The Appearance of Endothelium in Small Arteries After Treatment with 5-Fluorouracil. An Electron Microscopic Study of Late Effects in Rabbits

Cardiotoxicity is an unexplained toxic manifestation of 5-fluorouracil (5-FU). Its possible mechanism could be a direct cytotoxic effect on the vascular endothelium. We have tested this hypothesis in an experimental study in rabbits, using scanning and transmission electron microscopic evaluation of endothelium in small arteries (the central artery of the ear). The perfusion fixation method at physiological pressure and temperature was used. Both local and systemic effects of 5-FU on endothelium were studied 1, 3, 7, 14 and 30 days after in vivo treatment with 5-FU. Fifteen rabbits were used and five additional animals served as controls. The following parameters were evaluated: vessel wall and endothelial cell contraction, cell oedema, cytolysis, occurrence of denuded areas, platelet adhesion/aggregation and fibrin formation. For the description of each parameter, a scale of negative points (0.0-3.0) was used. We found severe cell damage with accompanying thrombus formation. The findings support the hypothesis that the thrombogenic effect of 5-FU, secondary to its direct cytotoxic effect on endothelium, is the pathophysiological mechanism behind 5-FU cardiotoxicity

The Lactobacillus flora in vagina and rectum of fertile and postmenopausal healthy Swedish women

<p>Abstract</p> <p>Background</p> <p><it>Lactobacillus </it>species are the most often found inhabitants of vaginal ecosystem of fertile women. In postmenopausal women with low oestrogen levels, <it>Lactobacillus </it>flora is diminishing or absent. However, no studies have been performed to investigate the correlation between oestrogen levels and the lactobacilli in the gut. The aim of the present study was to investigate the relation in healthy women between vaginal and rectal microbial flora as well as possible variations with hormone levels.</p> <p>Methods</p> <p>Vaginal and rectal smears were taken from 20 healthy fertile women, average 40 years (range 28-49 years), in two different phases of the menstrual cycle, and from 20 postmenopausal women, average 60 years (range 52-85 years). Serum sex hormone levels were analyzed. Bacteria from the smears isolated on Rogosa Agar were grouped by Randomly Amplified Polymorphic DNA and identified by multiplex PCR and partial 16S rRNA gene sequencing.</p> <p>Results</p> <p><it>Lactobacillus crispatus </it>was more often found in the vaginal flora of fertile women than in that of postmenopausal (p = 0.036). Fifteen of 20 fertile women had lactobacilli in their rectal smears compared to 10 postmenopausal women (p = 0.071). There was no correlation between the number of bacteria in vagina and rectum, or between the number of bacteria and hormonal levels. Neither could any association between the presence of rectal lactobacilli and hormonal levels be found.</p> <p>Conclusion</p> <p><it>Lactobacillus crispatus </it>was more prevalent in the vaginal flora of fertile women, whereas the <it>Lactobacillus </it>flora of rectum did not correlate to the vaginal flora nor to hormonal levels.</p

β-Lactam Effects on Mixed Cultures of Common Respiratory Isolates as an Approach to Treatment Effects on Nasopharyngeal Bacterial Population Dynamics

BACKGROUND: Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae are bacteria present in the nasopharynx as part of normal flora. The ecological equilibrium in the nasopharynx can be disrupted by the presence of antibiotics. METHODOLOGY/PRINCIPAL FINDINGS: A computerized two-compartment pharmacodynamic model was used to explore beta-lactam effects on the evolution over time of a bacterial load containing common pharyngeal isolates by simulating free serum concentrations obtained with amoxicillin (AMX) 875 mg tid, amoxicillin/clavulanic acid (AMC) 875/125 mg tid and cefditoren (CDN) 400 mg bid regimens over 24 h. Strains and MICs (microg/ml) of AMX, AMC and CDN were: S. pyogenes (0.03, 0.03 and 0.015), S. pneumoniae (2, 2 and 0.25), a beta-lactamase positive H. influenzae (BL(+); >16, 2 and 0.06) and a beta-lactamase positive AMC-resistant H. influenzae (BLPACR, >16, 8 and 0.06). Mixture of identical 1:1:1:1 volumes of each bacterial suspension were prepared yielding an inocula of approximately 4 x 10(6) cfu/ml. Antibiotic concentrations were measured both in bacterial and in bacteria-free antibiotic simulations. beta-lactamase production decreased AMX concentrations and fT(>MIC) against S. pneumoniae (from 43.2% to 17.7%) or S. pyogenes (from 99.9% to 24.9%), and eradication was precluded. The presence of clavulanic acid countered this effect of co-pathogenicity, and S. pyogenes (but not BL(+) and S. pneumoniae) was eradicated. Resistance of CDN to TEM beta-lactamase avoided this co-pathogenicity effect, and CDN eradicated S. pyogenes and H. influenzae strains (fT(>MIC) >58%), and reduced in 94% S. pneumoniae counts (fT(>MIC) approximately 25%). CONCLUSIONS/SIGNIFICANCE: Co-pathogenicity seems to be gradual since clavulanic acid countered this effect for strains very susceptible to AMX as S. pyogenes but not for strains with AMX MIC values in the limit of susceptibility as S. pneumoniae. There is a potential therapeutic advantage for beta-lactamase resistant cephalosporins with high activity against streptococci

Frost hardiness in bark and needles of Norway spruce in southern Sweden

Bark necrosis and resin flows in Norway spruce have increased in southern Sweden over the last few decades. Frost damage late in spring has been suggested as a possible cause, but other factors besides the climate may have contributed to the damage. The nutrient status influences the hardening processes and plants with poor nutritional conditions have an increased sensitivity to frost. In this study the sensitivity to frost of bark and the hardiness status of needles of Norway spruce were compared with the nutrient status at two sites with different soil fertility. The trees were 30-40 years old. The hardiness status of the bark and needles was negatively affected by low concentrations of P and Mg

The use of light and electron microscopy to assess the impact of ozone on Norway spruce needles

Light (LM) and transmission electron (TEM) microscopy were used to study previously specified ozone symptoms in the foliage of Norway spruce. The three youngest green needle generations from twenty mature trees in two stands on sites of different soil fertility at Asa, southern Sweden, were sampled in 1999. The critical dose of ozone, expressed as AOT40, was 6362 ppb.h. LM showed ozone-specific symptoms: decreased chloroplast size with electron dense stroma advancing gradually from the outer to the inner cell layers, being most severe in the needle side facing the sky. The symptoms were expressed as ozone syndrome indices at the needle generation, tree and stand levels. The index had higher values at the low fertility site. TEM was used to confirm the LM results. The study shows that LM can be used for diagnosis of the impact of ozone on conifers in the field