Correlation between otitis media with effusion and cranial deformation in children.

OBJECTIVE: Otitis media with effusion (OME), defined as the presence of fluid in the ear without signs of an acute infection, usually occurs after acute otitis media and could result in reduced sound transmission with hearing loss. Several risk factors have been suggested to be associated with OME, as well as the relationships between morphology anomalies of cranial bones and ear infections. The aim of this study is to investigate the correlation between OME and cranial deformation in a pediatric population. PATIENTS AND METHODS: Eighteen children (13 males and 5 females) with a diagnosis of unilateral OME based on otolaryngologic examination, conductive hearing loss and an asymmetric tympanogram type were enrolled in the study. Patients underwent osteopathic and physical examinations to evaluate the presence of cranial deformations. RESULTS: Our study showed a high percentage of skull asymmetry (94%) in the study sample; children were mainly dolichocephalic and with atypical swallowing (72%). Particularly, we observed an occipital flattening, mainly ipsilateral to the ear affected by OME. CONCLUSIONS: The results of the present study indicated that a high percentage of children with OME present a skull asymmetry with concomitant dolichocephaly, known to be associated with high arched palate which is also related to a higher incidence of OME.

The anxiolitic effects of BTG1640 and BTG1675A on ultrasonic isolation calls and locomotor activity of rat pups.

OBJECTIVE: The aim of the present study was to evaluate the anxiolytic properties of the new isoxazoline compounds BTG1640 and BTG1675A in comparison with diazepam. MATERIALS AND METHODS: We evaluated the ultrasonic distress emission in both sexes of neonatal rat pups (which seems to be a sensitive indicator of the rat emotional reactivity and represents a valuable tool to screen compounds with expected anxiolytic properties) and the locomotor activity in 30-day old rat pups. RESULTS: We found a significant reduction in the number of emitted ultrasonic calls only after i.p. administration of diazepam 1 mg/kg, while no significant reduction have been detected after i.p. administration of BTG 1640 and BTG 1675A. Furthermore, we found a significant reduction of locomotor activity in the first 10' of the test, only in the group treated with diazepam 0.1 mg. CONCLUSIONS: The tests validating the supposed anxiolytic properties of the new isoxazoline compounds BTG1640 and BTG1675A, in comparison with diazepam, gave negative results.

Neurobehavioral studies, in transgenic F3/CONTACTIN (C57BL/6J × CBA) mice, on cognitive and anxiety aspects during late-adolescential period.

OBJECTIVE: Besides than in the control of developmental events, axonal adhesive glycoproteins may be also involved in functions requiring fine organization and connectivity of the nervous tissue. We previously demonstrated morphological alterations and functional cerebellar deficits in transgenic mice (TAG/F3 mice) ectopically expressing the F3/Contactin axonal glycoprotein under the control of a selected regulatory region from the Transient Axonal Glycoprotein (TAG-1) gene. In the present study, the hippocampal function was explored by evaluating the ability of TAG/F3 mice to encode spatial and non-spatial relationships between discrete stimuli and to analyze an anxiety-related behavior. MATERIALS AND METHODS: To the first end, mice were placed in an "open-Field" containing five objects and, after three sessions of habituation (S2-S4), their reactivity to objects displacement (S5-S4) and object substitution (S7-S6) was examined.To the second end, mice were placed in the "elevated zero maze", a standard test to explore the anxiety-related behavior, in order to study, in transgenic mice, the effects of F3 misexpression on emotional reactivity by measuring the avoidance of the unsheltered open sectors. RESULTS: Statistical evaluations of reactivity to object novelty, TAG-F3 mice showed a lower DO exploration with respect to wild-type mice and, regarding DOs, TAG/F3 mice interacted less than wild-type mice, showing an impaired spatial change response. Furthermore, the number of HDIPS in transgenic TAG/F3 mice resulted significantly lower with respect to the controls (wild type). CONCLUSIONS: These results indicate that the coordinated expression of axonal adhesive glycoproteins may be relevant for the functional maturation of the hippocampus.

