bluuebunny/crossref_metadata_2025 huggingface dataset:
Desensitization of the peristaltic reflex induced by mucosal stimulation with the selective 5-HT4agonist tegaserod
Authors: Grider John R.
Published: October 2005

The intestinal peristaltic reflex induced by mucosal stimulation is mediated by mucosal release of serotonin (5-HT), which acts on 5-HT4receptors located on CGRP-containing afferent nerve terminals. Exposure of the colonic mucosa to the 5-HT4receptor agonist tegaserod in the range of 1 nM to 10 μM elicits a peristaltic reflex and stimulates colonic propulsion. The present study was designed to identify the 5-HT4receptor subtype mediating the reflex and determine whether functionally effective concentrations of tegaserod desensitize the reflex induced by mucosal stimulation. Exposure of rat colonic mucosa to tegaserod in the range of 5 nM to 5 μM for 5 or 10 min caused rapid time- and concentration-dependent desensitization of the peristaltic reflex induced by mucosal stroking, consistent with the operation of a rapidly desensitizing 5-HT4breceptor subtype. Desensitization was accompanied by a decrease in CGRP release. The rate of recovery of peristaltic response depended on the desensitizing concentration of tegaserod: ascending contraction and descending relaxation recovered within 15 min after 5–50 nM tegaserod, 30 min after 0.5 μM, and 60 min after 5 μM. Neither CGRP release nor the peristaltic reflex induced by muscle stretch was affected by 5-HT4receptor desensitization, providing further evidence that 5-HT does not mediate the reflex induced by muscle stretch. These results suggest in cases of increased 5-HT availability or prolonged exposure, such as colitis, that it is likely the peristaltic reflex will be blunted.
Hepatocyte nuclear factor-1α is required for expression but dispensable for histone acetylation of the lactase-phlorizin hydrolase gene in vivo
Authors: Bosse Tjalling , van Wering Herbert M. , Gielen Marieke , Dowling Lauren N. , Fialkovich John J. , Piaseckyj Christina M. , Gonzalez Frank J. , Akiyama Taro E. , Montgomery Robert K. , Grand Richard J. , Krasinski Stephen D.
Published: October 2005

Hepatocyte nuclear factor-1α (HNF-1α) is a modified homeodomain-containing transcription factor that has been implicated in the regulation of intestinal genes. To define the importance and underlying mechanism of HNF-1α for the regulation of intestinal gene expression in vivo, we analyzed the expression of the intestinal differentiation markers and putative HNF-1α targets lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) in hnf1α null mice. We found that in adult jejunum, LPH mRNA in hnf1α−/−mice was reduced 95% compared with wild-type controls ( P < 0.01, n = 4), whereas SI mRNA was virtually identical to that in wild-type mice. Furthermore, SI mRNA abundance was unchanged in the absence of HNF-1α along the length of the adult mouse small intestine as well as in newborn jejunum. We found that HNF-1α occupies the promoters of both the LPH and SI genes in vivo. However, in contrast to liver and pancreas, where HNF-1α regulates target genes by recruitment of histone acetyl transferase activity to the promoter, the histone acetylation state of the LPH and SI promoters was not affected by the presence or absence of HNF-1α. Finally, we showed that a subset of hypothesized intestinal target genes is regulated by HNF-1α in vivo and that this regulation occurs in a defined tissue-specific and developmental context. These data indicate that HNF-1α is an activator of a subset of intestinal genes and induces these genes through an alternative mechanism in which it is dispensable for chromatin remodeling.
Mechanisms of mutual functional interactions between HNF-4α and HNF-1α revealed by mutations that cause maturity onset diabetes of the young
Authors: Rowley Christopher W. , Staloch Lora J. , Divine Joyce K. , McCaul Sean P. , Simon Theodore C.
Published: October 2005

Hepatic nuclear factor (HNF)-4α and HNF-1α are key endodermal transcriptional regulators that physically and functionally interact. HNF-4α and HNF-1α cooperatively activate genes with binding sites for both factors, whereas suppressive interactions occur at regulatory sequences with a binding site for only one factor. The liver fatty acid binding protein gene ( Fabp1) has binding sites for both factors, and chromatin precipitation assays were utilized to demonstrate that HNF-4α increased HNF-1α Fabp1 promoter occupancy during cooperative transcriptional activation. The HNF4 P2 promoter contains a HNF-1 but not HNF-4 binding site, and HNF-4α suppressed HNF-1α HNF4 P2 activation and decreased promoter HNF-1α occupancy. The apolipoprotein C III ( APOC3) promoter contains a HNF-4 but not HNF-1 binding site, and HNF-1α suppressed HNF-4α APOC3 activation and decreased HNF-4α promoter occupancy. Maturity onset diabetes of the young (MODY) as well as defects in hepatic lipid metabolism result from mutations in either HNF-4α or HNF-1α. We found that MODY missense mutant R127W HNF-4α retained wild-type individual Fabp1 activation and bound to HNF-1α better than wild-type HNF-4α, yet did not cooperate with HNF-1α or increase HNF-1α Fabp1 promoter occupancy. The R127W mutant was also defective in both suppressing HNF-1α activation of HNF4 P2 and decreasing HNF-1α promoter occupancy. The HNF-1α R131Q MODY mutant also retained wild-type Fabp1 activation and bound to HNF-4α as well as the wild type but was defective in both suppressing HNF-4α APOC3 activation and decreasing HNF-4α promoter occupancy. These results suggest HNF-1α-HNF-4α functional interactions are accomplished by regulating factor promoter occupancy and that defective factor-factor interactions may contribute to the MODY phenotype.
Roles of adrenomedullin 2 in regulating the cardiovascular and sympathetic nervous systems in conscious rats
Authors: Fujisawa Yoshihide , Nagai Yukiko , Miyatake Akira , Miura Katsuyuki , Shokoji Takatomi , Nishiyama Akira , Kimura Shoji , Abe Youichi
Published: October 2005

