Calcium and other signalling pathways in neuroendocrine regulation of somatotroph functions

Relative to mammals, the neuroendocrine control of pituitary growth hormone (GH) secretion and synthesis in teleost fish involves numerous stimulatory and inhibitory regulators, many of which are delivered to the somatotrophs via direct innervation. Among teleosts, how multifactorial regulation of somatotroph functions are mediated at the level of post-receptor signalling is best characterized in goldfish. Supplemented with recent findings, this review focuses on the known intracellular signal transduction mechanisms mediating the ligand- and function-specific actions in multifactorial control of GH release and synthesis, as well as basal GH secretion, in goldfish somatotrophs. These include membrane voltage-sensitive ion channels, Na(+)/H(+) antiport, Ca(2+) signalling, multiple pharmacologically distinct intracellular Ca(2+) stores, cAMP/PKA, PKC, nitric oxide, cGMP, MEK/ERK and PI3K. Signalling pathways mediating the major neuroendocrine regulators of mammalian somatotrophs, as well as those in other major teleost study model systems are also briefly highlighted. Interestingly, unlike mammals, spontaneous action potential firings are not observed in goldfish somatotrophs in culture. Furthermore, three goldfish brain somatostatin forms directly affect pituitary GH secretion via ligand-specific actions on membrane ion channels and intracellular Ca(2+) levels, as well as exert isoform-specific action on basal and stimulated GH mRNA expression, suggesting the importance of somatostatins other than somatostatin-14.     

Immunohistochemical study on the ontogenetic development of the regional distribution of peptide YY, pancreatic polypeptide, and glucagon-like peptide 1 endocrine cells in bovine gastrointestinal tract

The regional distribution and relative frequency of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and glucagon-like peptide 1 (GLP-1)-immunoreactive (IR) cells were determined immunohistochemically in the gastrointestinal tract at seven ontogenetic stages in pre- and postnatal cattle. Different frequencies of PYY-, PP-, and GLP-1-IR cells were found in the intestines at all stages; they were not found in the esophagus and stomach. The frequencies varied depending on the intestinal segment and the developmental stage. The frequencies of PYY- and PP-IR cells were lower in the small intestine and increased from ileum to rectum, whereas GLP-1-IR cells were more numerous in duodenum and jejunum, decreased in ileum and cecum, and increased again in colon and rectum. The frequencies also varied according to pre- and postnatal stages. All three cell types were most numerous in fetus, and decreased in calf and adult groups, indicating that the frequencies of these three types of endocrine cells decrease with postnatal development. The results suggest that these changes vary depending on feeding habits and adaptation of growth, secretion, and motility of intestine at different ontogenetic stages of cattle.     

Oxytocin protects cardiomyocytes from apoptosis induced by ischemia-reperfusion in rat heart: role of mitochondrial ATP-dependent potassium channel and permeability transition pore

The current study examines the protective effect of oxytocin (OT) on cardiomyocyte apoptosis modulated by mitochondrial ATP-dependent potassium (mitoKATP) channel and permeability transition pore (mPTP) in the preconditioned myocardium of anesthetized rats. Eighty rats were equally divided into eight groups. The hearts of all animals except for the sham group were subjected to 25 min ischemia and 120 min reperfusion. Oxytocin, 5-hydroxydeconoate (5-HD), a specific inhibitor of the mitoKATP channel, and atractyloside (ATRC), an mPTP opener, were used prior to ischemia. Hemodynamic parameters were recorded throughout the experiment. Evaluations were made by infarct size, plasma lactate dehydrogenase level (LDH), transmission electron microscopy (TEM) and immunohistochemistry studies. OT prevented mean arterial pressure drop during early phase of ischemia and reperfusion. Treatment with OT before IR induction normalizes cardiomyocytes both in light microscopy and TEM observations. In addition, OT significantly reduced TUNEL- and increased Bcl-2-labeled positive cell number relative to IR (p<0.05). However, 5HD or ATRC inhibited the protective effects of OT on cardiomyocytes damaged by IR (p<0.05). Ultrastructural changes including extensive myofibril loss, sarcolemmal disruption and mitochondrial swelling due to amorphous dens bodies indicate necrosis induction in 5HD and ATRC as well as in IR groups. Restoration of immunohistochemistry parameters and protection against IR-induced ultrastructural changes confirm OT cardioprotective effects via mitoKATP channel and mPTP modulation in apoptosis induced by ischemia-reperfusion.     