Meniscal tears left in situ during anatomic single bundle anterior cruciate ligament reconstruction.

OBJECTIVES: Anterior cruciate ligament (ACL) injuries are a common finding in sports medicine. Our scope is to investigate whether stable, incomplete medial meniscus tears could be left untreated during single bundle anatomic anterior cruciate ligament reconstruction. PATIENTS AND METHODS: A prospective observational study on 597 knees from a single surgeon cohort, using the same reconstruction technique, found 23 medial and 48 lateral meniscus tears which could be left untreated. RESULTS: None of the cases required reintervention during the first postoperative year. In fact, 21.7% of the medial meniscus group and 14.6% of the lateral group had potential residual symptoms that were not confirmed and gradually disappeared within one year. A comparison of Cincinnati Knee, IKDC scores and limb symmetry index values (calculated using the triple hop for distance into the two groups) found no differences for the last two variables (both p = 0.065) and was marginal for the first score (p < 0.05). The between groups comparisons, performed in the KT-1000, also yielded no difference (p = 0.11). CONCLUSIONS: We than concluded that incomplete meniscal tears, left in situ at the time of anterior cruciate ligament reconstruction, could have favorable outcomes as long as decisions are carefully weighed with regard to the length of the lesion. Also, at least in this perspective, anatomic single bundle has proved a sufficient stabilizer for anterior translation of the tibia.

Patient-oriented rehabilitation in the management of chronic mechanical neck pain: a randomized controlled trial.

BACKGROUND: Management of chronic mechanical neck pain (CMNP) still represents a challenge. A patient-oriented (Pa-O) therapeutic approach could be considered as the one in which therapies are scheduled at the start of each therapeutic session according to the patient's current physical status, and differs from a prescription-oriented (Pr-O) therapeutic approach, in which therapies are prescribed at the first medical referral and are not adjusted at any time during the treatment period. AIM: To determine if a Pa-O approach may be more beneficial for CMNP patients when compared to a Pr-O one. DESIGN: Randomized controlled trial. POPULATION: 220 CMNP outpatients randomized to either Pa-O group (N.=114) or Pr-O group (N.=106). METHODS: Each group received 10 therapeutic sessions over 3 weeks. Primary outcome measures were pain assessment, evaluated by Visual-Analog-Scale (VAS), and disability level, evaluated by the Neck Pain and Disability Scale (NPDS-I). Secondary outcome measures included patients' response to treatment and treatment failures. Measurements were carried out at baseline (T0) and 1 month after treatment ended (T1). Data were analysed according to the intention-to-treat principle. RESULTS: Patients in both groups displayed at T1 a significant reduction in VAS and NPDS-I scores. The relative changes at T1 were greater in Pa-O group when compared with Pr-O group both for VAS (61.5% versus 48.8%; P<0.005) and for NPDS-I scores (48.4% versus 36.8%; P<0.05). CONCLUSION: A Pa-O approach may be more beneficial in terms of pain and disability improvement in the short-term follow-up in suffers from CMNP. However, the occurrence of a performance-bias due to the increased level of attention from physicians to patients in Pa-O group, cannot be ruled-out. CLINICAL REHABILITATION IMPACT: A Pa-O approach should be considered for CMNP also in an outpatient facility.

Prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 and carbon monoxide reduces extracellular glutamate levels in primary rat cerebral cortex cell cultures.

