Mechanisms of matrix metalloproteinase-9 and matrix metalloproteinase-2 inhibition by N-acetylcysteine in the human term decidua and fetal membranes

OBJECTIVE: The purpose of this study was to evaluate the effect of N-acetylcysteine on the activity and secretion of the matrix metalloproteinases in the decidua, amnion, and chorion and the secretion of the tissue inhibitor of matrix metalloproteinase-1. STUDY DESIGN: Samples from eight nonlaboring women were taken at elective cesarean section and incubated in an in vitro organ culture in the absence or presence of N-acetylcysteine. Matrix metalloproteinase-2 and matrix metalloproteinase-9 activity was measured with the use of gel zymography. Western blot analysis was used to measure matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase-1 secretion. Data were analyzed with the paired Student t test. RESULTS: N-acetylcysteine had a direct inhibitory effect on matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, regardless of tissue origin, starting at 1.0 mmol/L. In cultured media, 20 mmol/L N-acetylcysteine inhibited matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in all three tissues. A differential response was demonstrated for matrix metalloproteinase-2 secretion, depending on the tissue that was studied. Its secretion was decreased in decidua at 10 mmol/L and 20 mmol/L; in amnion, the secretion was inhibited at 0.1 mmol/L and not affected at all in chorion. Matrix metalloproteinase-9 secretion was not affected in a statistically significant manner in any tissue. In the chorion, matrix metalloproteinase-9 showed a trend toward increased secretion. Tissue inhibitor of matrix metalloproteinase-1 secretion significantly decreased in the decidua at 20 mmol/L. CONCLUSION: N-acetylcysteine, at higher concentrations, has an inhibitory effect on matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, regardless of the tissue origin and the differential effect on secretion depending on the tissue and N-acetylcysteine concentration.     

Prenatal diagnosis of extrahepatic biliary duct atresia

A rare case of extrahepatic biliary atresia was diagnosed by a combination of prenatal ultrasound and measurements of fetal digestive enzymes in amniotic fluid. Ultrasound at 15 and 18 weeks' gestation failed to detect the gall bladder, and amniotic fluid digestive enzyme values were below the fifth percentile. The patient decided to terminate the pregnancy. Post-abortal pathological examination confirmed the diagnosis.     

Clinical and ultrasonographic weight estimation in large for gestational age fetus

OBJECTIVE: To examine prospectively the effect on pregnancy outcome of a management protocol, that adds ultrasonographic weight estimation in fetuses suspected clinically as large. STUDY DESIGN: Prospective follow up study of all singleton deliveries during a 1 year period. All patients underwent routine clinical estimation of fetal weight. When clinical estimation of fetal weight was > or = 3700 g, patients were referred for ultrasonographic estimation of fetal weight. When the latter was > or = 4000 g the patient was informed about the risks of birth trauma. Cesarean section was recommended only when > or = 4500 g. Ultrasonography was repeated every 4 days when possible. Predictive values of clinical and ultrasonographic estimations of fetal weight for diagnosing macrosomia, defined for the purpose of this study as 4000 g or more, and their effect on the rate of cesarean sections. RESULTS: Five hundred fifty-five (14.4%) out of 3844 singletons were estimated as 3700 g or more. Only 315 fetuses had ultrasonographic estimation of weight within 3 days of delivery. The sensitivity of clinical and ultrasonographic prediction of macrosomia was 68 and 58%, respectively. Cesarean section rate in newborns weighing 4000 g or more was 22% when macrosomia was clinically suspected compared to 11% when it was not (P<0.05). In fetuses estimated ultrasonographically as 4000 g or larger the cesarean section rate was doubled (50.7% versus 24.9%, P<0.05) compared to those estimated as smaller than 4000 g, although actual weight of 4500 g or more was recorded in 10.6 and 8.5% of these groups, respectively. There were no cases of shoulder dystocia in macrosomic babies when macrosomia was not detected by ultrasound compared to two cases of shoulder dystocia (2.7%) when macrosomia was detected by ultrasound. CONCLUSION: Antenatal suspicion of macrosomia increased the cesarean section rate while the associated improvement in pregnancy outcome remains questionable. The contribution of ultrasound, added to routine clinical estimation of fetal weight, was clinically insignificant apart from a further increase in cesarean section rate.     

Implicit location encoding via stored representations of familiar objects: neuropsychological evidence

We report data on the visual localisation ability of a patient with Balint's syndrome, GK. We show that, with relatively long exposures of displays, GK is better able to judge the spatial relations between separate objects (a "between-object judgement") than the spatial relations between a part and a whole object (a "within-object judgement") (Experiments 1-3). This dissociation occurred even when the same stimulus was used for both judgements, and the task instructions biased GK to parse the stimulus as either a single or as two separate objects (Experiments 2 and 6). However, when he could use a stored representation to make a within-object judgement, then performance was better than on a comparable spatial judgement of the relations between two separate objects (Experiments 4-7). The data demonstrate that stored representations of objects can support the spatial coding of parts to perceptual wholes. In the absence of stored representations, part-whole relations must be explicitly coded by attention, a process that is impaired in this patient.     