Recently, a new member of the calcitonin gene-related peptide (CGRP) family, adrenomedullin 2 (AM2) or intermedin (IMD), was identified. AM2/IMD has been shown to have a vasodilator effect in mice and rats and an effect on urine formation in rats. In the present study, we investigated the effects of intravenously infused rat AM2 (rAM2) on blood pressure (BP), heart rate (HR), renal sympathetic nerve activity (RSNA), and renal blood flow (RBF) in conscious unrestrained rats relative to the effects of rat adrenomedullin (rAM) and proadrenomedullin NH2-terminal 20 peptide (rPAMP). Intravenous infusion of rAM2 (5 nmol/kg) significantly decreased BP and increased HR, RSNA, and RBF. These hypotensive and sympathoexcitatory effects diminished after 20 min, and HR returned to control levels 30 min after cessation of the infusion. In contrast, a significant increase in RBF was still evident 60 min after cessation of the peptide infusion. The duration of BP, HR, and RSNA responses was longer with rAM (5 nmol/kg) than with rAM2 infusion, whereas the increases in RBF induced by rAM2 and rAM were similar in their amplitude and duration. Infusion of rPAMP (200 nmol/kg) increased HR and RSNA but had no effect on RBF. Baroreceptor denervation suppressed, but did not diminish, the increases in HR and RSNA to rAM2. These findings indicate that the physiological roles of rAM2 and rAM are similar and that rAM2 also has a long-lasting vasodilator action on the renal vascular bed.
Impaired potency of bone marrow mononuclear cells for inducing therapeutic angiogenesis in obese diabetic rats
Authors: Li Tao-Sheng , Furutani Akira , Takahashi Masaya , Ohshima Mako , Qin Shu-Lan , Kobayashi Toshiro , Ito Hiroshi , Hamano Kimikazu
Published: October 2005

Using Zucker fatty rats, a strain characterized by diabetes and hyperlipidemia, we investigated the diabetes- and hyperlipidemia-related impairment of bone marrow mononuclear cells (BMCs) for inducing therapeutic angiogenesis. BMCs from Zucker fatty and normal Zucker lean rats were collected and cultured. Although the characterization and cell survival of BMCs did not differ, the VEGF production, endothelial differentiation, and endothelial cell colony-forming potential of BMCs from Zucker fatty rats were significantly lower than those of BMCs from lean rats. By using an ischemic hindlimb model, we found that the native recovery of induced limb ischemia in the Zucker fatty rats was also significantly worse than that in the lean rats. Furthermore, the expression of 5-hydroxytryptamine (5-HT2A) receptors was obviously higher in the Zucker fatty rats than that in the lean rats and was enhanced after limb ischemia. Although the therapeutic potency was lower than with the implantation of BMCs from normal lean rats, the implantation of BMCs from fatty rats could also induce angiogenesis and increase blood flow significantly in the ischemic hindlimbs of Zucker fatty rats. Furthermore, the blood flow in the ischemic hindlimbs was increased by the administration of sarpogrelate, a selective 5-HT2A-receptor antagonist. Our results clearly show diabetes- and hyperlipidemia-related dysfunction and impaired potency for inducing angiogenesis of BMCs. However, the implantation of autologous BMCs into ischemic limbs of diabetic and hyperlipidemic rats has induced therapeutic angiogenesis effectively, and blood flow would be enhanced by the administration of a 5-HT2A-receptor antagonist.
Sex and estrous cycle differences in the behavioral effects of high-strength static magnetic fields: role of ovarian steroids
Authors: Cason Angie M. , DenBleyker Megan , Ferrence Kimberly , Smith James C. , Houpt Thomas A.
Published: October 2005

Advances in magnetic resonance imaging are driving the development of higher-resolution machines equipped with high-strength static magnetic fields (MFs). The behavioral effects of high-strength MFs are largely uncharacterized, although in male rats, exposure to 7 T or above induces locomotor circling and leads to a conditioned taste avoidance (CTA) if paired with a novel taste. Here, the effects of MFs on male and female rats were compared to determine whether there are sex differences in behavioral responses and whether these can be explained by ovarian steroid status. Rats were given 10-min access to a novel saccharin solution and then restrained within a 14-T magnet for 30 min. Locomotor activity after exposure was scored for circling and rearing. CTA extinction was measured with two-bottle preference tests. In experiment 1, males were compared with females across the estrous cycle after a single MF exposure. Females circled more and acquired a more persistent CTA than males; circling was highest on the day of estrus. In experiment 2, the effects of three MF exposures were compared among intact rats, ovariectomized females, and ovariectomized females with steroid replacement. Compared with intact rats, ovariectomy increased circling; estrogen replacement blocked the increase. Males acquired a stronger initial CTA but extinguished faster than intact or ovariectomized females. Thus the locomotor circling induced by MF exposure was increased in females and modulated by ovarian steroids across the estrous cycle and by hormone replacement. Furthermore, female rats acquired a more persistent CTA than male rats, which was not dependent on estrous phase or endogenous ovarian steroids.
Membrane proteins involved in potassium shifts during muscle activity and fatigue
Authors: Kristensen Michael , Hansen Thomas , Juel Carsten
Published: October 2005

