Feeding responses to mu-, delta- and kappa-opioid receptor agonists in the meat-type chick

The present study was designed to examine the effect of specific opioid agonists on feeding behavior in neonatal chicks. The food intake of broiler chicks was significantly decreased by intracerebroventricular injection of DAMGO and beta-casomorphin, micro-opioid receptor agonists, at 30-min postinjection. In contrast, both delta-opioid receptor agonists (DADLE and DPDPE) stimulated the food intake of the chick. Similar to the delta-opioid receptor agonists, food intake was elevated by the kappa-opioid receptor agonist (U-50488H and U-62066) in a dose-dependent manner. These results suggest that the endogenous opioid peptides have an important role for feeding behavior in the central nervous system of chicks.     

Scrotal disorders: evaluation of testicular enhancement patterns at dynamic contrast-enhanced subtraction MR imaging

PURPOSE: To evaluate testicular enhancement patterns in various scrotal disorders at dynamic contrast medium-enhanced subtraction magnetic resonance (MR) imaging. MATERIALS AND METHODS: Forty-two patients with scrotal symptoms (22 testicular diseases, 20 extratesticular scrotal disorders) underwent three-dimensional (3D) fast field-echo or fast spin-echo dynamic subtraction MR imaging after injection of paramagnetic contrast medium. The relative percentages of peak height and mean slope of the testes on the affected side were compared with those on the unaffected side by using time-signal intensity curves. RESULTS: Extratesticular scrotal disorders (time-signal intensity curve mean peak height, 93.1%; mean slope, 89.8%) showed gradual and progressive increase in homogeneous testicular contrast enhancement in all normal testes. Relative percentages of peak height and mean slope of testicular torsion (mean peak height, 17.3%; mean slope, 10.6%), infarction (mean peak height, 30.4%; mean slope, 19.8%), traumatic hemorrhagic necrosis (mean peak height, -3.5%; mean slope, -12.0%), and epidermoid cyst (mean peak height, -6.6%; mean slope, -14.2%) were significantly lower than those of extratesticular scrotal disorders. Acute mumps orchitis (mean peak height, 135.1%; mean slope, 307.5%) and malignant testicular tumor (mean peak height, 178.7%; mean slope, 467.6%) showed higher relative percentages of peak height and mean slope. CONCLUSION: Dynamic contrast-enhanced subtraction MR imaging can provide information about testicular perfusion on the basis of contrast enhancement and can be used to differentiate testicular diseases from scrotal disorders.     

Isavuconazole for treatment of rare invasive fungal diseases

Data regarding treatment of rare invasive fungal diseases (IFDs) are scarce. We documented the efficacy and safety of isavuconazole for treatment of uncommonly diagnosed IFDs. VITAL was a single‐arm, international, open‐label study evaluating the efficacy and safety of isavuconazole (200 mg orally or intravenously every 8 hours for 48 hours, then once daily). The primary outcome was overall response at Day 42; key secondary outcomes were overall responses at Day 84 and end of treatment (EOT), mortality at Days 42 and 84, and safety. This analysis includes patients with IFD caused by rare or unidentified pathogens. Twenty‐six patients with IFDs caused by rare moulds (n = 17), non‐Candida yeasts (n = 2), or unidentified moulds (n = 7) were enrolled (median treatment duration [range], 114.5 [1‐496]) days. Overall treatment success was observed in 11/26 (42.3%), 10/26 (38.5%), and 15/26 (57.7%) patients at Days 42, 84, and EOT, respectively. All‐cause mortality rates were 2/26 patients (7.7%) at Day 42 and 4/26 patients (15.4%) at Day 84; another two patients died after Day 84. All patients had ≥1 treatment‐emergent adverse event (TEAE); 15 patients (57.7%) had serious TEAEs, and TEAEs led to discontinuation of isavuconazole in four patients (15.4%). Isavuconazole may be efficacious for treatment of a range of rare IFDs.     

