Altered blood flow in terminal vessels after local application of ropivacaine and prilocaine

BACKGROUND: Ropivacaine is primarily a local anesthetic, but it also acts as a vasoactive agent. Case reports have described a critical reduction in blood flow when higher concentrations of ropivacaine were used for peripheral-nerve blocks. One hypothesis is that local application of ropivacaine in tissues supplied by end arteries reduces tissue blood flow because of arterial vasoconstriction. METHODS: Rats were anesthetized by inhalation of isoflurane. The tail vessels were carefully dissected from the ventral side near the radix. Randomly, normal saline, prilocaine 0.5%, prilocaine 0.5% with epinephrine 1:200,000, ropivacaine 0.2%, ropivacaine 0.5%, or ropivacaine 0.75% was applied directly to the artery. Blood flow in the tail was continuously measured by use of laser Doppler flowmetry distal to the surgical site. Changes in temperature in the tail were detected by use of infrared thermography. RESULTS: Blood flow decreased after the application of ropivacaine at all concentrations in comparison with normal saline (P < .01 at t = 10 minutes, P < .001 at t = 20, 30, and 40 minutes). This effect was most pronounced at t = 30 minutes for ropivacaine 0.5% (with a 64.5% decrease in blood flow). Prilocaine 0.5% with epinephrine 1:200,000 reduced blood flow by up to 44.7% (t = 20 minutes, P < .001). In comparison with the placebo, the application of ropivacaine 0.5% and 0.75%, as well as prilocaine 0.5% with epinephrine 1:200,000, caused a significant reduction in tail temperature (P < .001 at t = 20, 30, and 40 minutes). No alteration in blood flow or temperature was seen after application of prilocaine 0.5%. CONCLUSIONS: The application of ropivacaine directly to a rat's tail artery diminished blood flow and lowered regional skin temperature. These effects were dose related. The use of ropivacaine at higher concentrations can, therefore, not be recommended if tissues supplied by end arteries might be affected.     

The processing of prosody: Evidence of interhemispheric specialization at the age of four

Beyond its multiple functions in language comprehension and emotional shaping, prosodic cues play a pivotal role for the infant's amazingly rapid acquisition of language. However, cortical correlates of prosodic processing are largely controversial, even in adults, and functional imaging data in children are sparse. We here use an approach which allows to experimentally determine brain activations correlating to the perception and processing of sentence prosody during childhood. In 4-year-olds, we measured focal brain activation using near-infrared spectroscopy and demonstrate that processing prosody in isolation elicits a larger right fronto-temporal activation whereas a larger left hemispheric activation is elicited by the perception of normal language with full linguistic content. Hypothesized by the dual-pathway-model, the present data provide experimental evidence that in children specific language processes rely on interhemispheric specialization with a left hemispheric dominance for processing segmental (i.e. phonological) and a right hemispheric dominance for processing suprasegmental (i.e. prosodic) information. Generally in accordance with the imaging data reported in adults, our finding underlines the notion that interhemispheric specialization is a continuous process during the development of language.     

Two‐Year Neurodevelopment and Growth Outcomes for Preterm Neonates Who Received Low‐Dose Intravenous Soybean Oil

Background: In some studies, the dose of intravenous soybean oil (SO) has been associated with a decreased incidence of intestinal failure–associated liver disease. The effect of lipid sparing on neurodevelopment (ND) and growth remains unknown. This study investigated the impact of SO dose on ND and growth over the first 2 years of age in preterm neonates. Materials and Methods: This is a single‐site prospective follow‐up study. Neonates with a gestational age ≤29 weeks were randomized to low‐dose (LOW) or standard‐dose (CON) SO. Bayley Scales of Infant Development III and anthropometric measurements were collected at approximately 6, 12, and 24 months corrected gestational age. Results: Subjects were premature, with a mean (±SD) gestational age of 28 ± 1 and 27 ± 1 weeks (P = .3) for LOW and CON, respectively. Thirty subjects completed follow‐up (LOW = 15, CON = 15). There were no differences for ND and growth outcomes when LOW was compared with CON, with the exception of a higher 12‐month follow‐up cognitive scaled score in the LOW group (P = .02). Conclusion: A reduced SO dose did not adversely affect ND or growth in this cohort of preterm neonates. However, larger studies are needed to determine the long‐term safety of SO dose reduction before this strategy can be adopted.     

Chemopreventive effects of in vitro digested and fermented bread in human colon cells

Purpose

Bread as a staple food product represents an important source for dietary fibre consumption. Effects of wheat bread, wholemeal wheat bread and wholemeal rye bread on mechanisms which could have impact on chemoprevention were analysed in colon cells after in vitro fermentation.