Muscle activity is associated with potassium displacements, which may cause fatigue. It was reported previously that the density of the large-conductance Ca2+-dependent K+ (BKCa) channel is higher in the T tubule membrane than in the sarcolemmal membrane and that the opposite is the case for the ATP-sensitive K+ (KATP) channel. In the present experiments, we investigated the subcellular localizations of the strong inward rectifier 2.1 K+ (Kir2.1) channel and the Na+-K+-2Cl− (NKCC)1 cotransporter with Western blot analysis of different muscle fractions. Furthermore, muscle function was studied while trying to manipulate the opening probability or transport capacity of these proteins during electrical stimulation of isolated soleus muscles. All experiments were made with excised muscle from male Wistar rats. Kir2.1 channels were almost undetectable in the sarcolemmal membrane but present in the T tubule membrane, whereas NKCC1 cotransporters were present in the sarcolemmal membrane. For muscles incubated in a buffer containing pinacidil, NS1619, Ba2+, or bumetanide, there was a faster reduction in peak force ( P < 0.05). Furthermore, bumetanide incubation reduced the peak force at the onset of electrical stimulation ( P < 0.05). Thus the effects on muscle force indicate that these drugs can affect K+-transporting proteins and thereby influence K+ accumulation, especially in the T tubules, suggesting that KATP and BKCa channels are responsible for K+ release and decrease in force during repeated muscle contractions, whereas Kir2.1 and NKCC1 may have a role in K+ reuptake.
Postnatal constriction, ATP depletion, and cell death in the mature and immature ductus arteriosus
Authors: Levin Max , McCurnin Don , Seidner Steven R. , Yoder Bradley , Waleh Nahid , Goldbarg Seth , Roman Christine , Liu Bao Mei , Borén Jan , Clyman Ronald I.
Published: October 2005

After birth, constriction of the full-term ductus arteriosus induces oxygen, glucose and ATP depletion, cell death, and anatomic remodeling of the ductus wall. The immature ductus frequently fails to develop the same degree of constriction or anatomic remodeling after birth. In addition, the immature ductus loses its ability to respond to vasoconstrictive agents, like oxygen or indomethacin, with increasing postnatal age. We examined the effects of premature delivery and postnatal constriction on the immature baboon ductus arteriosus. By 6 days after birth, surrogate markers of hypoxia (HIF1α/VEGF mRNA) and cell death [dUTP nick-end labeling (TUNEL)-staining] increased, while glucose and ATP concentrations (bioluminescence imaging) decreased in the immature ductus. TUNEL-staining was significantly related to the degree of glucose and ATP depletion. Glucose and ATP depletion were directly related to the degree of ductus constriction; while TUNEL-staining was logarithmically related to the degree of ductus constriction. Extensive cell death (>15% TUNEL-positive cells) occurred only when there was no Doppler flow through the ductus lumen. In contrast, HIF1α/VEGF expression and ATP concentrations were significantly altered even when the immature ductus remained open after birth. Decreased ATP concentrations produced decreased oxygen-induced contractile responses in the immature ductus. We hypothesize that ATP depletion in the persistently patent immature newborn ductus is insufficient to induce cell death and remodeling but sufficient to decrease its ability to constrict after birth. This may explain its decreasing contractile response to oxygen, indomethacin, and other contractile agents with increasing postnatal age.
Noninvasive in vivo monitoring of methemoglobin formation and reduction with broadband diffuse optical spectroscopy
Authors: Lee Jangwoen , El-Abaddi Naglaa , Duke Andrew , Cerussi Albert E. , Brenner Matthew , Tromberg Bruce J.
Published: October 2005

We present noninvasive, quantitative in vivo measurements of methemoglobin formation and reduction in a rabbit model using broadband diffuse optical spectroscopy (DOS). Broadband DOS combines multifrequency frequency-domain photon migration (FDPM) with time-independent near infrared (NIR) spectroscopy to quantitatively measure bulk tissue absorption and scattering spectra between 600 nm and 1,000 nm. Tissue concentrations (denoted by brackets) of methemoglobin ([MetHb]), deoxyhemoglobin ([Hb-R]), and oxyhemoglobin ([HbO2]) were determined from absorption spectra acquired in “real time” during nitrite infusions in nine pathogen-free New Zealand White rabbits. As little as 30 nM [MetHb] changes were detected for levels of [MetHb] that ranged from 0.80 to 5.72 μM, representing 2.2 to 14.9% of the total hemoglobin content (%MetHb). These values agreed well with on-site ex vivo cooximetry data ( r2= 0.902, P < 0.0001, n = 4). The reduction of MetHb to functional hemoglobins was also carried out with intravenous injections of methylene blue (MB). As little as 10 nM changes in [MB] were detectable at levels of up to 150 nM in tissue. Our results demonstrate, for the first time, the ability of broadband DOS to noninvasively quantify real-time changes in [MetHb] and four additional chromophore concentrations ([Hb-R], [HbO2], [H2O], and [MB]) despite significant overlapping spectral features. These techniques are expected to be useful in evaluating dynamics of drug delivery and therapeutic efficacy in blood chemistry, human, and preclinical animal models.
Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes
Authors: Spiegel Karine , Knutson Kristen , Leproult Rachel , Tasali Esra , Cauter Eve Van
Published: October 2005

Chronic sleep loss as a consequence of voluntary bedtime restriction is an endemic condition in modern society. Although sleep exerts marked modulatory effects on glucose metabolism, and molecular mechanisms for the interaction between sleeping and feeding have been documented, the potential impact of recurrent sleep curtailment on the risk for diabetes and obesity has only recently been investigated. In laboratory studies of healthy young adults submitted to recurrent partial sleep restriction, marked alterations in glucose metabolism including decreased glucose tolerance and insulin sensitivity have been demonstrated. The neuroendocrine regulation of appetite was also affected as the levels of the anorexigenic hormone leptin were decreased, whereas the levels of the orexigenic factor ghrelin were increased. Importantly, these neuroendocrine abnormalities were correlated with increased hunger and appetite, which may lead to overeating and weight gain. Consistent with these laboratory findings, a growing body of epidemiological evidence supports an association between short sleep duration and the risk for obesity and diabetes. Chronic sleep loss may also be the consequence of pathological conditions such as sleep-disordered breathing. In this increasingly prevalent syndrome, a feedforward cascade of negative events generated by sleep loss, sleep fragmentation, and hypoxia are likely to exacerbate the severity of metabolic disturbances. In conclusion, chronic sleep loss, behavioral or sleep disorder related, may represent a novel risk factor for weight gain, insulin resistance, and Type 2 diabetes.
Inverse relationship between PGC-1α protein expression and triacylglycerol accumulation in rodent skeletal muscle
Authors: Benton Carley R. , Han Xiao-Xia , Febbraio Maria , Graham Terry E. , Bonen Arend
Published: October 2005

