Developmental Exposure to Fluoxetine Modulates the Serotonin System in Hypothalamus

The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLU, Prozac®) is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured)) on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks) until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation) of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.     

Prevention of recurrent acute cystitis by methenamine hippurate: double blind controlled crossover long term study.

In a randomised, double blind, long term, crossover study 1 g twice daily of methenamine hippurate was compared with placebo for its preventive effect on recurrent attacks of acute cystitis. Methenamine hippurate and placebo were interchanged every six months for two years. During one of the years patients took 250 ml extra fluid every morning and evening. Out of 21 enrolled patients, 14 completed the first year and 13 both years of treatment, which permitted the evaluation of 27 patient years. There were 52 episodes of acute cystitis caused by reinfection: 41 occurred during placebo treatment and only 11 during the methenamine hippurate regimen (p less than 0.01). Extra fluid intake did not reduce the incidence of acute cystitis, nor did it reduce the effect of methenamine hippurate. Methenamine hippurate is an effective prophylactic agent against recurrent acute cystitis and has the advantage of not inducing cross resistance to conventional antibiotics.     

Surface-induced aggregation of ferritin. Concentration dependence of adsorption onto a hydrophobic surface

The isotherm of ferritin adsorption onto a hydrophobic surface was studied by transmission electron microscopy. Adsorbed ferritin was found to be distributed in molecular clusters. The adsorption process was diffusion-rate-limited after 20 h adsorption time at bulk concentrations below 1 mg/1. The clusters formed during the diffusion-rate-limited adsorption had a fractal dimension D approximately 1.0 when averaged over all clusters. The pair distribution function g(r) showed an increased probability of finding nearest neighbours at distances less than 30 nm. The surface concentration of adsorbed ferritin was weakly dependent on the bulk concentration of ferritin in the range 10 mg/1-10 g/1 and the average number of nearest neighbour molecules was constant in this concentration range. The mass distribution of adsorbed ferritin c(r) had a fractal dimension D = 1.8 at a bulk concentration of 10 g/l and a surface concentration corresponding to theta = 0.45 +/- 0.05. The pair correlation function g(r) showed decreasing probability of finding nearest neighbour molecules over long distances as in percolating clusters. The results indicate that ferritin adsorbs strongly to the surface at low surface concentrations and weakly at high surface concentrations. The stability of ferritin adsorption was correlated to the average number of nearest neighbour molecules, indicating a possibility that desorption is a critical supramolecular phenomenon.     

Bacterioplankton in the acidified Lake Gårdsjön

Total bacterial numbers in different strata of lake water and in inlet and outlet streams have been recorded during a yearly cycle. A calculated mean cell volume of 0.342 µm² has then been used to estimate bacterial biomass in the lake. Change of biomass during the year was substantial and the range was from about 0.1 g · m^–3 to about 1.0–1.2 g · m^–3. The seasonal development included a spring-early summer increase followed by a decrease to the minimum in July–August. Correlation between epi- and hypolimnion was high and in both strata two dominant autumn peaks in biomass appeared. With the exception of the last autumn peak the development of bacterial biomass was closely related to development of phytoplankton biomass and production.     

Antigenic variation of pilin regulates adhesion of Neisseria meningitidis to human epithelial cells

Pili have been shown to play an essential role in the adhesion of Neisseria meningitidis to epithelial cells. However, among piliated strains, both inter- and intrastrain variability exist with respect to their degree of adhesion to epithelial cells in vitro (Virji et al., 1992). This suggests that factors other than the presence of pili per se are involved in this process. The N. meningitidis pilin subunit undergoes extensive antigenic variation. Piliated low- and high-adhesive derivatives of the same N. meningitidis strain were selected and the nucleotide sequence of the pilin gene expressed in each was determined. The highly adhesive derivatives had the same pilin sequence. The alleles encoding the pilin subunit of the low-adhesive derivatives were completely different from the one found in the high-adhesive isolates. Using polyclonal antibodies raised against one hyperadhesive variant, it was confirmed that the low-adhesive piliated derivatives expressed pilin variants antigenically different from the highly adhesive strains. The role of antigenic variation in the adhesive process of N. meningitidis was confirmed by performing allelic exchanges of the pilE locus between low-and high-adhesive isolates. Antigenic variation has been considered a means by which virulent bacteria evade the host immune system. This work provides genetic proof that a bacterial pathogen, N. meningitidis, can use antigenic variation to modulate their degree of virulence.     

Amino acid and lactate catabolism in trimethylamine oxide respiration of Alteromonas putrefaciens NCMB 1735

The nonfermentative Alteromonas putrefaciens NCMB 1735 grew anaerobically in defined media with trimethylamine oxide as external electron acceptor. All amino acids tested, except taurine and those with a cyclic or aromatic side chain, were utilized during trimethylamine oxide-dependent anaerobic growth. Lactate, serine, and cysteine (which are easily converted to pyruvate) and glutamate and aspartate (which are easily converted to tricarboxylic acid cycle intermediates) were metabolized at the fastest rate. Growth with lactate as growth-limiting substrate gave rise to the formation of 40 mol% acetate, whereas serine and cysteine were nearly completely oxidized to CO2. Molar growth yields with the latter substrates were the same and were 50% higher than with lactate. This showed that more ATP was formed when acetyl coenzyme A entered the tricarboxylic acid cycle than when it was converted via acetyl phosphate to acetate. Also, growth with formate as substrate indicated that the reduction of trimethylamine oxide to trimethylamine was coupled with energy conservation by a respiratory mechanism.