Neural delay in the ascending auditory pathway

Summary Evoked responses from the cochlea and cochlear nucleus in the rat were studied using two types of stimuli: (1) bursts of tones or noise, and (2) continuous tones or noise that were amplitude modulated with pseudorandom noise. While the responses to the first type of stimuli were averaged only in the conventional way, the responses to the continuous and amplitude modulated sounds were averaged over one period of the pseudorandom noise. This average was then cross correlated with one period of the noise. The morphology of these cross correlation functions was in many ways similar to the response to transient sounds.Recordings from the round window of the cochlea and the cochlear nucleus showed that the latencies of these peaks in the responses to tone bursts and those of the cross correlation functions obtained from the continuous tones modulated with pseudorandom noise were similar. However, the latencies of the peaks in the cross correlation functions were slightly shorter and showed less dependency on the stimulus intensity than did the peaks in the responses to tone bursts. When the responses to noise bursts and the responses to noise that was amplitude modulated were compared, it was found that the latencies of the peaks in the cross correlation functions were nearly independent of the stimulus intensity. However, the peaks in the averaged responses to noise bursts showed a decrease in latency with increasing sound intensity.Supported in part by a grant from the Deafness Research Foundation     

Potential of macrolide antibiotics to inhibit protein synthesis of Pseudomonas aeruginosa: suppression of virulence factors and stress response

Recently we have reported that sub-minimum inhibitory concentrations (MICs) of macrolide antibiotics, such as erythromycin, clarithromycin, and azithromycin, induce loss of viability of Pseudomonas aeruginosa with longer incubation periods. In the present study we examined the effects of sub-MICs of macrolide antibiotics on protein synthesis and the expression of heat shock proteins (Gro-EL) in P. aeruginosa and the association of these factors with the viability of P. aeruginosa. In seven strains of P. aeruginosa clinical isolates, inhibition of protein synthesis was generally observed in bacteria grown on agar with sub-MIC azithromycin (8 μg/ml) at 24 h, and this was followed by loss of viability after an additional 24-h incubation. The inhibition of protein synthesis was shown in bacteria treated with sub-MICs of erythromycin and clarithromycin, but not with sub-MICs of other antibiotics examined (josamycin, tobramycin, ofloxacin, clindamycin, and ceftazidime) even at relatively high sub-MICs. In the heat shock condition (45°C), strong expression of the heat shock protein Gro-EL was induced in bacteria grown on antibiotic-free medium, whereas there was a delay of such a response in bacteria exposed to 4 μg/ml of azithromycin. Reflecting these results, an abrupt reduction of viability in azithromycin-treated bacteria was observed within 3 h in the heat shock condition. Western blot analysis, using specific antibody for Gro-EL, demonstrated that erythromycin, clarithromycin, and azithromycin, at concentrations of 0.5–2 μg/ml, inhibited the expression of lower-molecular weight Gro-EL bands in the constitutive state. These results indicated that macrolides, at concentrations far below the MICs, suppressed protein synthesis in P. aeruginosa, an effect which may be associated with the inhibition of P. aeruginosa virulence and its loss of viability with longer incubation. Moreover, it is likely that the macrolides may sensitize bacteria to stresses, as these antibiotics induced alterations in a major stress protein, Gro-EL, in constitutive and inducible states. Received: September 13, 1999 / Accepted: December 7, 1999     

Cyclodextrin metal-organic framework as vaccine adjuvants enhances immune responses

It is urgently needed to develop novel adjuvants for improving the safety and efficacy of vaccines. Metal-organic frameworks (MOFs), with high surface area, play an important role in drug delivery. With perfect biocompatibility and green preparation process, the γ-cyclodextrin metal-organic framework (γ-CD-MOF) fabricated with cyclodextrin and potassium suitable for antigen delivery. In this study, we modified γ-CD-MOF with span-85 to fabricate the SP-γ-CD-MOF as animal vaccine adjuvants. The ovalbumin (OVA) as the model antigen was encapsulated into particles to investigate the immune response. SP-γ-CD-MOF displayed excellent biocompatibility in vitro and in vivo. After immunization, SP-γ-CD-MOF loaded with OVA could induce high antigen-specific IgG titers and cytokine secretion. Meanwhile, SP-γ-CD-MOF also significantly improved the proliferation of spleen cells and activated and matured the bone marrow dendritic cells (BMDCs). The study showed the potential of SP-γ-CD-MOF in vaccine adjuvants and provided a novel idea for the development of vaccine adjuvants.     

