Catecholamine and MHPG plasma levels,platelet MAO activity,and3H-imipramine binding in heroin and cocaine addicts

This work evaluated in a population of heroin and heroin plus cocaine human addicts:

1. Norepinephrine (NE), epinephrine (Epi), and 3-methoxy-4-hydroxyphenylglycol (MHPG) (the principal metabolite of brain NE) plasma levels;
2. Monoamine oxidase (MAO) activity; and
3. ³H-imipramine specific binding to the amine carrier in platelets.

NE plasma levels were significantly lower in the short-term heroin user groups (1–3 and 4–6 yr), a finding not observed in both the long-term heroin user (>6 yr) and heroin plus cocaine user (>6 yr) groups. Epi levels changed in a similar manner, except that a significant increase was noted in heroin plus cocaine abusers. Conversely, dopamine and MHPG plasma levels increased with the duration of heroin use, and even more with cocaine abuse. Platelet MAO activity increased in all groups. Specific³H-imipramine binding sites showed an increase after 3 yr of heroin abuse and in all heroin plus cocaine addicts. In conclusion, short-term use of heroin decreases NE or Epi release, but with prolonged use, a slow adpatation occurs. In contrast, cocaine inhibits the neuronal Epi uptake, even in a situation of long duration of abuse. Probably the amine levels additionally regulate the amine carrier, resulting in changes that show a different pattern from major depression. These drugs of abuse may also influence directly or indirectly related enzymatic systems.     

Trypanosoma cruzi: cloning and expression of an antigen recognized by acute and chronic human chagasic sera.

Here we describe the characterization of a Trypanosoma cruzi DNA sequence (clone A13) that codes for a polypeptide recognized by IgM and IgG antibodies from sera of acute and congenital chagasic patients. Antibodies to A13 antigen are also detected in the sera of chronic patients with different clinical forms of Chagas' disease, but not in sera of patients with leishmaniasis or other parasitic diseases. The antigenic determinants encoded by clone A13 are found in amastigotes and trypomastigotes of several T. cruzi strains, but not in the noninfective epimastigotes. The DNA sequence of the recombinant clone reveals one open reading frame encoding 251 amino acids without tandemly repeated sequences. Our data suggest that the A13 antigen may be useful for the development of serodiagnostic procedures.     

Isolation of genes mediating resistance to inhibitors of nucleoside and ergosterol metabolism in Leishmania by overexpression/selection

We tested a general method for the identification of drug resistance loci in the trypanosomatid protozoan parasite Leishmania major. Genomic libraries in a multicopy episomal cosmid vector were transfected into susceptible parasites, and drug selections of these transfectant libraries yielded parasites bearing cosmids mediating resistance. Tests with two antifolates led to the recovery of cosmids encoding DHFR-TS or PTR1, two known resistance genes. Overexpression/selection using the toxic nucleoside tubercidin similarly yielded the TOR (toxic nucleoside resistance) locus, as well as a new locus (TUB2) conferring collateral hypersensitivity to allopurinol. Leishmania synthesize ergosterol rather than cholesterol, making this pathway attractive as a chemotherapeutic target. Overexpression/selection using the sterol synthesis inhibitors terbinafine (TBF, targeting squalene epoxidase) and itraconazole (ITZ, targeting lanosterol C(14)-demethylase) yielded nine new resistance loci. Several conferred resistance to both drugs; several were drug-specific, and two TBF-resistant cosmids induced hypersensitivity to ITZ. One TBF-resistant cosmid encoded squalene synthase (SQS1), which is located upstream of the sites of TBF and ITZ action in the ergosterol biosynthetic pathway. This suggests that resistance to "downstream" inhibitors can be mediated by increased expression of ergosterol biosynthetic intermediates. Our studies establish the feasibility of overexpression/selection in parasites and suggest that many Leishmania drug resistance loci are amenable to identification in this manner.     