The effects of prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 (0.5 mg/kg s.c.), alone or in combination with carbon monoxide, on extracellular glutamate levels in primary rat cerebral cortical neuronal cultures, were investigated. Dam weight gain, pregnancy length and litter size at birth were not affected by prenatal treatment with WIN 55,212-2 and carbon monoxide alone or in combination. Basal and K(+)-evoked extracellular glutamate levels were reduced in cortical cultures from pups born to mothers exposed to WIN 55,212-2 and carbon monoxide alone or in combination compared to cultures from rats born to vehicle-treated mothers. In cultures obtained from rats exposed to vehicle or carbon monoxide alone during gestation, WIN 55,212-2 (0.01-100 nM) increased extracellular glutamate levels, displaying a bell-shaped concentration-response curve. In cultures from rats born to mothers exposed to WIN 55,212-2 alone or in combination with carbon monoxide the WIN 55,212-2 ( 1 nM)-induced increase in extracellular glutamate levels was lower than that observed in cultures from rats born to vehicle-treated mothers and similar at those observed at 10 and 100 nM concentrations. The selective CB1 receptor antagonist SR141716A (10 nM) counteracted the WIN 55,212-2-induced increase in extracellular glutamate levels in cultures exposed to vehicle or carbon monoxide during gestation, but failed to antagonise it in cultures from rats born to mothers exposed to WIN 55,212-2 alone or in combination with carbon monoxide. These findings provide evidence that prenatal exposure to the cannabinoid receptor agonist WIN 55,212-2 and carbon monoxide, alone or in combination, is associated with an impairment in cortical glutamatergic transmission. It could be speculated that such detrimental effects might be involved in the reported deficit in learning and memory associated with prenatal marijuana exposure.

Transgenic mice expressing F3/contactin from the transient axonal glycoprotein promoter undergo developmentally regulated deficits of the cerebellar function.

We have shown that transgenic transient axonal glycoprotein (TAG)/F3 mice, in which the mouse axonal glycoprotein F3/contactin was misexpressed from a regulatory region of the gene encoding the transient axonal glycoprotein TAG-1, exhibit a transient disruption of cerebellar granule and Purkinje cell development [Development 130 (2003) 29]. In the present study we explore the neurobehavioural consequences of this mutation. We report on assays of reproductive parameters (gestation length, litter size and offspring viability) and on somatic and neurobehavioural end-points (sensorimotor development, homing performance, motor activity, motor coordination and motor learning). Compared with wild-type littermates, TAG/F3 mice display delayed sensorimotor development, reduced exploratory activity and impaired motor activity, motor coordination and motor learning. The latter parameters, in particular, were affected also in adult mice, despite the apparent recovery of cerebellar morphology, suggesting that subtle changes of neuronal circuitry persist in these animals after development is complete. These behavioural deficits indicate that the finely coordinated expression of immunoglobulin-like cell adhesion molecules such as TAG-1 and F3/contactin is of key relevance to the functional, as well as morphological maturation of the cerebellum.

Prenatal low-level exposure to CO alters postnatal development of hippocampal nitric oxide synthase and haem-oxygenase activities in rats.

The effects of prenatal CO exposure (150 ppm from days 0 to 20 of pregnancy) on the postnatal development of hippocampal neuronal NO synthase (nNOS) and haem-oxygenase (HO-2) isoform activities in 15-, 30- and 90-d-old rats were investigated. Unlike HO-2, hippocampal nNOS activity increased from postnatal days 15-90 in controls. Prenatal CO produced a long-lasting decrease in either nNOS or HO-2. The results suggest that the altered developmental profile of hippocampal nNOS and HO-2 activities could be involved in cognitive deficits and long-term potentiation dysfunction exhibited by rats prenatally exposed to CO levels resulting in carboxyhaemoglobin (HbCO) levels equivalent to those observed in human cigarette smokers.

Effects of ENA713 and CHF2819, two anti-Alzheimer's disease drugs, on rat amino acid levels.

The effects of oral ENA713 and CHF2819 (0.5, 1.5 and 4.5 mg/kg), two novel acetylcholinesterase inhibitors, on extracellular concentrations of amino acids in rat hippocampus, were evaluated using in vivo microdialysis. ENA713, at 4.5 mg/kg, but not CHF2819, significantly decreased glutamate, taurine, arginine and citrulline levels, without affecting aspartate concentrations. These results suggest that the modulation of amino acidergic transmission could represent an additional mechanism of action in Alzheimer's disease for some acetylcholinesterase inhibitors.