Methods

Effects of fermented bread samples on gene expression, glutathione S-transferase activity and glutathione content, differentiation, growth and apoptosis were investigated using the human colon adenoma cell line LT97. Additionally, apoptosis was studied in normal and tumour colon tissue by determination of caspase activities.

Results

The expression of 76 genes (biotransformation, differentiation, apoptosis) was significantly upregulated (1.5-fold) in LT97 cells. The fermented bread samples were able to significantly increase glutathione S-transferase activity (1.8-fold) and glutathione content (1.4-fold) of the cells. Alkaline phosphatase activity as a marker of differentiation was also significantly enhanced (1.7-fold). The fermented bread samples significantly inhibited LT97 cell growth and increased the level of apoptotic cells (1.8-fold). Only marginal effects on apoptosis in tumour compared to normal tissue were observed.

Conclusions

This is the first study which presents chemopreventive effects of different breads after in vitro fermentation. In spite of differences in composition, the results were comparable between the bread types. Nevertheless, they indicate a potential involvement of this staple food product regarding the prevention of colon cancer.     

Expression of 5-HT3 receptors and TTX resistant sodium channels (NaV1.8) on muscle nerve fibers in pain-free humans and patients with chronic myofascial temporomandibular disorders

Background

Previous studies have shown that 5-HT₃-antagonists reduce muscle pain, but there are no studies that have investigated the expression of 5-HT₃-receptors in human muscles. Also, tetrodotoxin resistant voltage gated sodium-channels (Na_V) are involved in peripheral sensitization and found in trigeminal ganglion neurons innervating the rat masseter muscle. This study aimed to investigate the frequency of nerve fibers that express 5-HT_3A-receptors alone and in combination with Na_V1.8 sodium-channels in human muscles and to compare it between healthy pain-free men and women, the pain-free masseter and tibialis anterior muscles, and patients with myofascial temporomandibular disorders (TMD) and pain-free controls.

Methods

Three microbiopsies were obtained from the most bulky part of the tibialis and masseter muscles of seven and six healthy men and seven and six age-matched healthy women, respectively, while traditional open biopsies were obtained from the most painful spot of the masseter of five female patients and from a similar region of the masseter muscle of five healthy, age-matched women. The biopsies were processed by routine immunohistochemical methods. The biopsy sections were incubated with monoclonal antibodies against the specific axonal marker PGP 9.5, and polyclonal antibodies against the 5-HT_3A-receptors and Na_V1.8 sodium-channels.

Results

A similar percentage of nerve fibers in the healthy masseter (85.2%) and tibialis (88.7%) muscles expressed 5-HT_3A-receptors. The expression of Na_V1.8 by 5-HT_3A positive nerve fibers associated with connective tissue was significantly higher than nerve fibers associated with myocytes (P < .001). In the patients, significantly more fibers per section were found with an average of 3.8 ± 3 fibers per section in the masseter muscle compared to 2.7 ± 0.2 in the healthy controls (P = .024). Further, the frequency of nerve fibers that co-expressed Na_V1.8 and 5-HT_3A receptors was significantly higher in patients (42.6%) compared to healthy controls (12.0%) (P < .001).

Conclusions

This study showed that the 5-HT_3A-receptor is highly expressed in human masseter and tibialis muscles and that there are more nerve fibers that express 5-HT_3A-receptors in the masseter of women with myofascial TMD compared to healthy women. These findings indicate that 5-HT₃-receptors might be up-regulated in myofascial TMD and could serve as potential biomarkers of chronic muscle pain.     

Comparative in vitro activity of -ofloxacin and FK037 to other agents against 10,040 fresh clinical isolates

Fresh clinical isolates collected from November 1, 1992 through November 1, 1993, were tested by agar dilution against 26 different antimicrobial agents including FK037 and -ofloxacin. Among the 10 040 organisms tested were Staphylococcus aureus (n = 1222), methicillin-resistant Staphylococcus aureus (MRSA, n = 455), Staphylococcus epidermidis (n = 533), Staphylococcus hominis (n = 90), Staphylococcus hemolyticus (n = 89), Streptococcus pneumoniae (n = 144), Escherichia coli (n = 2326), Klebsiella pneumoniae (n = 745), Enterobacter cloacae (n = 258), Proteus mirabilis (n = 445), Pseudomonas aeruginosa (n = 998), and Stenotrophomonas (Xanthomonas) maltophilia (n = 102). Both -ofloxacin and FK037 inhibited 98% of S. aureus strains at 4 μg/ml. FK037 was at least 4 times more effective than the third generation cephalosporins against MRSA, inhibiting 79% of the strains at 16 μg/ml. While the potency of these agents looks promising, their clinical utility will depend in part upon the maximal dosage that can be safely administered.