Bat flies (Diptera: Streblidae, Nycteribiidae) parasitic on bats (Mammalia: Chiroptera) at Parque Estadual da Cantareira, São Paulo, Brazil: parasitism rates and host-parasite associations

A total of 443 bat flies belonging to the families Nycteribiidae and Strelidae, were collected on 22 species of bats (Molossidae, Phyllostomidae, and Vespertilionidae) from Parque Estadual da Cantareira (S?o Paulo, Brazil), between January, 2000 and January, 2001. Eighteen new occurrences of bat flies were recorded on Anoura geoffroyi (Anastrebla caudiferae), Glossophaga soricina (A. caudiferae), Sturnira lilium (Trichobius phyllostomae, T. furmani, and Paraeuctenodes similis), Artibeus lituratus (A. caudiferae), A. fimbriatus (Megistopoda proxima), A. obscurus (Metelasmus pseudopterus), Myotis nigricans (M. proxima, M. aranea, Paratrichobius longicrus), M. ruber (Anatrichobius passosi, Joblingia sp.), M. levis (A. passosi), M. albescens (A. passosi, Basilia andersoni), and Histiotus velatus (M. aranea). Seven new occurrences were recorded for the state of S?o Paulo, increasing the range for T. tiptoni, T. furmani, M. proxima, Aspidoptera falcata, A. caudiferae, A. modestini and B. andersoni. The relationships between parasitism and host sex, reproductive stage, age hyperparasitism by fungi are discussed.     

Zooplankton and ichthyoplankton communities in a temperate estuary: spatial and temporal patterns

Zooplankton and ichthyoplankton assemblages were studied fromJanuary 2003 to June 2004 in a temperate shallow estuary (Mondegoestuary, Portugal). Monthly sampling was performed at five stationsat high and low tides, with subsurface tows with 335 and 500µm mesh Bongo nets. Analysis of variance (ANOVA) showeda significant effect (P < 0.05) of the mesh size of the neton the abundance of main zooplankton groups. On average, theabundance of the 500 µm taxocenosis was 67 and 102 timeslower than the 335 µm taxocenosis at high and low tidesrespectively, especially in the south arm. More than 80 specieswere identified in the zooplankton samples. The upper reachesof northern arm are dominated by freshwater crustacean mesozooplanktonlike Acanthocyclops robustus and Diaptomus spp. and the cladoceransDaphnia, Ceriodaphnia and Bosmina, often being codominant. Inthe southern arm, the resident estuarine copepod Acartia tonsawas dominant, eventually being the most abundant taxon. Marinereaches of estuary are usually dominated by the marine calanoidcopepods Acartia clausi and Temora longicornis and the siphonophoresMuggiaea atlantica. Concerning the ichthyoplankton, this wasdominated by the larvae of estuarine resident species, mainlyPomatoschistus sp., and eggs of Engraulis encrasicolus. Theabundance of Pomatoschistus sp. larvae was positively correlatedwith water temperature. Statistical analysis (canonical correspondenceanalysis) used to determine the spatiotemporal structure ofthe zooplankton assemblages and its correlation with environmentalvariables showed that salinity and temperature were the mainfactors influencing the distribution of zooplankton. The resultsobtained also showed that abundance was strongly influencedby the hydrological circulation pattern and direct or indirecthuman impacts that occur in each arm of the estuary. This article was presented at Plankton Symposium III, held atFiguera da Foz, portugal, between 17 and 20 March 2005, underthe auspices of the University of Coimbra and the Universityof Aveiro, and coordinated by Mário Jorge Pereira andUlisses M. Azeiteiro.     