Chemical Diversity of Essential Oils from Asteriscus graveolens (Forssk.) Less.: Identification of cis‐8‐Acetoxychrysanthenyl Acetate as a New Natural Component

Asteriscus graveolens is an endemic medicinal plant mainly distributed in south‐western Algeria and south‐eastern Morocco. The essential oils of leaves, stems, and flowers of A. graveolens had been studied by GC, GC/MS, and ¹³C‐NMR. The spectral data of two nerolidol derivatives, 6‐oxo‐ and 6‐hydroxycyclonerolidol, were reassigned by 1D‐ and 2D‐NMR spectroscopy. These compounds can be considered as chemical markers of this genus. The structure of a monoterpenic diester with a chrysanthenane skeleton, i.e., cis‐8‐acetoxychrysanthenyl acetate, was determined for the first time on the basis of GC/MS, and 1D‐ and 2D‐NMR. The stem and leaf oils were characterized by high content of oxygenated sesquiterpenes with 6‐oxo‐ and 6‐hydroxycyclonerolidol as major components, and the flower essential oils were dominated by the new monoterpenic compound cis‐8‐acetoxychrysanthenyl acetate.     

Effect of vitamin E on sperm number and testis histopathology of sodium arsenite-treated rats

The aims of this study were to investigate the adverse effects of sodium arsenite on the reproductive system of male rats as well as to examine whether vitamin E is able to ameliorate these effects. Adult rats were divided into four groups: 1/ control, 2/ sodium arsenite (8 mg/kg/day), 3/ vitamin E (100 mg/kg/day), and 4/ sodium arsenite +vitamin E group. Treatments were administered orally by gavage for eight weeks. After treatment, body and left testis weights were recorded and the testis was used for the histological analysis. Left cauda epididymis was used to count sperm number. Body and testis weight did not differ among the groups (p>0.05). A significant decrease (p<0.001) in sperm number and mean diameter of seminiferous tubules as well as a significant increase (p<0.001) in the mean diameter of seminiferous tubules' lumen were found in sodium arsenite group compared to those of controls. Sodium arsenite did not affect the morphology and diameter of spermatogonial nucleus (p>0.05). In the sodium arsenite + vitamin E group, vitamin E ameliorated (p<0.001) the adverse effects of sodium arsenite on sperm number as well as the diameters of tubule and lumen. In addition, the treatment of rats with vitamin E alone significantly (p<0.001) increased the diameter of seminiferous tubules and significantly (p<0.001) decreased seminiferous tubules' lumen compared to the control group. Vitamin E appeared to ameliorate the adverse effects of sodium arsenite on epididymal sperm number and some morphometrical parameters of the adult rat testis.     

Environmental effects of ozone depletion and its interactions with climate change: progress report, 2011

The parties to the Montreal Protocol are informed by three panels of experts. One of these is the Environmental Effects Assessment Panel (EEAP), which deals with two focal issues. The first focus is the effects of increased UV radiation on human health, animals, plants, biogeochemistry, air quality, and materials. The second focus is on interactions between UV radiation and global climate change and how these may affect humans and the environment. When considering the effects of climate change, it has become clear that processes resulting in changes in stratospheric ozone are more complex than believed previously. As a result of this, human health and environmental problems will be longer-lasting and more regionally variable. Like the other panels, the EEAP produces a detailed report every four years; the most recent was published in 2010 (Photochem. Photobiol. Sci., 2011, 10, 173-300). In the years in between, the EEAP produces less detailed and shorter progress reports, which highlight and assess the significance of developments in key areas of importance to the parties. The next full quadrennial report will be published in 2014-2015.     

Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers

Small animal fluorescence molecular imaging (FMI) can be a powerful tool for preclinical drug discovery and development studies¹. However, light absorption by tissue chromophores (e.g., hemoglobin, water, lipids, melanin) typically limits optical signal propagation through thicknesses larger than a few millimeters². Compared to other visible wavelengths, tissue absorption for red and near-infrared (near-IR) light absorption dramatically decreases and non-elastic scattering becomes the dominant light-tissue interaction mechanism. The relatively recent development of fluorescent agents that absorb and emit light in the near-IR range (600-1000 nm), has driven the development of imaging systems and light propagation models that can achieve whole body three-dimensional imaging in small animals³.Despite great strides in this area, the ill-posed nature of diffuse fluorescence tomography remains a significant problem for the stability, contrast recovery and spatial resolution of image reconstruction techniques and the optimal approach to FMI in small animals has yet to be agreed on. The majority of research groups have invested in charge-coupled device (CCD)-based systems that provide abundant tissue-sampling but suboptimal sensitivity^4-9, while our group and a few others^10-13 have pursued systems based on very high sensitivity detectors, that at this time allow dense tissue sampling to be achieved only at the cost of low imaging throughput. Here we demonstrate the methodology for applying single-photon detection technology in a fluorescence tomography system to localize a cancerous brain lesion in a mouse model.The fluorescence tomography (FT) system employed single photon counting using photomultiplier tubes (PMT) and information-rich time-domain light detection in a non-contact conformation¹¹. This provides a simultaneous collection of transmitted excitation and emission light, and includes automatic fluorescence excitation exposure control¹⁴, laser referencing, and co-registration with a small animal computed tomography (microCT) system¹⁵. A nude mouse model was used for imaging. The animal was inoculated orthotopically with a human glioma cell line (U251) in the left cerebral hemisphere and imaged 2 weeks later. The tumor was made to fluoresce by injecting a fluorescent tracer, IRDye 800CW-EGF (LI-COR Biosciences, Lincoln, NE) targeted to epidermal growth factor receptor, a cell membrane protein known to be overexpressed in the U251 tumor line and many other cancers¹⁸. A second, untargeted fluorescent tracer, Alexa Fluor 647 (Life Technologies, Grand Island, NY) was also injected to account for non-receptor mediated effects on the uptake of the targeted tracers to provide a means of quantifying tracer binding and receptor availability/density²⁷. A CT-guided, time-domain algorithm was used to reconstruct the location of both fluorescent tracers (i.e., the location of the tumor) in the mouse brain and their ability to localize the tumor was verified by contrast-enhanced magnetic resonance imaging.Though demonstrated for fluorescence imaging in a glioma mouse model, the methodology presented in this video can be extended to different tumor models in various small animal models potentially up to the size of a rat¹⁷.     

