Effect of acetylated derivatives of some sympathomimetic amines on the isolated auricles and tracheal chain of the guinea-pig

The effects of acetylation of sympathomimetic amines, tyramine, amphetamine, ephedrine, phenylephrine, orciprenaline, and salbutamol, and their O- and N-acetyl derivatives and the effects of reserpine or physostigmine pretreatment on the isolated auricles and tracheal chain of guinea-pigs have been studied. All the parent drugs relaxed the tracheal chain and had a positive inotropic and chronotropic effect on the isolated auricles; only amphetamine, on the contrary, contracted the tracheal chain. O-acetylation of these sympathomimetic amines generally decreased less chronotropic than iontropic action on the isolated auricles. O-acetylation of tyramine however: actually increased the positive chronotropic activity of drug. As a rule, O-acetylation also decreased the beta-adrenergic effect of these compounds on the tracheal chain, but not so markedly as on the isolated auricles. N-acetylation generally abolished the adrenergic effects of these sympathomimetic amines on the isolated auricles and decreased those effects on the tracheal preparation. N,O-triacetylation of salbutamol abolished the stimulating effect of the parent drug on the auricles but increased the relaxant activity on the trachea.Physostigmine antagonized the effects of O-acetyltyramine and O-triacetylorciprenaline but not those of tyramine and orciprenaline on the trachea preparation. It is concluded that among the sympathomimetic amines acetylation may be utilized for the development of specific bronchodilators and O-acetylation for inducing drug latentiation.     

Aspartylglucosaminuria: Deficiency of aspartylglucosaminidase in cultured fibroblasts of patients and their heterozygous parents

Aspartylglucosaminuria (AGU) is a genetic lysosomal storage disorder which probably affects the metabolism of glycoproteins. Earlier studies have shown a deficiency of a lysosomal hydrolase, N-aspartyl-β-glucosaminidase in the serum and seminal fluid, as well as in the brain and liver tissues of the patients. The present studies demonstrated a very low activity of N-aspartyl-β-glucosaminidase in cultured skin fibroblasts from AGU patients. The fibroblasts of the parents of the patients had a moderately low enzyme activity when conipared with control cultures. Thus, demonstration of the enzyme defect in fibroblasts offers possibilities both for detection of heterozygotes and for prenatal diagnosis of AGU.     

Effect of sampling frames on response rates in the WHO MONICA risk factor surveys

Sample surveys are used to investigate occurrence and determinants of diseases in populations. Their reliability is influenced by quality of sampling frame and response rate. We investigated relationship between sampling frame type and response rates and assessed their impact on non-response bias, using data from the WHO MONICA Project, where 37 centres in 20 countries conducted sample surveys, employing the best locally available sampling frame. Sampling frames fell into three categories: Population registers (PR), electoral registers (ER), and health care registers (HR). Response rate (rrs) was factored into components reflecting quality of sampling frame (contact rate cr) and characterizing willingness of sample members to participate (enrolment rate er). The mean quality score for the sampling frames was 92 for PR, 87 for HR and 85 for ER; they contributed on average 23, 20, and 26 to the respective non-response rates. For all frame types and both sexes the lowest quality score occurred in the age group 35–44, suggesting a reduced ability to track migration of a highly mobile population group. The patterns in the age/sex distribution of er indicate at least for males in PR and females in HR a potential for non-response bias. Estimation of non-response bias through an abbreviated questionnaire failed because of low item response. We found that contact rate characterizes sampling frame quality. For all frame types it had a major influence on response rate. It is likely that low er and low cr cause different kind of bias, requiring different measures to minimize their effects.for the WHO MONICA Project** Sites and key personnel of the WHO MONICA Project are found at http://www.ktl.fi/publications/monica/rr_sframe/appendix.htm     

Dietary carbohydrate modification enhances insulin secretion in persons with the metabolic syndrome

BACKGROUND: The metabolic syndrome markedly increases the risk of type 2 diabetes and cardiovascular disease, but the influence of dietary modification on insulin and glucose metabolism independent of weight loss is still poorly understood. OBJECTIVE: Our aim was to test whether carbohydrate dietary modifications improve insulin sensitivity and secretion and glucose tolerance in overweight or obese persons with the metabolic syndrome, even in the absence of weight loss. DESIGN: We assessed the effect of carbohydrate modification on insulin and glucose metabolism in 72 overweight or obese men and women with the metabolic syndrome, as determined according to the National Cholesterol Education Program criteria. The subjects were randomly assigned to 12-wk diets in which either rye bread and pasta or oat and wheat bread and potato were the main carbohydrate sources (34% and 37% of energy intake, respectively). RESULTS: Body weight did not significantly change in either group during the trial. No significant difference was observed in the changes in fasting glucose and insulin concentrations or in glucose and insulin areas under the curve between the groups during a 2-h oral-glucose-tolerance test. The insulinogenic index (an index of early insulin secretion) increased more in the rye bread and pasta group than in the oat and wheat bread and potato group (33.2% compared with 5.5%; P = 0.026). In the combined groups, an enhanced insulinogenic index was associated with improved glucose tolerance, whereas weight gain worsened glucose tolerance. Moreover, even modest weight gains abolished the relative improvement in the insulinogenic index in the rye bread and pasta group compared with the oat and wheat bread and potato group (P for the interaction between weight change and group = 0.019). CONCLUSIONS: Rye bread and pasta-based carbohydrate modification enhances early insulin secretion in persons with the metabolic syndrome, which may lower the risk of deteriorating glucose tolerance and development of type 2 diabetes.     

Reversible hearing loss associated with high-voltage electric shock

Hearing loss associated with high-voltage electric shock is a rare entity and minimal information is available in the current literature about this condition. To our knowledge, this article represents the first case report in the literature of improvement in sensorineural hearing loss sustained due to a high-voltage electric shock. A case report of a patient who incurred various otologic problems, including hearing loss and tinnitus, is presented. An improvement in hearing loss and tinnitus was observed in the subsequent follow up after one month. Audiological findings and possible pathophysiology of hearing loss are discussed. We recommend that further studies be done to investigate the incidence, severity and pathophysiology of hearing loss in such cases.     

P1 latency as a biomarker for central auditory development in children with hearing impairment

We used the latency of the P1 cortical auditory-evoked potential (CAEP) as a biomarker for the development of central auditory pathways in three children who received intervention through hearing aids and/or cochlear implants. Our goal was to examine the clinical feasibility of using the latency of the P1 CAEP as an objective tool to evaluate whether acoustic amplification for hearing-impaired children has provided sufficient stimulation for normal development of central auditory pathways. If clinicians have such a marker, then they can more confidently make a decision about whether to provide a child with a cochlear implant following an appropriate hearing-aid trial. Using the same marker, clinicians will also be able to monitor the maturation of central auditory pathways once electrical stimulation is initiated.     

Processing of highly novel auditory events in children and adults: an event-related potential study

In this study, the neural mechanisms of novelty detection in children and adults were examined by means of novelty-elicited event-related potentials. The gross morphology of the event-related potentials elicited by complex, novel stimuli was similar in children and adults, suggesting that processing of novel acoustic information is essentially similar across the age groups. The more frontally distributed P3 components and the larger late frontal negativities in children than in adults suggest an age-related change in activity in the frontal part of the brain. This is consistent with the findings showing that the structural maturation of the frontal cortex does not appear to be completed until late adolescence.