Information for oral and maxillofacial patients: can it be improved?

The aim and objective of this study was to evaluate the quality and readability of leaflet and online Oral and Maxillofacial Surgery patient information leaflets (PILs). The quality, readability and grade level of each PIL was assessed using the DISCERN, Flesch Reading Ease and Flesh-Kincaid Grade Level instruments respectively. In total, 140 patient information leaflets were assessed. For both leaflet and online PILs, many items of the DISCERN instrument were deemed of low quality and poorly reported. The median overall quality score was 30.2. Variation in the quality and readability scores between leaflet and online PILs and those produced by various societies was evident. Overall, PILs were deemed to be of moderate quality. Online PILs were of lower quality, more difficult to read and aimed at a higher reading age level.

Chrononutrition applied to formula milks to consolidate infants' sleep/wake cycle.

UNLABELLED: Some 30% of pre-weaning infants present problems of sleep during the night, especially those who are bottle-fed. The solution is for them to be breast-fed for as long as possible, or, if this is not possible, for the formula milk to reproduce breast-milk's natural circadian variations in the concentrations of tryptophan and those nucleotides which have a beneficial effect in consolidating the circadian sleep-wake cycle. OBJECTIVE: To study in pre-weaning infants the effect on nocturnal sleep of the administration of formula milk dissociated into its day/night components. MATERIALS AND METHODS: A prospective study was carried out on 30 pre-weaning infants of 4-20 weeks in age who preferentially showed sleep problems. The day dissociated formula, administered from 06:00-18:00, had lower levels of tryptophan and carbohydrates, and higher levels of proteins together with cytosine-5P, guanosine-5P, and inosine-5P. The night dissociated formula, administered from 18:00-06:00, had lower levels of proteins and medium-chain triglycerides, higher levels of tryptophan and carbohydrates, together with adenosine-5P and uridine-5P. In a random, double-blind, design, three one-week diets were administered: Diet A (Control): normal initiation milk; Diet B: 06:00-18:00 normal initiation milk, 18:00-06:00 dissociated night formula; and Diet C: day/night formulas with the schedule given above. The sleep patterns were analyzed by means of actimeters (Actiwatch). Statistical analysis consisted of an ANOVA with a Scheffe F-test, taking a value of p<0.05 to be statistically significant. RESULTS: The children receiving the week of Diet C (with the day/night formulas in synchrony with the environment) showed increased hours of actual sleep (7.68 +/- 0.54 h vs. 6.77 +/- 0.12 h for the Diet A control) and improved sleep latency (0.44 +/- 0.04 h vs. 0.60 +/- 0.08 h for the Diet A control). The same children receiving the Diet B in another different week showed an improvement in sleep efficiency (76.43 +/- 3.4% vs. the Diet A control 69.86 +/- 0.94%) and sleep latency (0.45 +/- 0.04 h vs. the Diet A control 0.60 +/- 0.08h) The parents also reported, in response to follow-up questions, an improvement in the sleep of their infants during the Diet C week. CONCLUSION: Day/night infant formula milks designed according to the principles of chrononutrition help to consolidate the sleep/wake rhythm in bottle-fed infants.

The circadian rhythm of tryptophan in breast milk affects the rhythms of 6-sulfatoxymelatonin and sleep in newborn.

INTRODUCTION: The hormone melatonin regulates the sleep and this pineal hormone is synthesized in the organism from the amino acid tryptophan. It is known that breast-fed babies have better sleep patterns and a better entrained sleep/wake cycle than bottle-fed babies (adapted formula). OBJECTIVE: To compare the circadian rhythm of 6-sulfatoxymelatonin (aMT6s)--the metabolite of melatonin excreted in the urine--in urine of bottle-fed and breast-fed children, and relate it to the circadian rhythm of tryptophan in breast milk, also evaluating the possible effects on the baby's night-time rest. METHODS: 16 infants of 12 weeks of age were studied, divided into two groups depending on their exclusively natural or artificial feeding. The circadian rhythm of 6-sulfatoxymelatonin in urine was measured for the two groups of infants and for the breast-feeding mothers. In the breast milk, the circadian rhythm of the amino acid tryptophan was measured. The rest of the infants was tested by wrist actimeters for a week and the sleep parameters of the infants were measured and evaluated. RESULTS: The tryptophan in the breast milk presented a circadian rhythm with acrophase at around 03:00. This affected the 6-sulfatoxymelatonin circadian rhythm with acrophase at 06:00 in the breast-fed infants, and also promoted nocturnal sleep. Assumed sleep, actual sleep, and sleep efficiency were significantly increased in the breast fed infants with respect the formula fed infants. CONCLUSION: A temporal relationship was observed between the circadian rhythm of 6-sulfatoxymelatonin of the exclusively breast-fed babies and that of tryptophan in the mother's milk. Acting this amino acid as a zeitgeber entrainment of the biological rhythms in the breast-fed infant.

