Evidence for a feeding related association between melanocortin in the NTS and Neuropeptide-Y in the PVN.

Melanocortin and neuropeptide-Y (NPY) are both involved in feeding and energy regulation, and they have opposite effects in the paraventricular nucleus of the hypothalamus (PVN). The present study examined an interaction between melanocortin in the nucleus of the solitary tract (NTS) and NPY in the PVN. Male Sprague-Dawley rats were implanted with cannulae in the injection sites of interest. In Experiment 1, subjects received either the melanocortin 3/4-receptor (MC3/4) antagonist SHU9119 (0, 10, 50 and 100 pmol/0.5 µl) or the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 µl) into the NTS. Food intake was measured at 1, 2, 4, 6 and 24-h post-injection. Administration of SHU9119 into the NTS significantly and dose-dependently increased food intake at 1, 2, 4, 6 and 6-24-h, and administration of MTII into the NTS significantly and dose-dependently decreased 24-h free feeding. In Experiment 2, subjects received the MC3/4 agonist MTII (0, 10, 50, 100 and 200 pmol/0.5 µl) into the NTS just prior to NPY (0 and 1µg/0.5 µl) in the PVN. PVN injection of NPY stimulated feeding, and administration of MTII (50, 100 and 200 pmol) into the NTS significantly and dose-dependently decreased NPY-induced feeding at 2, 4, 6 and 6-24-h. These data suggest that there could be a neuronal association between melanocortin in the NTS and NPY in the PVN, and that the melanocortin system in the NTS has an antagonistic effect on NPY-induced feeding in the PVN.

Long-term low-dose macrolides for chronic rhinosinusitis in adults - a systematic review of the literature.

BACKGROUND: Chronic rhinosinusitis is a very common inflammatory disease that impairs quality of life and is associated with high healthcare spending. Chronic rhinosinusitis treatment commonly involves the use of intranasal corticosteroids, oral antibiotics, and surgery. Macrolides have been identified as a potential treatment option for chronic rhinosinusitis due to their immunomodulatory effects; however, the evidence supporting their use is still conflicting. OBJECTIVE: The purpose of this systematic review was to evaluate new evidence along with previously reported studies of the use of macrolides in the treatment of chronic rhinosinusitis. SEARCH STRATEGY: Medline, EMBASE, Cochrane CENTRAL, LILACS, clinicaltrials.gov, and the International Clinical Trials Registry Platform were all searched (until June 2015 Medline and EMBASE searches were updated January 2016). Randomised controlled trials comparing low-dose macrolide antibiotics versus placebo, as an adjunct to other therapies, or low-dose macrolide therapy alone versus other therapies were included in this review. EVALUATION METHOD: Quality of the evidence was evaluated using the Cochrane risk of bias tool. Continuous outcomes were expressed as mean differences or standardised mean differences with 95% confidence interval. Data were pooled using fixed-effects models. RESULTS: Nine randomised controlled trials met the inclusion criteria. Studies were classified into three distinct comparisons: Low-dose macrolide therapy vs. placebo, low-dose macrolide +/- nasal steroids vs. nasal steroid and low-dose macrolides vs. other therapies. The overall quality of the evidence is low due to limitations in study design, imprecision, and indirectness. CONCLUSIONS: Positive results were seen with the use of macrolide therapy in the postoperative period in patients with nasal polyps. A firm conclusion with respect to the effectiveness of the use of macrolides for the treatment of chronic rhinosinusitis cannot be reached based on the available evidence. Further study using a placebo-controlled design evaluating the use of macrolides in clearly defined chronic rhinosinusitis populations is needed.

Blood: tests used to assess the physiological and immunological properties of blood.

The properties of blood and the relative ease of access to which it can be retrieved make it an ideal source to gauge different aspects of homeostasis within an individual, form an accurate diagnosis, and formulate an appropriate treatment regime. Tests used to determine blood parameters such as the erythrocyte sedimentation rate, hemoglobin concentration, hematocrit, bleeding and clotting times, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean cell volume, and determination of blood groups are routinely used clinically, and deviations outside the normal range can indicate a range of conditions such as anemia, pregnancy, dehydration, overhydration, infectious disease, cancer, thyroid disease, and autoimmune conditions, to mention a few. As these tests can be performed relatively inexpensively and do not require high levels of technical expertise, they are ideally suited for use in the teaching laboratory, enabling undergraduate students to link theory to practice. The practicals described here permit students to examine their own blood and that of their peers and compare these with clinically accepted normal ranges. At the end of the practicals, students are required to answer a number of questions about their findings and to link abnormal values to possible pathological conditions by answering a series of questions based on their findings.

Enrichment of heavy metals and organic compounds in the surface microlayer of Narragansett Bay, Rhode Island.