PGC-1α is a key regulator of tissue metabolism, including skeletal muscle. Because it has been shown that PGC-1α alters the capacity for lipid metabolism, it is possible that PGC-1α expression is regulated by the intramuscular lipid milieu. Therefore, we have examined the relationship between PGC-1α protein expression and the intramuscular fatty acid accumulation in hindlimb muscles of animals in which the capacity for fatty acid accumulation in muscle is increased (Zucker obese rat) or reduced [FAT/CD36 null (KO) mice]. Rates of palmitate incorporation into triacylglycerols were determined in perfused red (RG) and white gastrocnemius (WG) muscles of lean and obese Zucker rats and in perfused RG and WG muscles of FAT/CD36 KO and wild-type (WT) mice. In obese Zucker rats, the rate of palmitate incorporation into triacylglycerol depots in RG and WG muscles were 28 and 24% greater than in lean rats ( P < 0.05). In FAT/CD36 KO mice, the rates of palmitate incorporation into triacylglycerol depots were lower in RG (−50%) and WG muscle (−24%) compared with the respective muscles in WT mice ( P < 0.05). In the obese animals, PGC-1α protein content was reduced in both RG (−13%) and WG muscles (−15%) ( P < 0.05). In FAT/CD36 KO mice, PGC-1α protein content was upregulated in both RG (+32%, P < 0.05) and WG muscles (+50%, P < 0.05). In conclusion, from studies in these two animal models, it appears that PGC-1α protein expression is inversely related to components of intramuscular lipid metabolism, because 1) PGC-1α protein expression is downregulated when triacylglycerol synthesis rates, an index of intramuscular lipid metabolism, are increased, and 2) PGC-1α protein expression is upregulated when triacylglycerol synthesis rates are reduced. Therefore, we speculate that the intramuscular lipid sensing may be involved in regulating the protein expression of PGC-1α in skeletal muscle.
Regulation of HSP25 expression and phosphorylation in functionally overloaded rat plantaris and soleus muscles
Authors: Huey Kimberly A.
Published: October 2005

Functional overload (FO) is a powerful inducer of muscle hypertrophy and both oxidative and mechanical stress in muscle fibers. Heat shock protein 25 (HSP25) may protect against both of these stressors, and its expression can be regulated by changes in muscle loading and activation. The primary purpose of the present study was to test the hypothesis that chronic FO increases HSP25 expression and phosphorylation (pHSP25) in hypertrophying rat hindlimb muscle. HSP25 and pHSP25 levels were quantified in soluble and insoluble fractions of the soleus and plantaris to determine whether 3 or 7 days of FO increase translocation of HSP25 and/or pHSP25 to the insoluble fraction. p38 protein and phosphorylation (p-p38) was measured to determine its association with changes in pHSP25. HSP25 mRNA showed time-dependent increases in both the soleus and plantaris with FO. Three or seven days of FO increased HSP25 and pHSP25 in the soluble fraction in both muscles, with a greater response in the plantaris. In the insoluble fraction, HSP25 was increased after 3 or 7 days in both muscles, whereas pHSP25 was only increased in the 7-day plantaris. p38 and p-p38 increased in the plantaris at both time points. In the soleus, p-p38 only increased after 7 days. These results show that FO is associated with changes in HSP25 expression and phosphorylation and suggest its role in the remodeling that occurs during muscle hypertrophy. Increases in HSP25 in the insoluble fraction suggest that it may help to stabilize actin and/or other cytoskeletal proteins during the stress of muscle remodeling.
Antimicrobial Activity of a Series of 1-Alkyl-2-(4-Pyridyl)Pyridinium Bromides against Gram-Positive and Gram-Negative Bacteria
Authors: Denny B.J. , Novotny L. , West P.W.J. , Blesova M. , Zamocka J.
Published: October 2005

Objective: To test a series of 1-alkyl-2-(4-pyridyl)pyridinium bromides with alkyl chains containing between 9 and 16 carbons against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Stenotrophomonas maltophilia, Acinetobacter baumannii and Pseudomonas aeruginosa) bacteria. Materials and Methods: Chemical synthesis was based on the reaction of 2,4′-bipyridyl with alkyl bromide. Antimicrobial activity of the bipyridyls was measured by growing bacterial cultures on Mueller-Hinton agar in the presence and absence of inhibitors. Results:The compounds were most active against S. aureus. The most active compounds had alkyl chain lengths of between 11 and 16 carbons. Methicillin-sensitive S. aureus was more susceptible to the inhibitors than methicillin-resistant S. aureus (MRSA). Two subclasses of MRSA existed which differed in their susceptibility to the inhibitors. The susceptibility of MRSA strains to the compounds was increased in the presence of the efflux pump inhibitor reserpine. The activity of the compounds against Gram-negative organisms was increased when the membrane-permeabilizing agent sodium citrate was introduced. Critical micelle concentrations of the compounds were much higher than minimum inhibitory concentrations of the inhibitors. Conclusion: The mechanism of action of the compounds may involve perturbing bacterial membranes. The resistance of some MRSA strains to the compounds may be related to efflux pumps.
Prevalence and Severity of Malocclusion in Adolescent Kuwaitis
Authors: Behbehani Faraj , Årtun Jon , Al-Jame Badreia , Kerosuo Heidi
Published: October 2005