Bilan de la première année d'activité de « APAAC Infos Services »

ContextIn Ivory Coast, the APAAC association “Let us help persons living with cancer or affected by cancer”, in French “Aidons les Personnes Atteintes ou Affectées par le Cancer” (APAAC), set up the first ivorian call center to support persons living with or affected by cancer and to inform population about cancer.Purposes of the studyTo show the feasibility of such a service in a developing country and to present the first results.MethodologyThis helpline is, since January 28th, 2010, directly accessible to the population by a fixed phone number. The population can, with a local cost call, contact a specialists team (psychologist, adviser in help relation or doctor), in total confidentiality, every Thursday from 3 pm till 5 pm. OutsideThursdays, informations about cancer are available on vocal server 24 hours a day and seven days a week. Callers are welcomed by a message inviting them either to listen to a recorded message about cancer or about APAAC association or finally to speak to a specialist online. Retrospective study based on the statistics of the call center. Because of a problem arisen on the statistics software, our results carry only over the period from August to December, 2010.ResultsWe had, during this period, 462 calls among which 23 in August, 58 in September, 67 in October, 230 in November and 84 in December. Reasons of the increasing of the figures are justify by the poster campaign in September and the communication around the service on television program in November. On these 462 calls, we had 35 real communications among whom 10 calls interrupted. The reason was the lack of call credit. The average of the call time was of 20 minutes for the conversations with the specialists. Three hundred and forty-three persons stopped to the welcome message, 341 (9%) listen information on the cancer, 27 (6%) listen information about the association. Sixteen persons wished to speak to specialists but were not regrettably able to make it because having called up except the hours of presence. Three hundred and fifty-five calls took place the working days. The most sought time slots were the ones of 7 am to 6 pm.ConclusionThose results raises questions about the necessity to create and to continue this kind of telephone counseling for cancer, but also on the need of communication and extension of listening days and hours. In our country context with a population with weak resources, the necessity of access to free call was also raised.     

Isavuconazole for treatment of invasive fungal diseases caused by more than one fungal species

The optimal approach to treat invasive fungal disease (IFD) caused by more than one fungal species is unknown. We documented the efficacy and safety of isavuconazole for treatment of IFDs caused by more than one fungal species. VITAL was a single‐arm, international, open‐label study evaluating the efficacy and safety of isavuconazole (200 mg orally or intravenously every 8 hours for 48 hours, then once daily) for treatment of rare IFDs. The primary outcome was the overall response at Day 42; key secondary outcomes were overall responses at Day 84 and end of treatment (EOT), mortality at Days 42 and 84, and safety. This analysis includes patients with IFD caused by multiple fungal species. Fifteen patients were included in this analysis (including Aspergillus spp., n = 11; without Aspergillus spp., n = 4); median treatment duration was 97 days [range, 6‐544] days). Overall treatment success was observed in 2/15 patients (13.3%) at Days 42 and 84, and 2/14 (14.3%) at EOT. All‐cause mortality was 2/15 (13.3%) at Day 42 and 4/15 (26.7%) at Day 84. All patients had ≥1 treatment‐emergent adverse event (TEAE); 12 patients (80.0%) had serious TEAEs; TEAEs led to discontinuation of isavuconazole in two patients (13.3%). Isavuconazole may be useful to treat some IFDs caused by multiple fungal species.     

High intensity areas on noncontrast T1-weighted MR images in cerebral infarction

Among 46 noncontrast magnetic resonance studies on patients with cerebral infarction, 11 showed areas of high signal intensity of the involved brain on T1-weighted images. These areas were more frequent in cerebral or cerebellar cortical lesions. Lacunar infarcts in lenticular nuclei, internal capsules, corona radiata, or brain stem did not show any high signal intensity areas on T1-weighted images, whereas the thalamic infarcts did. Sequential studies revealed that these lesions displayed low signal intensity on T2-weighted images at first, and then a high signal intensity area appeared on T1-weighted images. We suggest that these high signal intensity areas on the T1-weighted images in cerebral infarction are caused by hemorrhagic changes at the periphery of the infarction, where blood flow is restored by recanalization or collateral supply.     

Sphingomyelin distribution in lipid rafts of artificial monolayer membranes visualized by Raman microscopy