内皮─氧化氮的减少引起Dahl高血压大鼠异常的血管反应

本文研究目的在于观察Dahl高血压大鼠对去甲肾上腺素（NE）收缩反应增强，对乙酰胆碱（ACH）舒张反应减弱，是否与血管内皮NitricOxide（NO）有关。7—8周龄雄性Dahl盐敏感（DS）大鼠和盐抵抗（DR）大鼠，各随机分两组，分别给予正常盐或高盐饮食，每周尾套管法测血压和体重，4周后麻醉状态下取胸主动脉，用于离体血管反应性研究。结果显示：高盐饮食的DS大鼠尾动脉血压明显升高，NE诱导的收缩反应也明显高于其它三组，去内皮及体外L—NAME的处理，可以消除这一差别。同时Dahl高血压大鼠，ACh诱导的舒张反应也明显减弱。体外Larginine的使用，不同程度地降低了NE诱导的收缩反应，但不能废除组间差异。结论：NO合成酶功能障碍可能是Dahl高血压大鼠异常血管反应的原因。     

Lack of colonic inflammation-induced acute visceral hypersensitivity to colorectal distension in Nav1.9 knockout mice

Tetrodotoxin-resistant voltage-gated sodium channels subtype 9 (Na_v1.9) are expressed in small-diameter dorsal root ganglion neurons and have been involved in persistent somatic hyperalgesic responses associated with inflammation. We assessed the role of Na_v1.9 channels on acute colonic inflammation-induced visceral hypersensitivity in conscious mice, using Na_v1.9 knockout (KO) mice. Colorectal distension (CRD)-induced visceral pain was assessed in conscious wild-type and Na_v1.9 KO mice (C57Bl/6 background). The mechanical activity of the abdominal muscles during isobaric colorectal distension was used as a measure of visceral pain. Acute colonic inflammation was induced by intracolonic administration of the toll-like receptor (TLR) 7 activator, R-848 (40 μg/animal). CRD was performed 5 h later, thereafter animals were euthanized and the colonic content of inflammatory mediators assessed. Normal pain responses were similar in Na_v1.9 KO and wild-type mice. In wild-type mice, R-848 administration increased the response to phasic CRD by 62% compared with vehicle-treated animals (vehicle: 0.16 ± 0.04, R-848: 0.26 ± 0.03, n = 6–7, P < 0.05). However, in Na_v1.9 KO mice, intracolonic R-848 did not affect the response to CRD (0.11 ± 0.02, n = 7) compared to animals treated with vehicle (0.17 ± 0.03, n = 5; P > 0.05). After R-848 administration, the colonic content of pro-inflammatory cytokines was increased in similar proportion in wild type and Na_v1.9 KO mice, suggesting the presence of a similar acute inflammatory reaction in both groups of animals. These results suggest that Na_v1.9 channels do not significantly contribute to normal visceral pain responses to acute colonic mechanical stimulation but may be important for the development of inflammation-related acute visceral hyperalgesic responses.     

Maternal diet rich in saturated fats has deleterious effects on plasma lipids of mice

BACKGROUND AND OBJECTIVES: High dietary fat intake has been reported to cause an alteration in lipid metabolism that is associated with an increased risk of cardiovascular disease. In the present study, an animal model was used to evaluate the effects of feeding diets rich in different fatty acids to mothers during pregnancy and lactation, and the effects of the maternal diet on parameters of lipid metabolism in adult offspring. The interaction between the offspring's own diet and the programming due to the maternal diet was also evaluated. METHODS: Female C57BL/6 mice were fed a high-fat diet (20% fat [weight to weight]) rich in either saturated fatty acids (SFA) or polyunsaturated fatty acids (PUFA) for two weeks before mating, during pregnancy and until weaning. The offspring were divided into two groups; each group was fed a high-fat diet enriched in either SFA or PUFA for eight weeks after weaning. The groups were designated as SFA/SFA (diet of the mother/diet of the offspring), SFA/PUFA, PUFA/PUFA and PUFA/SFA. Blood and tissues were collected at the end of the eight-week feeding period after an overnight fast. RESULTS: The plasma total cholesterol and low density lipoprotein cholesterol concentrations were significantly higher in the SFA/SFA group than in all other groups, whereas the PUFA/PUFA group had the lowest total cholesterol and low density lipoprotein cholesterol concentrations. Plasma high density lipoprotein cholesterol concentrations were significantly higher in the PUFA/SFA group than in the PUFA/PUFA and SFA/PUFA groups, whereas plasma triglyceride concentrations were not different among the groups. CONCLUSIONS: The data suggest that high maternal dietary fat intake during pregnancy affects lipid metabolism in the adult offspring. However, it appears that the offspring's own diet is also important in maintaining the regulation of lipid metabolism.     