Objectives: Our aim was to evaluate prevalence and severity of malocclusion in an adolescent Kuwaiti population. Subjects and Methods: Using a stratified cluster sampling method and excluding non-Kuwaitis, subjects with mesial migration and/or loss of first molars, and subjects with orthodontic treatment experience without availability of initial study models, we examined 1,299 Kuwaitis (674 boys and 625 girls) of mean age 13.2 ± 0.4 years in a regular well lit classroom. We scored molar and canine relationship, overjet, overbite, anterior and posterior cross bite as well as spacing and irregularity of the incisors using gloves, mirrors, rulers, and spatulas. Results: Fourteen, 15, and 71% met the criteria for almost ideal, mild, and moderate to severe malocclusion, respectively. Of the 86% with malocclusion, occurrence of class 1, half step class 2, full step class 2, half step class 3, and full step class 3 was 57.8, 24.9, 6.3, 8.8, and 2.2% for the first molars, and 36.1, 50.0, 6.2, 5.4, and 2.3% for the canines, respectively. Incisor malalignment was the most prevalent malocclusion trait (73.2%). Overjet ≧9.5 mm occurred in less than 1.5%, open bite in less than 3.5%, deep bite with gingival contact in less than 2.0%, complete posterior cross bite in less than 1.5%, and complete anterior crossbite in less than 2.0%. Median diastema was present in about 2/3 of the cases with maxillary anterior spacing as opposed to only about 1/3 of those with mandibular spacing. Conclusion: Our findings suggest that more than 70% of young adolescent Kuwaitis have moderate to severe malocclusion, with incisor malalignment as the most prevalent malocclusion trait.
Spectrum and Antibiotic Resistance of Uropathogens Isolated from Hospital and Community Patients with Urinary Tract Infections in Two Large Hospitals in Kuwait
Authors: Al Sweih Noura , Jamal Wafaa , Rotimi V.O.
Published: October 2005

Objectives: To determine the spectrum of microbial etiology and antibiotic resistance pattern of the uropathogens that cause urinary tract infections in 2 large teaching hospitals in Kuwait over a period of 1 year. Materials and Methods: The Vitek identification card system was used to identify the uropathogens. Susceptibility of the isolates against 18 antibiotics was performed by the microbroth dilution method using the Vitek automated system. In addition, gram-positive bacteria were tested in parallel by the disk diffusion technique. Results: The six overall most common isolates were: Escherichia coli, accounting for 47% of isolates in both hospitals, followed by Candida spp. (10.8%), Klebsiella pneumoniae (9.6%), Streptococcus agalactiae (GBS; 9.5%), Enterococcusfaecalis (4.2%) and Pseudomonas aeruginosa (4.1%). Amikacin provided the widest coverage amongst all the antibiotics tested followed by ciprofloxacin, gentamicin and piperacillin-tazobactam. For the gram-negatives, high resistance (26–63%) to the β-lactam antibiotics was noted, especially to ampicillin, amoxicillin-clavulanic acid, cephalothin and cefuroxime. Resistance to trimethoprim-sulfamethoxazole was also high. None of the enterococci was resistant to the glycopeptides, but 38–60% of the Staphylococcus haemolyticus were resistant to vancomycin or teicoplanin. Conclusion: These data show the high level of antimicrobial resistance amongst the uropathogens causing urinary tract infection in the two hospitals studied.
Incidence of Bloodstream Infections in a Speciality Hospital in Kuwait: 8-Year Experience
Authors: Dimitrov T.S. , Panigrahi D. , Emara M. , Al-Nakkas A. , Awni F. , Passadilla R.
Published: October 2005

Objectives: To determine the frequency of isolation and antibiotic-susceptibility patterns of clinically significant bacterial pathogens isolated from blood. Materials and Methods: The study was conducted over a period of 8 years (1995–2002) at Infectious Diseases Hospital (IDH), Kuwait. Demographic and clinical data were obtained from medical records. 18,535 blood cultures were analyzed. Disk diffusion method was used to perform antibiotic-susceptibility testing. Minimum inhibitory concentrations of 9 antimicrobials were determined using E-test. Double disk (potentiation) test and E-test ESBL strips were used to detect the production of extended-spectrum beta-lactamases (ESBLs). Results:Salmonella spp. and Brucella spp. were predominant blood isolates, and represented 60.6 and 30.0% of all clinically significant episodes of bloodstream infections, respectively. Among the Salmonella, Salmonella enterica serotypes typhi and paratyphi A were most frequently isolated. The percentage of multidrug resistance (MDR) among them varied from 22 to 51%. A high percentage (40%) of MDR S. enterica serotypes typhi and paratyphi A also showed reduced susceptibility to ceftriaxone and ciprofloxacin. Conclusion: During the study period, Salmonella spp. and Brucella spp. were predominant blood isolates. MDR S. enterica serotypes typhi and paratyphi A, with reduced susceptibility to ceftriaxone and ciprofloxacin, are among the most frequent causes of bloodstream infections in IDH, suggesting the need to monitor their susceptibility.
Modulation of the Transforming Growth Factor β1 by Vitamin E in Early Nephropathy
Authors: Cojocel C. , Al-Maghrebi M. , Thomson M.S. , Rawoot P. , Raghupathy R.
Published: October 2005