Sphingomyelin (SM) and cholesterol (chol)-rich domains in cell membranes, called lipid rafts, are thought to have important biological functions related to membrane signaling and protein trafficking. To visualize the distribution of SM in lipid rafts by means of Raman microscopy, we designed and synthesized an SM analog tagged with a Raman-active diyne moiety (diyne-SM). Diyne-SM showed a strong peak in a Raman silent region that is free of interference from intrinsic vibrational modes of lipids and did not appear to alter the properties of SM-containing monolayers. Therefore, we used Raman microscopy to directly visualize the distribution of diyne-SM in raft-mimicking domains formed in SM/dioleoylphosphatidylcholine/chol ternary monolayers. Raman images visualized a heterogeneous distribution of diyne-SM, which showed marked variation, even within a single ordered domain. Specifically, diyne-SM was enriched in the central area of raft domains compared with the peripheral area. These results seem incompatible with the generally accepted raft model, in which the raft and nonraft phases show a clear biphasic separation. One of the possible reasons is that gradual changes of SM concentration occur between SM-rich and -poor regions to minimize hydrophobic mismatch. We believe that our technique of hyperspectral Raman imaging of a single lipid monolayer opens the door to quantitative analysis of lipid membranes by providing both chemical information and spatial distribution with high (diffraction-limited) spatial resolution.Specific membrane microdomains, called lipid rafts, are thought to have important biological functions in cells (1, 2). The rafts are frequently defined as detergent-resistant membrane domains and enriched in sphingomyelin (SM) and cholesterol (chol). Certain membrane proteins, such as glycosylphosphatidylinositol-anchored proteins and acylated cytosolic proteins, are considered to show preferential association with those raft lipids, which thereby, facilitate various biological functions, including membrane trafficking and signal transduction (3). Therefore, an understanding of the distribution of SMs within lipid rafts is expected to provide basic information about site-specific cellular functions.The basic features of lipid rafts have often been examined using SM/phosphatidylcholine (PC)/chol mixtures as model membrane systems, because these ternary mixtures undergo phase separation into raft-like ordered domains and fluid disordered domains (4). In addition, the membrane properties of these ordered domains, such as detergent insolubility, are similar to those of lipid rafts in biomembranes (5). However, there are few reports on the lipid distribution in the raft mixtures, because detergent extraction provokes reorganization of the lipids and consequently, obscures information about the inherent domains (6). Thus, direct observation is essential to investigate the lipid distribution in intact lipid preparations.Fluorescence microscopy has been widely used to observe phase separation in lipid membranes (7), and fluorescently labeled lipids or lipophilic dyes have generally been used as imaging agents (8). However, these fluorescent lipids are frequently excluded from the raft-like ordered domains, probably because the large fluorophores perturb the lipid packing (8, 9). So far, there is no lipid probe that can directly visualize the distribution of intrinsic SM molecules in multicomponent membranes, although some peptide-based large probes that recognize raft domains have been developed (10, 11). Consequently, direct observation of SM distribution in lipid rafts has not proved feasible with fluorescence-based imaging modalities.Here, we focused on spontaneous Raman scattering microscopy to directly and chemoselectively visualize the distribution of a lipid constituent in lipid rafts using a ternary lipid monolayer system as a model. Raman spectroscopy has chemical specificity, because it detects characteristic molecular vibration frequencies. The molecular distribution in a sample can be determined by Raman microscopy, and the image has quantitative chemical contrast, because the scattering intensity is proportional to the number of molecules in the detection volume. A molecule-specific full spectrum is obtained for each pixel, allowing us to analyze the molecular composition and state of the lipid mixture at each position, with the help of accumulated knowledge on Raman spectra of lipid membranes obtained over the last few decades (12). Because Raman microscopy uses an optical detection scheme, minimally invasive noncontact observation of a sample can be achieved under atmospheric pressure.Despite these advantages, spontaneous Raman microscopy has not yet been used for imaging of lipid rafts to our knowledge. It is partly because Raman imaging of a single lipid membrane has long been thought to be infeasible from a sensitivity point of view owing to the extremely weak scattering signal from the limited number of lipid molecules in the detection volume (13). Spatial resolution is also restricted by the imaging time, because a weak scattering signal tends to require a long exposure time, resulting in limited pixel numbers for imaging within a realistic observation time. However, recent developments in spontaneous Raman microscopy have allowed us to overcome this problem; efficient optical systems and a parallel Raman excitation/detection configuration (14–16) improve imaging speed with both high sensitivity and high diffraction-limited spatial resolution.As a target lipid component for observation by Raman microscopy in a raft-containing membrane, we focused on SM, and newly synthesized an SM analog with a Raman-active alkyne moiety. Alkyne is a promising tag in terms of both its small chemical structure and its high Raman scattering intensity in the silent region of biomolecules, allowing selective detection of alkyne-tagged molecules (17, 18). We first attempted Raman imaging using a propargyl-SM analog with a single alkyne group, but the intensity was insufficient for imaging. Because a conjugated diyne group shows a stronger Raman band (18), we next aimed to introduce a 6-hydroxy-hexa-2,4-diynyl group at the ammonium moiety of the head group; the 6-hydroxyl group was expected to increase the hydrophilicity of this relatively hydrophobic Raman tag (Fig. 1). We found that diyne-SM was effective for spontaneous Raman imaging of SM in a raft-mimicking ternary monolayer system.Open in a separate windowFig. 1.Chemical structures of SM, diyne-SM, DOPC, and chol.     

