-007004-29). After 48 weeks of cART, we documented a reduction in activated B cells and CD8(+) T cells. Natural killer cell and dendritic cell frequencies were measured and a decrease in CD16(+) CD56(dim) with a reciprocal rise in CD56(high) natural killer cells and an increase in myeloid and plasmacytoid dendritic cells were recorded. In conclusion, 48 weeks of cART during PHI showed significant benefits for both innate and adaptive immunity.

Maraviroc 150 mg daily plus lopinavir/ritonavir, a nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimen for HIV-infected naive patients: 48-week final results of VEMAN study.

Non-conventional strategies with nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimens in antiretroviral naive human immunodeficiency virus (HIV) -infected patients have been explored in clinical trials. A prospective, open-label, randomized (1:1), multicentre, proof-of-concept trial (VEMAN study, EUDRACT number 2008-006287-11) was conducted assigning HIV-infected naive patients to once-daily maraviroc plus lopinavir/ritonavir (MVC group) or to tenofovir/emtricitabine plus lopinavir/ritonavir (TDF/FTC group). Clinical and laboratory data were collected at baseline, and after 4, 12, 24, 36 and 48 weeks with the objective to evaluate the 48-week virological and immunological efficacy. HIV-1 DNA load and CD4(+) T-cell subsets were analysed on frozen peripheral blood mononuclear cells collected at baseline, 4 and 48 weeks to explore the trend in HIV reservoirs. Fifty patients were randomized and included in the analysis. During follow up, HIV-1 RNA decreased similarly in both groups and, at week 48, all patients in the MVC group and 22/24 (96%) in the TDF/FTC group had < 50 copies/ml of HIV-1 RNA. CD4(+) trend during follow up was higher in maraviroc-treated patients (MVC group: 286 (183-343) versus TDF/FTC group: 199 (125-285); Mann-Whitney U-test: p 0.033). A significant 48-week increase of CCR5(+) CD4(+) T cells and CD4(+) effector memory cells was observed among maraviroc-treated patients (Wilcoxon signed rank test: p 0.016 and p 0.007, respectively). No significant variations were found in naive and central memory CD4(+) T cells. Among naive patients with an R5 virus, treatment with maraviroc and lopinavir/ritonavir was shown to provide a virological response compared to a triple therapy and a greater immunological benefit.

" The times they aren't a-changin' " rTMS does not affect basic mechanisms of temporal discrimination: a pilot study with ERPs.

In time processing, the role of different cortical areas is still under investigation. Event-related potentials (ERPs) represent valuable indices of neural timing mechanisms in the millisecond-to-second domain. We used an interference approach by repetitive TMS (rTMS) on ERPs and behavioral performance to investigate the role of different cortical areas in processing basic temporal information. Ten healthy volunteers were requested to decide whether time intervals between two tones (S1-S2, probe interval) were shorter (800ms), equal to, or longer (1200ms) than a previously listened 1000-ms interval (target interval) and press different buttons accordingly. This task was performed at the baseline and immediately after a 15-min-long train of 1-Hz rTMS delivered over the supplementary motor area, right posterior parietal cortex, right superior temporal gyrus, or an occipital control area. Task accuracy, reaction time, and ERPs during (contingent negative variation, CNV) and after the presentation of probe intervals were analyzed. At the baseline, CNV amplitude was modulated by the duration of the probe interval. RTMS had no significant effect on behavioral or ERP measures. These preliminary data suggest that stimulated cortical areas are less crucially involved than other brain regions (e.g. subcortical structures) in the explicit discrimination of auditory time intervals in the range of hundreds of milliseconds.

Prognostic prediction ability of postoperative multifocal ERG after vitrectomy for diabetic macular edema.

PURPOSE: Diabetic macular edema (DME) causes visual loss in diabetic patients. Multifocal electroretinograms (mfERGs) have been used to assess macular function pre- and postvitrectomy for DME. METHODS: A standard three-port pars plana vitrectomy with peeling of inner limiting membrane was performed in 25 eyes of 21 patients (13 male, 8 female) with DME. For each patient, visual acuity examination, measure of retinal thickness (using optical coherence tomography), and mfERGs were performed before and 1 week, 1 month, 3 months, and 6 months after vitrectomy. RESULTS: Mean postoperative visual acuity was significantly improved (p<0.05, t test), with mean increase of 0.17 logMAR units; mean retinal thickness was significantly (p<0.001) decreased after surgery (from 537 microm to 298 microm). The increase of normalized amplitude of central ring was not significant; the mean P1 wave-amplitude increased from 0.33 to 0.40 mV; mean P1 wave-implicit time decreased 2.88 ms. We divided the patients into two groups: Group 1 (13 eyes), in which the visual recovery was less than 0.20 logMAR, and Group 2 (12 eyes), in which the visual recovery was greater than 0.20 logMAR. ERG results were statistically significantly different between the groups (p<0.025), when we consider the response recorded from the central ring. In Group 2 there is a marked reduction in implicit time of both ERGs waves, which was statistically significant for N1 wave (p=0.01). The changes of parameters of mfERG observed 6 months after surgery were consistent with those recorded just 1 week after surgery. CONCLUSIONS: Multifocal electroretinogram can be useful to predict functional prognosis in patients with diabetes who underwent vitrectomy for diabetic macular edema.