Taurine supplementation prevents morpho-physiological alterations in high-fat diet mice pancreatic β-cells

Taurine (Tau) is involved in beta (β)-cell function and insulin action regulation. Here, we verified the possible preventive effect of Tau in high-fat diet (HFD)-induced obesity and glucose intolerance and in the disruption of pancreatic β-cell morpho-physiology. Weaning Swiss mice were distributed into four groups: mice fed on HFD diet (36 % of saturated fat, HFD group); HTAU, mice fed on HFD diet and supplemented with 5 % Tau; control (CTL); and CTAU. After 19 weeks of diet and Tau treatments, glucose tolerance, insulin sensitivity and islet morpho-physiology were evaluated. HFD mice presented higher body weight and fat depots, and were hyperglycemic, hyperinsulinemic, glucose intolerant and insulin resistant. Their pancreatic islets secreted high levels of insulin in the presence of increasing glucose concentrations and 30 mM K⁺. Tau supplementation improved glucose tolerance and insulin sensitivity with a higher ratio of Akt phosphorylated (pAkt) related to Akt total protein content (pAkt/Akt) following insulin administration in the liver without altering body weight and fat deposition in HTAU mice. Isolated islets from HTAU mice released insulin similarly to CTL islets. HFD intake induced islet hypertrophy, increased β-cell/islet area and islet and β-cell mass content in the pancreas. Tau prevented islet and β-cell/islet area, and islet and β-cell mass alterations induced by HFD. The total insulin content in HFD islets was higher than that of CTL islets, and was not altered in HTAU islets. In conclusion, for the first time, we showed that Tau enhances liver Akt activation and prevents β-cell compensatory morpho-functional adaptations induced by HFD.     

mTOR Inhibition Prevents Epithelial Stem Cell Senescence and Protects from Radiation-Induced Mucositis

The integrity of the epidermis and mucosal epithelia is highly dependent on resident self-renewing stem cells, which makes them vulnerable to physical and chemical insults compromising the repopulating capacity of the epithelial stem cell compartment. This is frequently the case in cancer patients receiving radiation or chemotherapy, many of whom develop mucositis, a debilitating condition involving painful and deep mucosal ulcerations. Here, we show that inhibiting the mammalian target of rapamycin (mTOR) with rapamycin increases the clonogenic capacity of primary human oral keratinocytes and their resident self-renewing cells by preventing stem cell senescence. This protective effect of rapamycin is mediated by the increase in expression of?mitochondrial superoxide dismutase (MnSOD), and the consequent inhibition of ROS formation and oxidative stress. mTOR inhibition also protects from the loss of proliferative basal epithelial stem cells upon ionizing radiation in?vivo, thereby preserving the integrity of the oral mucosa and protecting from radiation-induced mucositis.     

Evidence for Changes in Estuarine Zooplankton Fostered by Increased Climate Variance

Estuaries are among the most valuable aquatic systems in terms of their services to human welfare. They offer an ideal framework to assess multiscale processes linking climate and food web dynamics through the hydrological cycle. Resolving food web responses to climate change is fundamental to resilience management of these threatened ecosystems under global change scenarios. Here, we examined the temporal variability of the plankton food web in the Mondego Estuary, central Iberian Peninsula, over the period 2003 to 2012. The results pointed out a cascading effect from climate to plankton communities that follow a non-stationary behavior shaped by the climate variance envelope. Concurrent changes in hydrographic processes at the regional, that is, upwelling intensity, and local, that is, estuarine hydrology, scales were driven by climatic forcing promoted by the North Atlantic Oscillation; the influence of which permeated the physical environment in the estuary affecting both autotrophic and heterotrophic communities. The most conspicuous change arose around 2008 and consisted of an obvious decrease in freshwater taxa along with a noticeable increase in marine organisms, mainly driven by gelatinous zooplankton. The observed increase in small-sized cosmopolitan copepods, that is, Clausocalanus arcuicornis, Oithona plumifera, thermophilic species, that is, Penilia avirostris, and gelatinous zooplankton suggests a structural change in the Mondego plankton community. These results provide empirical support to the expectation that expanding climate variance changes plankton structure and functioning, likely fostering trophic interactions in pelagic food webs.