Concentrations of lead, iron, nickel, copper, fatty acids, hydrocarbons, and chlorinated hydrocarbons are enriched from 1.5 to 50 times in the top 100 to 150 micrometers of Narragansett Bay water relative to the bulk water 20 centimeters below the surface. Trace metal enrichment was observed in the particulate and organic fractions but not in the inorganic fraction. If these substances are concentrated in films only a few molecular layers thick on the water surface, the actual enrichment factor in the films may be well over 10(4), resulting in extremely high localized pollutant concentrations in the surface microlayer.

Effect of reserpine on the generation of the chromogranin A-derived neuropeptide WE-14 in rat oxyntic mucosa.

WE-14, a post-translational product of the neuroendocrine protein chromogranin A (CgA), is generated in distinct subpopulations of endocrine cells. The objective of this study was to investigate the generation of WE-14 in the endocrine cell types of the oxyntic mucosa of the stomach, after treatment with reserpine, an irreversible inhibitor of vesicular monoamine uptake 2 (VMAT2). Reserpine (10 mg/kg) was administered subcutaneously and tissue analysed 1, 3, 5 and 18 h following treatment. The oxyntic mucosa was analysed immunohistochemically employing a site-specific WE-14 antiserum, a region-specific CgA antiserum and an antiserum against histidine decarboxylase (HDC), a marker of the histamine-producing ECL cells in the oxyntic mucosa. The number of oxyntic endocrine cells exhibiting WE-14 immunostaining increased more than 100-fold 18 h after reserpine administration relative to vehicle treated controls. Double immunostaining with HDC revealed that most, but not all, of the WE-14 positive cells were ECL cells. These results suggest that reserpine has the ability to influence the post-translational processing of CgA to generate WE-14 in rat stomach ECL cells, presumably as a consequence of reduced VMAT2-driven accumulation of histamine.

Detection of blood group antigens utilising immobilised antibodies and surface plasmon resonance.

Surface plasmon resonance (SPR) detection using the BIAcore biosensing system was employed for the detection of blood group-associated antigens (BGAA) on whole erythrocytes. The quantitative detection of erythrocytes was accomplished by covalently immobilising blood group-specific antibodies (IgM) to a dextran matrix and monitoring the cell binding response. Non-specific binding of erythrocytes to the IgM coated surface was not detected. Relatively mild regeneration conditions (20 mM NaOH) were employed to elute bound erythrocytes in order to preserve the activity of the immobilised antibody and allow the surface to be used repeatedly. Regeneration of the surface was particularly difficult when a high IgM immobilisation level was used and when the number of bound cells was high. Despite these considerations, a quantitative relationship between the cell binding response and erythrocyte concentration was confirmed. Erythrocyte preparations, diluted by a factor of ten as compared to physiological concentrations, were detectable. The occurrence of non-specific false positives appears to be minimal and allows the system to be used for blood typing. As a model study, the lectin concanavalin A (ConA) was covalently immobilised onto a hydrophilic dextran matrix and successfully used to support the capture of erythrocytes from suspension.

WE-14, a chromogranin a-derived neuropeptide.

The neuropeptide WE-14 is derived from the posttranslational processing of chromogranin A (CgA). While CgA is expressed in a preponderance of neuroendocrine cells, WE-14 is generated in a distinct subpopulation of CgA-immunopositive cells, most notably in the adrenal, pituitary, and parathyroid glands. Physiological and pharmacological studies have demonstrated that CgA is cleaved to generate WE-14 in the adrenal chromaffin cell population and in the enterochromaffin-like (ECL) cells of the oxyntic mucosa. Pathological analyses of neuroendocrine tumors have revealed a heterogeneous pattern of WE-14 immunostaining, with variable concentrations quantified and chromatographically resolved in tissue extracts. Phylogenetic surveys have demonstrated that WE-14 exhibits an ancient lineage, while ontogenetic examination has shown that it is generated at an early stage during fetal development. Putative WE-14 receptor binding sites have been identified in several tissues; however, the physiological role of WE-14 remains enigmatic.

The purification and specificity of a lipase fromVernonia anthelmintica seed.