[Gastrointestinal stromal tumors: five case reports and review of the literature]. / Tumori stromali gastrointestinali: cinque casi clinici e revisione della letteratura.

Being a rare entity, GISTs represents the most common subset of mesenchymal tumours that arise from the digestive tract. Their immunohistochemical and histopathologic features distinguish them from other gastrointestinal mesenchymal neoplasms. These tumours have been the matter of considerable debate in the literature regarding their histogenesis, criteria for diagnosis, prognostic features and treatment. GISTs express Kit protein that not only is a marker for diagnosis but has also permitted to identify a specific medical treatment. The exceptional interest aroused in the literature leads us to make a review about this subject reporting five cases treated in the last 2 years.

Functional significance and induction by solar radiation of ultraviolet-absorbing sunscreens in field-grown soybean crops.

Colorless phenylpropanoid derivatives are known to protect plants from ultraviolet (UV) radiation, but their photoregulation and physiological roles under field conditions have not been investigated in detail. Here we describe a fast method to estimate the degree of UV penetration into photosynthetic tissue, which is based on chlorophyll fluorescence imaging. In Arabidopsis this technique clearly separated the UV-hypersensitive transparent testa (tt) tt5 and tt6 mutants from the wild type (WT) and tt3, tt4, and tt7 mutants. In field-grown soybean (Glycine max), we found significant differences in UV penetration among cultivars with different levels of leaf phenolics, and between plants grown under contrasting levels of solar UV-B. The reduction in UV penetration induced by ambient UV-B had direct implications for DNA integrity in the underlying leaf tissue; thus, the number of cyclobutane pyrimidine dimers caused by a short exposure to solar UV-B was much larger in leaves with high UV transmittance than in leaves pretreated with solar UV-B to increase the content phenylpropanoids. Most of the phenylpropanoid response to solar UV in field-grown soybeans was induced by the UV-B component (lambda

Mediastinal arteriovenous fistulae in the adult: case report and review of the literature.

An adult with an asymptomatic mediastinal arterio-venous fistula is presented. The diagnosis was established using angiography and oximetry after noninvasive imaging failed to identify the source of a continuous murmur. The literature is reviewed.

Quazepam and flurazepam: differential pharmacokinetic and pharmacodynamic characteristics.

Quazepam and flurazepam share pharmacokinetic properties that result in prevention of early-morning insomnia, daytime rebound anxiety, and withdrawal rebound insomnia. Yet sleep laboratory and performance studies demonstrated that during a 1- to 4-week administration period quazepam had a low potential for causing daytime drowsiness or impairment. This profile may be related to several factors, such as differences in quazepam's metabolic pathways; plasma pharmacokinetics; rate of brain uptake, redistribution, and clearance; as well as differences in receptor binding and kinetics.

A comparison of sodium bicarbonate and sodium lactate infusion in the induction of panic attacks.

Infusion of sodium lactate has been shown by a number of investigators to induce panic in patients with panic disorder, but the pathophysiology underlying this phenomenon is unknown. One theory to explain lactate's anxiety-producing effects involves its ability to induce alkalosis because of metabolic conversion to bicarbonate. To test this hypothesis, we administered both sodium lactate and sodium bicarbonate infusions in counterbalanced order to patients with panic disorder. Thirteen of 22 subjects panicked in response to lactate and nine of 20 subjects panicked in response to bicarbonate. Although the rate of panic between the two infusion responses was not significantly different, several aspects of response to the two infusions indicated that lactate may be a more potent producer of anxiety than bicarbonate. An unexpected finding was that bicarbonate panickers had a reduction in arterial carbon dioxide pressure during the infusion, while bicarbonate nonpanickers had an increase in arterial carbon dioxide pressure during the infusion. Induction of hyperventilation and subsequent hypocapnia appears to be a common denominator between lactate- and bicarbonate-induced panic.

Androgen control of an inhibitory modulator of phosphodiesterase in rat epididymis and prostate.

When rats were injected with the progestin ethynodiol diacetate in doses that suppressed spermatogenesis and the growth of accessory sex glands, the level of phosphodiesterase in epididymal and prostate tissues increased 5- to 10-fold. This increase was prevented by concurrent administration of testosterone propionate. A similar increase in phosphodiesterase activity was observed in the epididymides and prostates of castrated animals, with reversal by treatment with androgen. In immature rats approaching puberty, the phosphodiesterase activity in epididymis and prostate increased while the blood testosterone level remained low; as the testosterone level rose with the onset of puberty, the phosphodiesterase activity decreased. Incubation of enzymically active extracts of accessory tissues from castrated rats with heat-treated extracts of the corresponding normal tissues resulted in strong inhibition of the initially high phosphodiesterase activity. The addition of heat-treated extracts of accessory glands from castrated rats to enzymically active extracts of the corresponding tissues from normal rats resulted in a marked elevation of their phosphodiesterase activities. Of the two heat-stable modulators, the inhibitor factor was dialyzable. The dependence of this factor on testosterone suggests a mechanism of action by which the steroid hormone, by inducing the production in its target tissues of an inhibitory modulator of phosphodiesterase, controls the maintenance of functional levels of cAMP.