Effects of subarachnoid lidocaine, meperidine and fentanyl on somatosensory and motor evoked responses in awake humans

Although the effects of local anaesthetics (LA) on motor and sensory transmission in the spinal cord have been described, the effects of opioids are controversial. Our aim was to evaluate the action of clinically relevant doses of subarachnoid (SA) meperidine (MP) and fentanyl (FN), on somatosensory (SSEP) and cortical motor evoked responses (CMER) in awake subjects. Thirty ASA I-II patients scheduled for infra umbilical surgery received SA (N = 10/group): 1 mg/kg lidocaine (LD), 1 mg/kg MP or 25 μg FN. SSEP elicited by stimulation of the posterior tibial nerve at the ankle, and cortical motor evoked response at rest (r-CMER) and during facilitation (f-CMER) were obtained prior and 30 min after treatment. Conduction at the proximal segment of the motor nerve (F-wave) was evaluated by stimulation ot the posterior tibial nerve at the popliteal fossa. Motor/sensory block and side effects were clinically assessed.
LD completely abolished SSEP and CMER. At the same dose, MP abolished SSEP in 40% of the patients, while r-CMER and f-CMER were absent in 70% and 30%, respectively; in addition, the F-wave was absent in 50% of the patients. Fentanyl induced small changes in the latencies of SSEP and F-wave; however, a 28% decrease in the amplitude of the f-CMER (P<0.05) was observed. Pruritus was present in 60% of patients in the FN group (P<0.006).
Our results show that while LD and MP block sensory and motor conduction at the spinal roots, FN seems to decrease the excitability of the spinal interneurons in the corticospinal tract.     

Heart rate,metabolic and hormonal responses to maximal psycho-emotional and physical stress in motor car racing drivers

Summary Motor car racing is representative of concentrative sporting activities, as well as instructive for mental-concentrative and psycho-emotional stress, which predominates with lower intensity, but longer duration in occupational work of today. A group of 20 car racing drivers was investigated both during car races (Formula Ford and Renault-5-Cup) and during progressive bicycle ergometry in the laboratory. Heart rate during car racing reached a mean level of 174.3 ± 14.1 min^–1 (mean ± SD), corresponding to 90% of the maximal heart rate achieved at the end of exhaustive ergometry (n = 12). Catecholamine excretion in urine (adrenaline + noradrenaline) on average was 252.3 ± 77.9 ng min^–1 during car racing and 121.9 ± 37.3 ng min^–1 during exhaustive ergometry (n = 10). Most of the other metabolic parameters determined in blood (lactate, glucose, FFA = free fatty acids, plasma protein, insulin, HGH = human growth hormone) also showed significant differences between car racing and bicycle ergometry (n = 20). Therefore it is possible to distinguish between psychical and physical strain and the quantify their specific level. Especially blood lactate can be considered as a metabolic indicator of physical strain and FFA of psycho-emotional strain. Furthermore, significant negative correlations could be found between heart rate, FFA level, and catecholamine excretion during car racing and some measures of physical fitness determined on the bicycle ergometer (n = 12 or 10). This suggests a reduced cardiocirculatory and metabolic strain reaction in response to psychical stress situations with increased fitness. Moreover, HDL (high density lipoprotein) was found increased and oral glucose tolerance test was improved with elevated physical fitness (n = 20, respectively 16). From the results of this study it can be concluded that physical activity counteracts atherosclerosis and CHD (coronary heart disease), which are promoted by psycho-emotional and psycho-social stress.     

Letter to the editor: Chronicle for an orphan trait: comment on Hofer, Shair, Masmela, & Brunelli, "Developmental effects of selective breeding for an infantile trait: the rat pup ultrasonic isolation call".

Hofer, Brunelli, Shair, and Masmela (2001) examined several behavioral and physiological measures in low, high, and unselected lines obtained from a divergent selection for ultrasound production (USP) in young rats. Although the response to selection was clear-cut, few correlated responses appeared. This surprising result could be explained by two reasons. USP has polygenic correlates in this population, and most of the chromosomal regions that are linked with these measures only contribute to a small part of the genetic variance. Therefore, correlated responses to selection might exist, but the common genetic variance between the trait under selection and the indirectly selected trait is too small to be detected by a selective breeding strategy.