Acetone powders prepared fromVernonia anthelmintica seed catalyzed the release of 6.4 to 9.6 mu-moles of free fatty acids per milligram of protein when blended with olive oil and phosphate buffer and shaken for 20 min at 43 C. A 20 fold purification was achieved by differential centrifugation of an ammonium hydroxide extract of the acetone powder. Results from Sephadex G-200 chromatography and polyacrylamide gel electrophoresis suggested that the lipase activity was associated with a molecule of molecular weight greater than 200,000. Free fatty acids, 1,2- and 1,3-diglycerides, monoglycerides and glycerol were found in the digestion products. With most substrates the 1,2-to 1,3-diglyceride ratio was approximately 2ratio1 and monoglycerides tended to accumulate. Analysis of the digestion products from synthetic triglycerides of known structure indicated that both primary and secondary ester positions of the triglyceride molecule were hydrolyzed and that considerable isomerization of 1,2-diglyceride to 1,3-diglyceride occurred. The monoglyceride was consistently lower than the 1,2-diglyceride and in the majority of cases also lower than the 1,3-diglyceride in the fatty acid originally present in the 2 position of the triglyceride. No fatty acid preference was observed.

Studies on the specificity of a lipase system fromGeotrichum candidum.

The lipase system fromGeotrichum candidum preferentially hydrolyzed oleic acid, regardless of position, from the four possible racemic triglycerides containing oleate and palmitate. The rate of hydrolysis of these glycerides was most rapid when the substrate contained two moles of oleate. This acid was also preferentially released from a series of triglycerides containing oleate and two moles of a saturated fatty acid. The chain length of the latter did not alter the specificity for oleate.Equimolar quantities of oleic and linoleic acids were released when triolein and trilinolein (equimolar mixture) were hydrolyzed by this lipase. No differentiation between oleate and palmitoleate was observed when racemic glyceryl 1-palmitoleate-2,3-dioleate was the substrate. However, only 7.2 M%cis-vaccenic acid was released from glyceryl 1-cis-vaccenate-2,3-dioleate and 5.4 M% petroselinic acid from glyceryl 1-palmitoleate-2,3-dipetroselinate. It therefore appears that the enzyme may be specific forcis-9-unsaturation as well as forcis-9,cis-12-unsaturation. When specificity was assumed, the fatty acid compositions of the diglycerides obtained from digestions withG. candidum were close to theoretical.

Digestion of butyrate glycerides by pancreatic lipase.

The racemic triglycerides, glyceryl-1-palmitate-2,3-dibutyrate (PBB), glyceryl-1-butyrate-2,3-dipalmitate (PPB), glyceryl-2-butyrate-1,3-dipalmitate (PBP), and the diglyceride, racemic glyceryl-1-palmitate-3-butyrate (P-B) were synthesized and digested with pancreatic lipase. Each triglyceride was mixed with equimolar amounts of triolein (OOO) prior to incubation.The following order of digestion rates was observed: PBB>PPB>PBP>P-B. There was no evidence for short-chain fatty acid specificity; however the triglycerides containing butyric acid were hydrolyzed more rapidly than OOO. Based upon the fatty acid composition of partial glycerides, digestion of butyrate glycerides was not a simple phenomenon. For example, in the digestion of PBB, butyric acid accumulated faster than palmitic acid in the diglycerides, and monobutyrin was found to accumulate when the diglyceride, P-B, was digested. As evidenced by the fatty acid composition of the monoglycerides, positional specificity of pancreatic lipase was always maintained.

Accumulation of polycyclic aromatic hydrocarbons in crankcase oil.

The concentrations of polycyclic aromatic hydrocarbons (PAHs) were measured in automotive crankcase oils. PAHs were not detected in the new oil; however, concentrations increased rapidly with usage in the gasoline engine of an automobile. The PAH distributions found were dominated by alkylated two- and three-ring compounds. The concentrations of these compounds increased until about 4000 miles and then levelled out. Four-ring compounds continually increased with miles driven, and the five-ring benzopyrenes were only detected in the oil used for the longest distance (about 5800 miles).

Relationships among total lipid, lipid classes, and polychlorinated biphenyl concentrations in two indigenous populations of ribbed mussels (Geukensia demissa) over an annual cycle.

Two indigenous ribbed mussel (Geukensia demissa) populations were sampled approximately every four weeks during 1997 to investigate the relationships among concentrations of total lipid, lipid classes, and polychlorinated biphenyls (PCBs). One population was located in a highly contaminated area near a Superfund site (New Bedford Harbor, MA, USA), while the other population was located at a relatively clean site (West Island, Fairhaven, MA, USA). Mussel tissue total PCB concentrations (quantified as the sum of 18 congeners) from the contaminated site were two orders of magnitude greater than those at the clean site. Total lipid and triacylglycerol (TG) also were higher at the contaminated site. No significant relationship (p > 0.05) was observed between total PCBs and total lipid at either location; however, the correlations at both sites increased when total PCBs were compared with total TG or, to a lesser extent, total nonpolar lipid. Principal component analysis and linear discriminatory analysis indicated that the two mussel populations could be distinguished by the proportions of their lipid classes, particularly the concentration of nonpolar lipids, which consisted mainly of TG. These results suggest that the standard method of normalizing organism PCB concentrations to total lipid may not be appropriate as a routine practice, especially when the organism has a relatively low total lipid content (<6% dry wt in this study).