Neurofunctional effects of developmental alcohol exposure in alcohol-preferring and alcohol-nonpreferring rats.

The neurofunctional effects of developmental alcohol exposure (3% v/v solution from day 15 of gestation to day 7 after parturition) have been investigated in Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rat lines, selectively bred for opposite alcohol preference and consumption. Alcohol exposure significantly decreased the rate of ultrasonic emission in sP male pups; whereas, it did not affect this indicator of emotional reactivity in sNP animals. Perinatal alcohol intake did not influence either learning of an active avoidance task or hippocampal long-term potentiation in both offspring lines. Significant differences in time spent exploring novel objects were observed between control sP and sNP rats subjected to the novel exploration object test. Alcohol exposed sP rats, but not alcohol exposed sNP rats, apparently lost the capacity to discriminate between the novel and the familiar object, even though this difference is difficult to interpret because of the large differences in the respective responses to the novel objects. Neurochemical experiments have shown that basal levels of dopamine (DA) and homovanillic acid (HVA) were significantly higher in the nucleus accumbens (NAC) of sP rats with respect to sNP animals. Perinatal alcohol did not affect basal DA and HVA concentrations or amphetamine-induced DA increase and HVA decrease in the NAC of either sP or sNP offspring. These results suggest that subtle behavioral alterations induced by developmental exposure to low doses of alcohol, which do not cause malformations and/or overt neurotoxicity, may be associated with genetic factors, although not necessarily those responsible for differences in alcohol preference.

Persistent eradication of Helicobacter pylori after systemic politherapy associated with periodontal pockets treatment with metronidazole and calcium sulphate.

The sensitivity of H. Pylori to antibiotic treatment is well known. Politherapy (omeprazole or pantoprazole or ranitidine, amoxicillin and/or azithromycin and/or clarithromycin, metronidazole and bismuth citrate) notably changed the percentage of H. pylori eradication but rarely resolutive. Periodontal pockets treatment with topic metronidazole, calcium sulphate and potassium sulphate resulted active against bacteria included in periodontal pockets leading to a long-term H. pylori eradication (two years follow-up).

Prenatal exposure to low levels of carbon monoxide alters sciatic nerve myelination in rat offspring.

Prenatal exposure to low concentrations of carbon monoxide (CO, 75 and 150 ppm from day 0 to day 20 of gestation), resulting in maternal blood HbCO concentrations equivalent to those maintained by human cigarette smokers, leads to subtle myelin alterations in the sciatic nerve of male rat offspring. The rapid growth spurt in pup body weight was related to the period of maximal increase in myelin sheath thickness in both control and CO-exposed animals. A significant reduction in myelin sheath thickness of sciatic nerve fibers, paralleled by changes in the frequency distribution, occurred in both 40- and 90-day-old rats exposed in utero to CO (75 and 150 ppm). Myelin deficit observed in 75 and 150 ppm CO-exposed animals showed up only after the major spurt in myelination but not early during development. The subtle myelin alterations observed in CO-exposed offspring were not accompanied by changes in developmental pattern of axon diameters and did not result in a gross impairment of motor activity. These results suggest that the myelination process is selectively targeted by a prenatal exposure model simulating the CO exposure observed in human cigarette smokers.

Prenatal exposure model simulating CO inhalation in human cigarette smokers: sphingomyelin alterations in the rat sciatic nerve.

Prenatal exposure to low concentrations of carbon monoxide (CO, 150 ppm) causes long-term alterations in sphingomyelin (SM) homeostasis in peripheral nervous system, but not brain of male rat offspring. In particular, unlike sphinganine (intermediate of complex sphingolipid biosynthesis de novo), the concentrations of sphingosine (intermediate of complex sphingolipid turnover) were increased by 2.35-fold in the sciatic nerve of CO-exposed offspring with respect to controls (P<0.05, overall one-way ANOVA). These subtle alterations were not accompanied by changes in motor activity (F=0.25, df=1/10, n.s., overall one-way-ANOVA). The results suggest that the SM homeostasis in the sciatic nerve is particularly susceptible to prenatal CO exposure resulting in maternal carboxyhaemoglobin (HbCO) levels equivalent to those found in human cigarette smokers.

