Increased GH responsiveness to dopamine receptor stimulation in alcohol addicts during the late withdrawal syndrome

In humans the release of growth hormone (GH) elicited by dopamine (DA) and DA agonists may represent a reliable model to assess change in sensitivity of DA receptors. We now report that in chronic alcoholics, 4–7 days after the suspension of alcohol consumption, the increase of GH response to DA infusion was higher than that seen in non alcoholic volunteers. The specificity of this GH response to DA administration was demonstrated by the use of domperidone, a novel peripheral antagonist of DA receptors. These results suggest the development of hyper-responsiveness of DA receptors involved in the control of GH secretion in chronic alcoholics during the later phases of the “withdrawal syndrome”.     

Premature labor and indomethacin

Administration of indomethacin to 29 women in the 26th–37th week of gestation with premature labor contractions was followed in 26 by a significant decrease of uterine activity. The effect of therapy was monitored by serial external tocometry recordings and by plasma concentrations of estriol, h.P.L., alpha-fetoprotein, and estriol/creatinine ratio in urine. The labor was monitored by cardiotocography; the newborn infants were examined by the pediatrician. Following oral indomethacin treatment (25 mg every 6 Hours for 5 days) no untoward effects was observed on maternal and fetal wellbeing during pregnancy and labor. Four out 29 newborn infants, all appropriate for gestational age of 36–40 weeks, had one-minute Apgar scores less than 7, cyanosis, tachypnea, hypoxemia and serious oxygen dependency for several days. All the infant survived. These abnormalities may be due to short-term exposure to indomethacin and consequent inhibition of cyclo-oxygenase, impairement of prostaglandin-dependent physiological regulation of vessel tone during fetal life and circulatory disorders at birth.     

Richness and composition of Calliphoridae in an Atlantic Forest fragment: implication for the use of dipteran species as bioindicators

Studies measuring the damage in degraded environments have increased, and it is necessary to obtain reliable biological and ecological indicators for the recovery of such degraded environments and subsequent preservation. This study aimed to conduct a survey of local insects and evaluate their utility in monitoring forest restoration in a degraded area in the Atlantic Forest biome in Ribeirao Grande, State of São Paulo, Brazil. Collections with Shuey traps were conducted from 2006 to 2011 in four distinct forest fragments characterized by environmental impacts, human actions, and phytophysiognomic profiles: Forest (FO), a preserved area with native plant species; “Capoeira” (CA), an area in the natural regeneration process; Planting (PL), an area reforested with native plants; and Pasture (PA), an area with only shrubs. A total of 2,456 specimens of Calliphoridae (Diptera) were collected. Mesembrinella bellardiana was the most abundant (n = 1,884) and dominant species in all environments sampled. The relative abundance of M. bellardiana in the most preserved environment (60.2 % FO, 24.4 % CA, 8.6 % PL, and 6.7 % PA) and other ecological parameters showed that it could be a bioindicator species, i.e., data on its presence or absence directly reflected the status of local preservation. Information on Neotropical dipterans associated with the forested environment is very scarce in the literature. To our knowledge, this is the first study describing the occurrence of Calliphora lopesi (Calliphoridae) in the State of São Paulo.     

The X-ray crystallographic structure of the angiogenesis inhibitor angiostatin

Angiogenesis inhibitors have gained much public attention recently as anti-cancer agents and several are currently in clinical trials, including angiostatin (Phase I, Thomas Jefferson University Hospital, Philadelphia, PA). We report here the bowl-shaped structure of angiostatin kringles 1-3, the first multi-kringle structure to be determined. All three kringle lysine-binding sites contain a bound bicine molecule of crystallization while the former of kringle 2 and kringle 3 are cofacial. Moreover, the separation of the kringle 2 and kringle 3 lysiner binding sites is sufficient to accommodate the alpha-helix of the 30 residue peptide VEK-30 found in the kringle 2/VEK-30 complex. Together the three kringles produce a central cavity suggestive of a unique domain where they may function in concert.     

Binding of beta-carbolines at 5-HT(2) serotonin receptors

A series of ring-substituted (i.e., methoxy and bromo) 3,4-dihydro- and 1,2,3,4-tetrahydro-β-carbolines was examined at 5-HT_2A and 5-HT_2C serotonin receptors. Whereas most of the methoxy-substituted derivatives typically displayed affinities similar to their unsubstituted parents, certain (particularly 8-substituted) bromo derivatives displayed enhanced affinity. A binding profile was obtained for selected β-carbolines.     

Large-scale purification of recombinant human angiostatin

A process for the purification of recombinant human angiostatin (rhAngiostatin), produced by Pichia pastoris fermentation operated at the 2000-L scale, is reported. rhAngiostatin was recovered and purified directly from crude fermentation broth by cation exchange expanded bed adsorption chromatography. Anion exchange chromatography, hydroxyapatite chromatography, and hydrophobic interaction chromatography were used for further purification. Full-length rhAngiostatin was separated from rhAngiostatin molecules fragmented by endoproteolysis. On average, 140 g of rhAngiostatin was produced per batch, with an overall yield of 59% (n = 9). The purification process was completed in approximately 48 h and used only inexpensive and nontoxic raw materials. Methods development, process synthesis, and process scale-up data are presented and discussed.     