Objective: The aim of this study was to investigate the pharmacological activity of an antioxidant, α-tocopherol (vitamin E, VE) in streptozotocin-induced diabetic rats and study its role in modulating the transforming growth factor β1 (TGF-β1). Methods: Male Sprague-Dawley rats were treated with streptozotocin to induce diabetes. VE and/or insulin (INS) were administered daily during treatment periods of 3, 5, 7 and 10 days. Plasma glucose and fructosamine were measured in diabetic rats at the end of each treatment period. Samples of plasma, urine and renal cortex were analyzed for changes in protein and lysozyme excretion, reduced glutathione and malondialdehyde formation. TGF-β1 was determined by ELISA and expression of TGF-β1 mRNA was investigated by RT-PCR and Northern blot analysis. Results: Diabetes-induced glycemic stress was suppressed by INS, VE or a combination of INS and VE. Diabetes-induced increases of glucose, protein and lysozyme excretion were markedly depressed after 10-day treatment with INS, VE and the combination of INS and VE. Decreased glutathione content in the renal cortex of diabetic rats recovered towards control values, especially after 10-day treatment. Malondialdehyde content increased in diabetic rats and was reduced towards control value following 7- and 10-day treatments. Treatment of diabetic rats with INS, VE or the combination of INS and VE decreased elevated TGF-β1 in plasma, decreased excretion of TGF-β1 in urine, and decreased renal cortex TGF-β1 mRNA levels. Conclusions: Diabetes-induced overexpression of TGF-β1 mRNA was suppressed by VE and INS after 5-, 7- and 10-day treatments. The results obtained with the antioxidant VE suggest that oxidative stress is involved in the development of diabetic nephropathy. Therefore, VE treatment may be effective in early stages of diabetic nephropathy to decrease or prevent pathological complications.
In vitro Activities of Various Antimicrobials against Brucella melitensis Strains in the Aegean Region in Turkey
Authors: Yamazhan Tansu , Aydemir Şöhret , Tünger Alper , Serter Demir , Gökengin Deniz
Published: October 2005

Objective: To study in vitro activities of three quinolones (ciprofloxacin, levofloxacin, moxifloxacin), four macrolides (erythromycin, dirithromycin, azithromycin, clarithromycin) and doxycycline against 44 clinical isolates of Brucella melitensis. Materials and Methods: Forty-four B. melitensis strains were isolated from blood cultures of adult patients with acute brucellosis who were hospitalized in the clinical ward of the Department of Clinical Microbiology and Infectious Diseases. The minimum inhibitory concentrations (MICs) of the tested antimicrobials were measured by the agar dilution method. MIC90 and MIC50 values were defined as the lowest concentration of the antibiotic at which 90 and 50% of the isolates were inhibited, respectively. Results: Doxycycline (MIC50: 0.25 µg/ml, MIC90: 0.50 µg/ml) had the lowest MIC in vitro against the B. melitensis strains. Among the quinolones, ciprofloxacin and levofloxacin had similar activities (MIC50: 0.5 µg/ml, MIC90: 2 µg/ml), whereas MIC of moxifloxacin (MIC50: 1 µg/ml, MIC90: 8 µg/ml) was higher than both antibiotics in this group. Clarithromycin and azithromycin were the most active macrolides (MIC50: 8 µg/ml and MIC90: 32 µg/ml), followed by erythromycin (MIC50: 16 µg/ml, MIC90: 32 µg/ml) and dirithromycin (MIC50: 64 µg/ml and MIC90: 64 µg/ml). Conclusion: The results indicate that the conventional agent doxycycline is more active than quinolones and macrolides against the B. melitensis in vitro.
An Evoked Potential Study of the Developmental Time Course of the Auditory Nerve and Brainstem in Children Using Cochlear Implants
Authors: Gordon Karen A. , Papsin Blake C. , Harrison Robert V.
Published: October 2005

Central auditory responses to electrical stimulation from a cochlear implant were studied in 75 pre-lingually deafened children and 11 adults. Electrically evoked auditory brainstem response (EABR) latencies significantly decreased with duration of cochlear implant use and were not significantly affected by the age at implant activation. Significant decreases in early latency waves and interwaves occurred within the first 1–2 months of implant use, whereas longer term changes (6–12 months) were found for eV and eIII-eV, which measure activity in the more rostral brainstem. Comparisons to acoustically evoked auditory brainstem response (ABR) in children with normal hearing suggested shorter interwave EABR latencies, reflecting either distinct neural generators or increased neural synchrony, but similar rates of change in the later latency eV and eIII-eV with time in sound. In sum, normal-like development of the rostral auditory brainstem is promoted by cochlear implant use in children of a wide range of ages.
Clinical Application of Dichotic Multiple-Stimulus Auditory Steady-State Responses in High-Risk Newborns and Young Children
Authors: Luts Heleen , Desloovere Christian , Wouters Jan
Published: October 2005

Experience with dichotic multiple-stimulus auditory steady-state responses (ASSRs) in clinical practice is described. ASSR thresholds were assessed in a sample of 60 high-risk newborns and young children between birth and 4 years of age. Amplitudes and signal-to-noise ratios (SNRs) of the ASSR were compared between normal-hearing infants and adults. Age-related changes within a group of infants younger than 3 months of age were investigated. A comparison was made between ASSR, the click-evoked auditory brainstem response and behavioral hearing thresholds in infants with a wide range of hearing threshold levels. Mean ASSR thresholds for normal-hearing infants at an average corrected age of 12 days were 42 ± 10, 35 ± 10, 32 ± 10 and 36 ± 9 dB SPL for 0.5, 1, 2 and 4 kHz, respectively. Compared to adults, these thresholds were elevated by on average 11 dB and SNRs were 1.7 times smaller. However, based on ASSRs, reasonably accurate estimations could be made of behavioral hearing thresholds obtained at a later age (median delay of 7 months). The predicted thresholds were in 61% of the cases within 10 dB of the corresponding behavioral thresholds, and in 83% of the cases within 15 dB. In less than 1 h, thresholds at four frequencies per ear could be obtained. The optimal age of testing is between 1 week and 3 months corrected age. The dichotic multiple-stimulus ASSR technique is a valuable extension of the clinical test battery for hearing-impaired children, as a follow-up diagnostic after the neonatal hearing screening.
Improved Music Perception with Explicit Pitch Coding in Cochlear Implants
Authors: Laneau Johan , Wouters Jan , Moonen Marc
Published: October 2005