Prenatal exposure to a low concentration of carbon monoxide disrupts hippocampal long-term potentiation in rat offspring.

The aim of the present study was to investigate whether functional changes at CA3-CA1 synapses in the hippocampus could underlie learning and memory deficits produced in rat offspring by a prenatal exposure model simulating the carbon monoxide (CO) exposure observed in human cigarette smokers. Electrophysiological endpoints, including long-term potentiation, were examined in 15- to 30-day-old male rats whose mothers were exposed, from day 0 to day 20 of gestation, to 150 ppm of CO resulting in blood levels of carboxyhemoglobin comparable to those found in human cigarette smokers. Evoked field excitatory postsynaptic potentials were measured in the stratum radiatum in hippocampal slices. Results show that before tetanus, input/output functions, presynaptic volley, and paired-pulse facilitation were not affected in CO-exposed offspring, indicating that basal synaptic excitability and terminal Ca(2+) influx were not influenced by prenatal exposure to this gas. Conversely, evoked field excitatory postsynaptic potentials potentiation in response to tetanization was reduced by about 23% and decayed rapidly to baseline values in slices from CO-exposed animals. No changes between and within groups were observed in paired-pulse facilitation after tetanus. The selective impairment of long-term potentiation expression exhibited by CO-exposed rats was paralleled by a significant decrease in heme-oxygenase 2 and neuronal nitric-oxide synthase in the hippocampus. No changes in either enzymatic activity were found in frontal cortex and cerebellum. These electrophysiological and biochemical alterations might account for cognitive deficits previously observed in rats exposed prenatally to CO. Our findings could have clinical implications for the offspring of mothers who smoke during pregnancy.

In vivo neurochemical effects of the acetylcholinesterase inhibitor ENA713 in rat hippocampus.

Oral ENA713 (0.5, 1.5 and 4.5 mg/kg), an acetylcholinesterase inhibitor (AChEI), dose-dependently enhanced extracellular acetylcholine concentrations in the hippocampus of freely moving rats. This effect was paralleled by changes in both noradrenergic and dopaminergic transmission. In particular, ENA713 significantly decreased noradrenaline concentrations, whereas it significantly increased homovanillic acid levels, without affecting dopamine concentrations. Neither serotonin nor gamma-aminobutyric acid levels were modified by ENA713. These findings extend the neurochemical profile of ENA713 and suggest that it could be useful for the treatment of Alzheimer-type dementia which is associated with multiple neurotransmitter abnormalities in the brain.

Prenatal exposure to low concentrations of carbon monoxide alters habituation and non-spatial working memory in rat offspring.

Inhalation of low concentrations (75 and 150 ppm) of carbon monoxide (CO) by pregnant rats from days 0 to 20 of gestation leads to alterations in habituation and working memory in young adult male offspring subjected to the novel exploration object test. In particular, lack of habituation upon the second presentation of the objects and failure in the ability to discriminate between the novel and the familiar object were found in CO (75 and 150 ppm)-exposed offspring. These alterations were not accompanied by changes in spontaneous motor activity (open field test). The subtle behavioral deficits observed in the present study have been produced by prenatal exposure to CO levels resulting in maternal blood carboxyhaemoglobin (HbCO) concentrations equivalent to those observed in human cigarette smokers.

Effects of early postnatal exposure to low concentrations of carbon monoxide on cognitive functions in rats.