Retinopathy of prematurity: molecular pathology and therapeutic strategies

Retinopathy of prematurity (ROP) is an ischemia-induced proliferative retinopathy, which affects premature infants with low birth weight. It is a leading cause of visual impairment and blindness in children, and shares pathophysiological characteristics with other common ocular diseases such as diabetic retinopathy, central vein occlusion, and age-related macular degeneration. Pathologically similar inherited diseases such as Norrie disease suggest a possible genetic component in the susceptibility to ROP. The process of retinal neovascularization in ROP and in animal models of oxygen-induced retinopathy is complex, and involves angiogenic factors, such as vascular endothelial growth factor, and basement membrane components. Potential medical therapies for ROP, including modulators of angiogenic factors, inhibitors of basement membrane changes, endogenous inhibitors such as pigment epithelium derived factor, and anti-inflammatory drugs, have shown efficacy against neovascularization in several animal models. Some of these therapies are in clinical trials now for diabetic retinopathy and age-related macular degeneration, and in the future may prove efficacious for the treatment of ROP.     

Comparison of blood pressure measurements on the bare arm, below a rolled-up sleeve, or over a sleeve

BACKGROUND: This study examined the effect of measuring blood pressure below subjects' rolled-up sleeves, over the sleeve, or on the bare arm. This is an important day-to-day issue for the busy GP. METHODS: The sample consisted of 201 subjects in family practice clinics and residents of a senior citizens' home. A digital device was used in all cases. Each participant underwent three blood pressure measurements in each of the following conditions in random order: cuff on bare arm; cuff over the sleeve; and cuff below the rolled-up sleeve. Differences between measurements were plotted against the mean blood pressure. Confounding factors controlled for were age, sex, clothing pressure and skin-fold thickness. RESULTS: Differences in mean blood pressure readings between the clothed and bare arm were 0.5 mmHg (SD 7.5) for systolic pressure and 1 mmHg (SD 5) for diastolic pressure; neither difference was significant. However, in hypertensive subjects (>140 mmHg systolic), although the mean difference remained small (systolic pressure, 2 mmHg, SD 10), the range of difference for individual subjects was -32 mmHg to +22 mmHg. CONCLUSION: The degree of clothing under the sphygmomanometer cuff does not have a clinically important effect on the blood pressure measurement. In patients known or found to be hypertensive, measurement on the bare arm is recommended.     

The reinstatement model of drug relapse: history,methodology and major findings

Rational and objectives. The reinstatement model is currently used in many laboratories to investigate mechanisms underlying relapse to drug seeking. Here, we review briefly the history of the model and describe the different procedures that have been used to study the phenomenon of reinstatement of drug seeking. The results from studies using pharmacological and neuroanatomical techniques to determine the neuronal events that mediate reinstatement of heroin, cocaine and alcohol seeking by acute priming injections of drugs, drug-associated cues and environmental stressors are summarized. In addition, several issues are discussed, including (1) the concordance between the neuronal mechanisms involved in drug-induced reinstatement and those involved in drug reward and discrimination, (2) the role of drug withdrawal states and periods in reinstatement of drug seeking, (3) the role of neuronal adaptations induced by exposure to drugs in relapse, and (4) the degree to which the rat reinstatement model provides a suitable preclinical model of relapse to drug taking. Conclusions. The data derived from studies using the reinstatement model suggest that the neuronal events that mediate drug-, cue- and stress-induced reinstatement of drug seeking are not identical, that the mechanisms underlying drug-induced reinstatement are to some degree different from those mediating drug discrimination or reward, and that the duration of the withdrawal period following cocaine and heroin self-administration has a profound effect on reinstatement induced by drug cues and stress. Finally, there appears to be a good correspondence between the events that induce reinstatement in laboratory animals and those that provoke relapse in humans.     

Speed of performance of children with developmental right hemisphere syndrome and with attention-deficit hyperactivity disorder

Slowness is a common complaint in children with attention-deficit hyperactivity disorder (ADHD) and with developmental right hemisphere syndrome. However, it was our clinical impression that slowness in developmental right hemisphere syndrome was more prominent than in ADHD. Our objective was to assess slowness as operationalized by speed of performance in children with developmental right hemisphere syndrome, children with ADHD, and controls. The research sample comprised 19 children in each group, matched for age, gender, socioeconomic status, IQ, and handedness. The subjects were administered a reaction time battery assessing speed of performance. Overall, the average performance differed among the three study groups (F(2,53) = 2.40, P < .01). Children with developmental right hemisphere syndrome were slower than their peers with ADHD (t(35) = 1.99, P < .05) and slower than controls (t(35) = 4.55, P < .001). Children with ADHD performed more slowly than controls, although for the majority of tasks, this was nonsignificant. We conclude that slowness is an integral and consistent component of developmental right hemisphere syndrome and cannot be attributed only to the ADHD symptomatology.