Music perception and appraisal is very poor in cochlear implant (CI) subjects partly because (musical) pitch is inadequately transmitted by the current clinically used sound processors. A new sound processing scheme (F0mod) was designed to optimize pitch perception, and its performance for music and pitch perception was compared in four different experiments to that of the current clinically used sound processing scheme (ACE) in six Nucleus CI24 subjects. In the F0mod scheme, slowly varying channel envelopes are explicitly modulated sinusoidally at the fundamental frequency (F0) of the input signal, with 100% modulation depth and in phase across channels to maximize temporal envelope pitch cues. The results of the four experiments show that: (1) F0 discrimination of single-formant stimuli was not significantly different for the two schemes, (2) F0 discrimination of musical notes of five instruments was three times better with the F0mod scheme for F0 up to 250 Hz, (3) melody recognition of familiar Flemish songs (with all rhythm cues removed) was improved with the F0mod scheme, and (4) estimates of musical pitch intervals, obtained in a musically trained CI subject, matched more closely the presented intervals with the F0mod scheme. These results indicate that explicit F0 modulation of the channel envelopes improves music perception in CI subjects.
Cellular Localization of AMPA Type Glutamate Receptor Subunits in the Basal Ganglia of Pigeons (Columba livia)
Authors: Laverghetta Antonio V. , Toledo Claudio A.B. , Veenman C. Leo , Yamamoto Kei , Wang Hongbing , Reiner Anton
Published: October 2005

Corticostriatal and thalamostriatal projections utilize glutamate as a neurotransmitter in mammals and birds. The influence on striatum is mediated, in part, by ionotropic AMPA-type glutamate receptors, which are heteromers composed of GluR1–4 subunits. Although the cellular localization of AMPA-type subunits has been well characterized in mammalian basal ganglia, their localization in avian basal ganglia has not. We thus carried out light microscopic single- and double-label and electron microscopic single-label immunohistochemical studies of GluR1–4 distribution and cellular localization in pigeon basal ganglia. Single-label studies showed that the striatal neuropil is rich in GluR1, GluR2, and GluR2/3 immunolabeling, suggesting the localization of GluR1, GluR2 and/or GluR3 to the dendrites and spines of striatal projection neurons. Double-label studies and perikaryal size distribution determined from single-label material indicated that about 25% of enkephalinergic and 25% of substance P-containing striatal projection neuron perikarya contained GluR1, whereas GluR2 was present in about 75% of enkephalinergic neurons and all substance-P -containing neurons. The perikaryal size distribution for GluR2 compared to GluR2/3 suggested that enkephalinergic neurons might more commonly contain GluR3 than do substance P neurons. Parvalbuminergic and calretininergic striatal interneurons were rich in GluR1 and GluR4, a few cholinergic striatal interneurons possessed GluR2, but somatostatinergic striatal interneurons were devoid of all subunits. The projection neurons of globus pallidus all possessed GluR1, GluR2, GluR2/3 and GluR4 immunolabeling. Ultrastructural analysis of striatum revealed that GluR1 was preferentially localized to dendritic spines, whereas GluR2/3 was found in spines, dendrites, and perikarya. GluR2/3-rich spines were generally larger than GluR1 spines and more frequently possessed perforated post-synaptic densities. These results show that the diverse basal ganglia neuron types each display different combinations of AMPA subunit localization that shape their responses to excitatory input. For striatal projection neurons and parvalbuminergic interneurons, the combinations resemble those for the corresponding cell types in mammals, and thus their AMPA responses to glutamate are likely to be similar.
The Eye of the Laboratory Mouse Remains Anatomically Adapted for Natural Conditions
Authors: Shupe Jonathan M. , Kristan Deborah M. , Austad Steven N. , Stenkamp Deborah L.
Published: October 2005

Evolutionary effects of domestication have been demonstrated for several body systems, including the eye, and for several vertebrate species, including the mouse. Given the importance of the laboratory mouse to vision science, we wished to determine whether the anatomical and histological features of the eyes of laboratory mice are distinct from those of their naturally adapted, wild counterparts. We measured dimensions and masses of whole eyes and lenses from a wild population plus three inbred strains (C57BL/6J, NZB/BINJ, and DBA/1J) of the house house, Mus musculus, as well as wild and outbred laboratory-domesticated stock of the deer mouse, Peromyscus maniculatus. Histological preparations from these eyes were used to determine outer nuclear layer thickness, linear density of the ganglion cell layer, and for indirect immunofluorescence evaluation of cone opsin expression. For all of these traits, no statistically significant differences were found between any laboratory strain and its wild counterpart. The evolutionary effects of domestication of mice therefore do not include changes to the eye in any variable measured, supporting the continued use of this animal as a model for a naturally adapted visual system.
Increased Levels of Serum-Specific Immunoglobulin E to Staphylococcal Enterotoxin A and B in Patients with Allergic Rhinitis and Bronchial Asthma
Authors: Lee Jyh-Hong , Lin Yu-Tsan , Yang Yao-Hsu , Wang Li-Chieh , Chiang Bor-Luen
Published: October 2005