Male Wistar rats were exposed to 75 and 150 ppm of carbon monoxide (CO) from day 1 after birth until postnatal day 10 and their cognitive functions were evaluated at 3 and 18 months of age. The results show that early postnatal exposure to CO does not affect the acquisition and reacquisition of an active avoidance task in both adult and aged rats. Conversely, our previous findings indicate that prenatal exposure to CO (75 and 150 ppm), resulting in maternal blood carboxyhaemoglobin concentrations equivalent to those found in human cigarette smokers, induces long-lasting learning and memory deficits. These findings suggest that neurofunctional sequelae of prenatal CO exposure are notably different from those occurring in response to early postnatal exposure and that the vulnerability of the developing brain to prolonged, relatively mild, decrease in oxygen availability induced by CO critically depends on the particular period of developmental exposure.

Effects of site-directed mutagenesis of protolytic residues in subunit I of Bacillus subtilis aa3-600 quinol oxidase. Role of lysine 304 in proton translocation.

Various protolytic residues in subunit I of aa3-600 quinol oxidase of the aerobic Gram-positive Bacillus subtilis were mutagenized to nonpolar residues. Two of the mutations, Y284F and K304L, impaired the bioenergetic function of the microorganism. The Y284F mutation suppressed the electron-transfer activity of quinol oxidase and altered its interaction with CO and H2O2, thus showing destruction of the binuclear domain as observed for the bo3 quinol oxidase of Escherichia coli. The K304L mutation did not alter significantly the redox activity of the oxidase and its interaction with CO and H2O2 but suppressed the proton pumping activity of the enzyme. These results show that the K304 residue, which is invariantly conserved (as K or R) in practically all the sequences of the heme-copper oxidases so far available (around 100), is essential for the proton pumping activity of the oxidase.

Effects of prenatal exposure to low concentrations of carbon monoxide on sexual behaviour and mesolimbic dopaminergic function in rat offspring.

1. Inhalation of low concentrations of carbon monoxide (CO) by pregnant rats (75 and 150 p.p.m. from day 0 to day 20 of gestation) leads to changes in mesolimbic dopaminergic transmission associated with an impairment of sexual behaviour in male offspring. 2. Eighty day old males exposed in utero to CO (150 p.p.m.) exhibited a significant increase in mount/ intromission latency as well as a significant decrease in mount/intromission frequency. A significant decrease in ejaculation frequency was also found in CO (150 p.p.m.)-exposed animals. 3. The acute administration of amphetamine, at a dose (0.5 mg kg(-1) s.c.) stimulating copulatory activity in control rats, failed to reduce mount/intromission latency and did not increase mount frequency in 80-day offspring exposed to CO (150 p.p.m.) during gestation. 4. These behavioural alterations were paralleled by neurochemical changes (in vivo microdialysis) showing that prenatal CO exposure, at concentrations (150 p.p.m.) that did not affect basal extracellular levels of dopamine in the nucleus accumbens, blunted the amphetamine (0.5 mg kg(-1) s.c.)-induced increase in dopamine release in 80-day old male rats. 5. No significant changes in either behavioural or neurochemical parameters were observed in 10-month old rats exposed prenatally to CO. 6. Since the alterations in sexual behaviour and dopaminergic transmission have been produced by prenatal exposure to CO levels resulting in maternal blood carboxyhaemoglobin concentrations equivalent to those maintained by human cigarette smokers, the present data further point out the large risk that the smoking mother poses for her offspring.

Effects of chronic low-dose ethanol intake on sexual behavior in rats.

The effects of 8-week ethanol intake (3% v/v in drinking water) on the sexual activity of male rats were investigated during three experimental sessions with 15-day intersession intervals. Chronic ethanol consumption did not significantly influence any copulatory parameter during the three experimental sessions. The evaluation of ultrasonic emission during sexual behavior showed that rats treated with ethanol exhibited a significant increase of the postejaculatory vocalization length during the third test session. These results indicate that the chronic intake of low doses of ethanol, which does not induce either tolerance or dependence, only slightly affects the motivational state of male rats during sexual activity.