Blood biomarkers role in acute ischemic stroke patients: higher is worse or better?

Background

Thrombolytic therapy (TT) for acute ischemic stroke (AIS) can provoke bleeding’s complication depending on the ischemic lesion (IL) dimension. Inflammation involved in the setting of acute ischaemic stroke, is associated with infarct size. We aimed to study the independent correlation and association between clinical panel of routinely identified biomarkers, including inflammatory parameters, and cerebral IL dimension and site.

Results

We evaluated eleven biomarkers in 105 unrelated patients during their hospitalization after acute stroke event. Our data indicate a significant association of: a) confluent IL size with 4th quartile of Erythrocyte Sedimentation Rate (ESR) (OR = 5.250; 95% CI, 1.002 to 27.514) and an independent correlation with sex; b) confluent IL size with 3rd quartile of fibrinogen (OR = 5.5; 95% CI, 1.027 to 29.451); c) confluent IL size with 3rd quartile of platelets (OR= 0.059; 95% CI, 0.003 to 1.175) and independent correlation with sex; d) smaller IL size (OR = 5.25; 95% CI, 1.351 to 20.396) with 3rd quartile of albumin levels and nodular and parenchimal IL size with 2nd (OR = 0.227; 95% CI, 0.053 to 0.981), 3rd (OR = 0.164; 95% CI, 0.038 to 0.711) and 4th (OR = 0.205; 95% CI, 0.048 to 0.870) quartiles albumin levels; e) smaller IL size with 3rd quartile triglycerides (TG) levels (OR = 9; 95% CI, 2.487 to 32.567) and an independent correlation with anterior location. Smaller IL size, anterior AIS turned out to be independently correlated with high serum albumin levels. Finally, high INR and PTT values were associated with worse NIHSS clinical outcomes in contrast to that observed with higher albumin level.

Conclusions

We provide evidence of routine biomarkers levels correlation with acute IL size, independently of age and sex. In addition, we highlight the importance of differentiation of biomarkers normal interval levels for further improvement not only of the clinical decision making but also in post-acute clinical outcome management.

     

The distance dependence prediction of the Janzen-Connell hypothesis: a meta-analysis

The Janzen-Connell hypothesis explains the maintenance of tropical diversity through the interacting effects of parent-centered dispersal patterns and distance- and density-dependent propagule survival. These effects were thought to support regular spacing of species within tropical forest, enhancing diversity. One of the predictions of the hypothesis is that seed and seedling survival should improve with increased parental distance. Although there are many independent tests of this hypothesis for individual species, there are few synthetic studies that have brought these data together to test its validity across species. This paper reports the results of a meta-analysis of the effect of distance on enhancing propagule survival, employing an odds-ratio effect size metric. We found no general support for the distance-dependent prediction of the hypothesis, and conclude that further testing to explore this hypothesis as a diversity-maintaining mechanism is unnecessary. However, we did find that distance from parent slightly reduces survivorship in the temperate zone, as contrasted with the tropics, and we saw stronger evidence in support of the hypothesis for seedlings than for seeds. The phenomenon of enhanced propagule survival with distance from the parent may be important for the population biology of particular species, but it is not a general phenomenon across communities, life history stages or life forms.     

A standard tissue as a control for histochemical and immunohistochemical staining

The variable quality of histochemical and immunohistochemical staining of tissues may be attributed to pre-analytical and analytical variables. Both categories of variables frequently are undefined or inadequately controlled during specimen collection and preparation. Pre-analytical variables may alter the molecular composition of tissues, which results in variable staining; such variations may cause problems when different tissues are used as staining controls. We developed a standard tissue for use as a staining control. Our standard tissue contains five components: 1) nine combined human cell lines mixed with stroma from human spleen; 2) a squamous cancer cell line, A431; 3) fungus; 4) transverse sections of the mosquitofish and 5) normal human spleen. The first three components were embedded in HistoGel^? and all components were processed to paraffin and used to construct a single standard paraffin block. The muscles of mosquitofish and arteries of the spleen are positive controls for eosin staining, while other tissues are useful for assessing hematoxylin staining. The mosquitofish tissues also are excellent controls for the Masson trichrome stain and all mucin-related histochemical stains that we tested. The goblet cells of the intestine and skin stained strongly with Alcian blue, pH 2.5 (AB-2.5), mucicarmine, colloidal iron, periodic acid Schiff (PAS) or PAS-hematoxylin (PASH) and combination stains such as colloidal iron-PASH. Cell lines were not useful for evaluating histochemical stains except for PASH. The splenic stroma was a useful control for AB-2.5; however, eosin and mucin stains stained cell lines poorly, probably due to their rapid growth and associated loss of some differentiated characteristics such as production of mucins. Nevertheless, the cell lines were a critical control for immunohistochemical stains. Immunostaining of specific cell lines was consistent with the presence of markers, e.g., EGFr in DU145 cells. The cell lines expressed a wide range of markers, so they were useful controls for immunohistochemical staining including EGFr, HER2, E-cadherin, cytokeratins, Ki67, PCNA, estrogen receptor, progesterone receptor, CD3, CD20 and CD45, activated (cleaved) caspase 3 and Bcl-2. The cell lines also were a control for the TUNEL stain.