Roles of kidney and submandibular gland in the release of rat plasma inactive renin

In this study we outlined the development of an enzymatic technique to activate plasma inactive renin by trypsin in rat plasma. Using this method, we reported the releasing mechanism of the trypsin-activable inactive renin which has not yet been clarified. Adult male Wistar rats (260-300 g) were kept on regular diet (Na: 260 mg/100g) unless explained and underwent operation under pentobarbital anesthesia (50 mg/kg). Blood samples were obtained from conscious rats through the cannulae, which had been inserted into the left femoral arteries 24h before the experiments. After addition of excessive renin substrate which had been obtained from the 24 h-nephrectomized rat plasma, renin was measured by the commercial RIA-kit (Dainabot). Trypsin (Worthington) treatment (20 mg/ml plasma for 10 min at 4 degrees C) was followed by addition of SBTI (Sigma) (20 mg/ml plasma). This condition maximally increased the rate of angiotensin I generation and did not alter the Km or optimum pH of the renin reaction. In this condition, trypsin reaction was completely inhibited by adding these concentrations of SBTI. The molecular weight of inactive renin (51,000) in the normal rat plasma estimated by Sephadex G-100 column (Pharmacia) was the same as that in the nephrectomized rat plasma. In conclusion, trypsin treatment of plasma (20 mg/ml plasma for 10 min at 4 degrees C) followed by SBTI (20 mg/ml plasma) was justified for trypsin activation of rat plasma. Using this method, we investigated the changes in active and inactive renin after bilateral nephrectomy in the salt-depleted rat. Active renin decreased rapidly after bilateral nephrectomy with a half life of 23.6 +/- 4.0 min. Inactive renin, on the other hand, increased gradually and reached to a plateau 24 h after bilateral nephrectomy, and was kept unchanged during the following 24 h. The infusion of mouse submandibular gland active renin or angiotensin II could not prevent the increase of plasma inactive renin in the nephrectomized rat. These suggest that there may be no feedback mechanisms between plasma inactive and active renin or angiotensin II. Furthermore, we investigated the organ-related sources of plasma inactive renin which markedly increased after total nephrectomy. Simultaneous removals of submandibular glands but not of adrenal glands completely prevented the postnephrectomy increases of plasma inactive renin. But, removals of submandibular glands or adrenal glands alone were followed by no changes in the basal levels of plasma inactive renin.(ABSTRACT TRUNCATED AT 400 WORDS)     

MR imaging of testicular torsion: features of testicular hemorrhagic necrosis and clinical outcomes

PURPOSE: To determine whether emergency subtraction dynamic contrast-enhanced MR imaging (DCE-MRI) in combination with T2- and T2*-weighted imaging of the testis is useful in the evaluation of patients with testicular torsion. MATERIALS AND METHODS: Fourteen patients with surgically proven testicular torsion were examined using preoperative emergency MRI, including T2-weighted, T2*-weighted, and DCE-MRI. The affected testis was examined histologically in eight patients who underwent orchiectomy, and by postoperative follow-up MRI in six patients who underwent orchiopexy. The diagnostic criteria for testicular torsion and detection of hemorrhagic necrosis in the affected testis in emergency MRI were decreased or no perfusion in DCE-MRI and a spotty and/or streaky pattern of low or very low signal intensity in T2- and T2*-weighted images. The intraoperative findings and clinical outcomes were also compared. RESULTS: The histological findings and follow-up MR images revealed total or partial necrosis of the affected testis in 10 of the 14 patients. In the diagnosis of complete torsion, the sensitivities were 100% for DCE-MRI and 75% for T2- and T2*-weighted imaging. In the detection of testicular necrosis, T2- and T2*-weighted imaging showed the highest accuracy (100%), followed by 12-hour time from onset (93%), intraoperative findings (79%), and DCE-MRI (71%). CONCLUSION: Emergency MRI can help diagnose testicular torsion and detect testicular necrosis when DCE-MRI is used in combination with T2- and T2*-weighted images.