Background: The association between staphylococcal enterotoxins and atopic dermatitis (AD) is well characterized. We aim to evaluate the association between sensitization to staphylococcal enterotoxin A (SEA) and/or B (SEB) and the development of allergic airway disease. Methods: Two hundred and seventy-four patients were grouped into allergic rhinitis (AR) and/or bronchial asthma (BA) only, AD only and AR/BA+AD. The AR/BA only group was further divided into AR only, AR and airway hyperresponsiveness (AR+AHR) and BA. The allergen-specific and total immunoglobulin E (IgE) antibodies were determined by the CAP system. The associations of sensitization to SEA/SEB with allergic airway disease were analyzed by logistic regression analysis. Results: The overall rate of sensitization to SEA/SEB was 25.7%, whereas the rate of the AD only group (45.5%) was significantly higher than that of the AR/BA only group (24.5%, χ2 = 8.1). After sensitization to SEA/SEB, the geometric mean total IgE levels were significantly elevated in patients with AR+AHR and BA, but not in those with AR only. BA patients had higher geometric mean values of SEA- and SEB-specific IgE than AR only and AR+AHR patients. Logistic regression revealed that AR/BA only was more associated with sensitization to SEA/SEB (odds ratio 6.57) than AD only and AR/BA+AD (odds ratio 2.44 and 1.72). Conclusions: Atopic status after sensitization to SEA/SEB was more closely associated with BA than with other airway allergy, implying that SEA/SEB may play a role in exacerbating airway allergy and increasing the risk of allergic airway disease. Our study suggests that staphylococcal enterotoxins play a prominent role in the pathogenesis of allergic airway disease as well as AD.
Meta-Analysis of the Efficacy of Ebastine 20 mg Compared to Loratadine 10 mg and Placebo in the Symptomatic Treatment of Seasonal Allergic Rhinitis
Authors: Ratner Paul , Falqués Meritxell , Chuecos Ferran , Esbrí Ramon , Gispert Juan , Peris Francesc , Luria Xavier , Rosales María José
Published: October 2005

Background: Few randomized studies have compared the efficacy of ebastine and loratadine in the symptomatic treatment of seasonal allergic rhinitis (SAR). Methods: A meta-analysis was performed on data from four randomized, double-blind, placebo-controlled, parallel-group clinical trials comparing the efficacy of ebastine 20 mg once daily versus loratadine 10 mg once daily in the symptomatic treatment of SAR symptoms. Primary efficacy variable was the mean change in the overall mean daily reflective total symptom score (TSS), i.e. the sum of five rhinitis symptom scores: nasal discharge, nasal congestion, nasal itching, sneezing and total eye symptoms (itchy/watery eyes) over the first 2 weeks of treatment compared to baseline. Results: There were 2,089 patients in the population analyzed: 749, 739 and 601 patients in the ebastine 20 mg, loratadine 10 mg and placebo groups, respectively. Compared to baseline, overall mean daily reflective TSS over the first 2 weeks of treatment was –3.61 (35.4% reduction from baseline) in the ebastine group, –3.05 (29.0% reduction) in the loratadine group and –2.30 (22.7% reduction) in the placebo group. Statistically significant differences in the mean change from baseline were found when comparing ebastine and loratadine (p < 0.001), ebastine and placebo (p < 0.0001), and loratadine and placebo (p < 0.0001). The global effect (i.e. the difference in overall mean daily reflective TSS over the first 2 weeks of treatment) of ebastine compared with loratadine over the first 2 weeks of treatment was –0.56 (95% confidence interval, CI, –0.86 to –0.26), and it was sustained during the whole (4-week) period studied. The global effects of ebastine and loratadine compared with placebo were –1.30 (95% CI, –1.61 to –0.99) and –0.74 (95% CI, –1.05 to –0.43), respectively. Secondary variables (reflective and snapshot individual symptom scores) showed the same trend. Conclusions: This meta-analysis confirms that ebastine 20 mg has a good efficacy profile, inducing a greater decrease from baseline in mean rhinitis symptom scores than loratadine 10 mg or placebo.
A New Method of Oral Drug Provocation Testing for Determining Safe Alternatives for Patients with Non-Steroidal Anti-Inflammatory Drug Intolerance: The Triple Test
Authors: Kalyoncu A.F. , Karakaya G. , Bozkurt B. , Artvinli M.
Published: October 2005

Background: Although some of the non-steroidal anti-inflammatory drugs (NSAIDs) are reported to be safe for NSAID-intolerant patients, they should not be suggested before confirming the safety by single-blind oral drug provocation tests. Various test protocols are used in different allergy centers. The aim of this survey was to find out if testing three drugs a day could be a safe, time-saving and cost-effective method. Methods: We have enrolled 84 patients into this survey between September 1, 2002, and July 31, 2004. Results: Their mean age was 37.3 ± 11.0 years; 63 (75%) patients were female. By reliable history, the NSAID most commonly causing intolerance was aspirin (46.4%), and the most common reaction to analgesic intolerance was angioedema (60.7%). Eighty-seven tests were performed with meloxicam, rofecoxib, celecoxib, benzydamine, azapropazone, codeine and paracetamol in various triple combinations. Seventeen of the triple tests were positive, and one of them was suspiciously positive. After repeating these 18 tests with the same analgesics in the same order on 54 separate days, we have determined the responsible analgesics for 14 of the triple tests. There were no reactions when four of the triple tests were repeated on separate days (two of the triple tests demonstrated urticaria and the other two angioedema). Five patients had nausea and vomiting, and 2 had abdominal pain and other dyspeptic complaints during the tests. If we had performed the tests by the classical method, 264 days would have elapsed instead of 148 days (including the extra tests that we have performed after positive triple tests and gastrointestinal symptoms). Conclusion: The triple oral drug provocation testing seems to be a safe, time-/manpower-saving and cost-effective method for determining safe alternatives for NSAID-intolerant patients.