BMPR2 expression is suppressed by signaling through the estrogen receptor

Background

Low endogenous testosterone levels have been shown to be a risk factor for the development of cardiovascular disease and cardiovascular benefits associated with testosterone replacement therapy are being advocated; however, the effects of endogenous testosterone levels on acute coronary vasomotor responses to androgen administration are not clear. The objective of this study was to compare the effects of acute androgen administration on in vivo coronary conductance and in vitro coronary microvascular diameter in intact and castrated male swine.

Methods

Pigs received intracoronary infusions of physiologic levels (1?C100 nM) of testosterone, the metabolite 5??-dihydrotestosterone, and the epimer epitestosterone while left anterior descending coronary blood flow and mean arterial pressure were continuously monitored. Following sacrifice, coronary arterioles were isolated, cannulated, and exposed to physiologic concentrations (1?C100 nM) of testosterone, 5??-dihydrotestosterone, and epitestosterone. To evaluate effects of the androgen receptor on acute androgen dilation responses, real-time PCR and immunohistochemistry for androgen receptor were performed on conduit and resistance coronary vessels.

Results

In vivo, testosterone and 5??-dihydrotestosterone produced greater increases in coronary conductance in the intact compared to the castrated males. In vitro, percent maximal dilation of microvessels was similar between intact and castrated males for testosterone and 5??-dihydrotestosterone. In both studies epitestosterone produced significant increases in conductance and microvessel diameter from baseline in the intact males. Androgen receptor mRNA expression and immunohistochemical staining were similar in intact and castrated males.

Conclusions

Acute coronary vascular responses to exogenous androgen administration are increased by endogenous testosterone, an effect unrelated to changes in androgen receptor expression.     

Description of Meloidoderita salina sp. n. (Nematoda,Sphaeronematidae) from a micro-tidal salt marsh at?Mont-Saint-Michel Bay in France

Meloidoderita salina sp. n. is described and illustrated from the halophytic plant Atriplex portulacoides L. (sea purslane) growing in a micro-tidal salt marsh in the Mont-Saint-Michel Bay in France. This new species is the first member of Meloidoderita Poghossian, 1966 collected from a saline environment, and is characterized by the following features: sedentary mature females having a small swollen body with a clear posterior protuberance; slightly dorsally curved stylet, 19.9 µm long, with posteriorly sloping knobs; neck region irregular in shape and twisted; well developed secretory-excretory (S–E) pore, with markedly sclerotized S-E duct running posteriorly; prominent uterus bordered by a thick hyaline wall and filled with eggs. The adult female transforms into a cystoid. Eggs are deposited in both egg-mass and cystoid. Cystoids of Meloidoderita salina sp. n. display a unique sub-cuticular hexagonal beaded pattern. Male without stylet, pharyngeal region degenerated, S-E duct prominent, deirids small, developed testis 97.5 µm long, spicules 18.4 µm long, cloacal opening ventrally protruded, small phasmids posterior to cloaca opening and situated at 5.9 (3.2–7.7) µm from tail end, and conical tail ending in a rounded terminus marked with one (rarely two) ventrally positioned mucro. Additionally, some young malesof the new species were observed enveloped in the last J2 cuticle. Second-stage juvenile body 470 µm long, with a 16.4 µm long stylet, prominent rounded knobs set off from the shaft, hemizonid anterior and adjacent to S-E pore, small deirids located just above S-E pore level, genital primordium located at 68–77% of body length, phasmids small and located at about 19 µm from tail tip, and tail 38.7 µm long, tapering to finely pointed terminus with a finger-like projection. Phylogenetic analyses based on the nearly full length small subunit ribosomal DNA sequences of Meloidoderita salina sp. n. revealed a close relationship of the new species with Sphaeronema alni Turkina & Chizhov, 1986 and placed these two species sister to the rest of Criconematina.