The North Cape oil spill: hydrocarbons in Rhode Island coastal waters and Point Judith Pond.

On 19 January 1996, the North Cape oil barge ran aground near Moonstone Beach, RI, and spilled over 2700 metric tons of No. 2 fuel oil during a severe winter storm. High winds and rough seas drove the oil into the water column, and the oil spread throughout Block Island Sound and into several coastal salt ponds. Over 50 water samples were collected from Point Judith Pond (PJP) and the southern coast of Rhode Island for four months after the spill and analyzed for polycyclic aromatic hydrocarbons (PAHs) and total petroleum hydrocarbons (TPHs). These analyses revealed that at least 60 km2 of coastal waters were impacted from the spill. Maximum concentrations of sigmaPAHs and TPHs were 115 and 3940 microg l(-1), respectively. The percentage of sigmaPAHs relative to the TPHs for all samples varied from 0.2 to 43%, showing that there was no clear relationship between sigmaPAHs and TPHs for the whole dataset and likely resulting from spatial and temporal partitioning over the course of the spill. However, within the dataset, there were stronger correlations for distinct samples collected at similar locations and times. In PJP, water column concentrations of individual PAHs decreased at rates of 0.08-0.24 day(-1) and lower-molecular weight PAHs were removed faster than higher-molecular weight PAHs.

A Critical Evaluation of Interlaboratory Data on Total, Elemental, and Isotopic Carbon in the Carbonaceous Particle Reference Material, NIST SRM 1649a.

Because of increased interest in the marine and atmospheric sciences in elemental carbon (EC), or black carbon (BC) or soot carbon (SC), and because of the difficulties in analyzing or even defining this pervasive component of particulate carbon, it has become quite important to have appropriate reference materials for intercomparison and quality control. The NIST "urban dust" Standard Reference Material(®) SRM 1649a is useful in this respect, in part because it comprises a considerable array of inorganic and organic species, and because it exhibits a large degree of ((14)C) isotopic heterogeneity, with biomass carbon source contributions ranging from about 2 % (essentially fossil aliphatic fraction) to about 32 % (polar fraction). A primary purpose of this report is to provide documentation for the new isotopic and chemical particulate carbon data for the most recent (31 Jan. 2001) SRM 1649a Certificate of Analysis. Supporting this is a critical review of underlying international intercomparison data and methodologies, provided by 18 teams of analytical experts from 11 institutions. Key results of the intercomparison are: (1) a new, Certified Value for total carbon (TC) in SRM 1649a; (2) (14)C Reference Values for total carbon and a number of organic species, including for the first time 8 individual PAHs; and (3) elemental carbon (EC) Information Values derived from 13 analytical methods applied to this component. Results for elemental carbon, which comprised a special focus of the intercomparison, were quite diverse, reflecting the confounding of methodological-matrix artifacts, and methods that tended to probe more or less refractory regions of this universal, but ill-defined product of incomplete combustion. Availability of both chemical and (14)C speciation data for SRM 1649a holds great promise for improved analytical insight through comparative analysis (e.g., fossil/biomass partition in EC compared to PAH), and through application of the principle of isotopic mass balance.

mRNA levels of BACE1 and its interacting proteins, RTN3 and PPIL2, correlate in human post mortem brain tissue.

ß-Site amyloid precursor protein cleaving enzyme (BACE1) is the rate-limiting enzyme for production of Aß peptides, proposed to drive the pathological changes found in Alzheimer's disease (AD). Reticulon 3 (RTN3) is a negative modulator of BACE1 (ß-secretase) proteolytic activity, while peptidylprolyl isomerase (cyclophilin)-like 2 (PPIL2) positively regulated BACE1 gene expression in a cell-based assay. This study aimed to analyze RTN3 and PPIL2 mRNA levels in four brain regions from individuals with AD and controls. BACE1 mRNA had been previously quantified in the samples, as had glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE), to track changing cell populations in the tissue. mRNA levels in the human post mortem brain tissue were assayed using quantitative real-time polymerase chain reaction (qPCR) and qbase(PLUS), employing validated stably expressed reference genes. No differences in RTN3 or PPIL2 mRNA levels were found in individuals with AD, compared to controls. Both RTN3 and PPIL2 mRNA levels correlated significantly with BACE1 mRNA and all three showed similar disease stage-dependent changes with respect to NSE and GFAP. These findings indicated that the in vitro data demonstrating an effect of PPIL2 on BACE1 expression have functional relevance in vivo. Further research into BACE1-interacting proteins could provide a fruitful approach to the modulation of this protease and consequently Aß production.