Noradrenaline stimulates 5-hydroxytryptamine release from mouse ileal tissues via alpha(2)-adrenoceptors.

The effect of noradrenaline on 5-hydroxytryptamine (5-HT) release from isolated mouse ileal tissues was investigated. Noradrenaline, but not isoprenaline, at 1 microM stimulated 5-HT release, an effect which was inhibited by yohimbine, an alpha(2)-adrenoceptor antagonist, but not by bunazosin, an alpha(1)-adrenoceptor antagonist. alpha(2)-Adrenoceptor agonists, UK 14,304 (5-bromo-6-(2-imidazolin-2-yl-amino)-quinoxaline) and clonidine at a higher concentration (10 microM) also stimulated 5-HT release, while alpha(1)-adrenoceptor agonists, methoxamine and phenylephrine, had no effect. The effect of noradrenaline was completely abolished in ileal tissues isolated from mouse treated with pertussis toxin (100 microg/kg, i.v.) for 2 days. These results suggest that noradrenaline causes 5-HT release from enterochromaffin cells in mouse ileal tissues via alpha(2)-adrenoceptor subtypes coupled to a pertussis toxin-sensitive G protein.

L-arginine stimulates insulin secretion from the pancreas of normal and diabetic rats.

Several reports have shown that nitric oxide (NO) stimulates glucose-induced insulin secretion in the pancreas of normal rat but the effect of L-arginine (a NO donor) on insulin secretion from the pancreas of diabetic pancreas is unknown. Fragments of pancreatic tissue from normal and diabetic rats were incubated for 45 min in Krebs solution containing 100mM L-arginine. The supernatant was subsequently analyzed for the insulin content using radioimmunoassay technique. L-arginine evoked large increases in insulin secretion from the pancreas of diabetic rat. The insulin secreted from the pancreas of diabetic rat was numerically but not significantly lower compared to that of normal rat pancreas. In conclusion, L-arginine, a nitric oxide donor stimulates insulin secretion from the pancreas of diabetic rats.

Conformational toxicity and sporadic conformational diseases.

Spontaneous, so-called 'conformational' diseases, specially of the neurodegenerative type like Alzheimer's, are linked to certain protein types which have the normal amino-acid sequence but are misfolded and accumulate due to resistance to proteolysis. In the case of prion diseases, the 'protein only' hypothesis assumes that the misconformation of a native protein could be initiated upon interaction with a sister-protein already in the misfolded state. There is an alternative to this sister protein contamination scheme, which assumes that the misconformation is acquired upon protein synthesis, that is de novo. Misfoldling and resistance to proteolysis could result from defects responsible for shortage or inactivity of the cellular factors in charge of protein folding and degradation. The defects could have a genetic origin (the gene of the faulty factor involved could have been mutated, or control and regulation of its expression could have been altered, etc.). Alternatively, the cell's actual biosynthetic and/or proteolytic resources could have become overloaded and unavailable, due to unscheduled mass-production of proteins resulting from unscheduled cell growth or proliferation, cell stress, etc. Xenobiotics, active for instance as endocrine proliferators, stressors, or inducing copious, unscheduled gene expression, etc. could give rise to shortage of cellular factors necessary for the production of native proteins and for proteolysis. Alternatively, xenobiotics could alter expression or activity of some of these factors. In both cases, the xenobiotic could be a 'conformational toxicant' by inducing misfolding of selected proteins. The xenobiotic could trigger some conformational disease if it targets a specific protein and tissue.

Apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, in dopamine neurons.

A dopamine-derived neurotoxin, 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2, 3,4-tetrahydroisoquinoline [N-methyl(R)salsolinol] was found to cause parkinsonian in rats and to deplete selectively dopamine neurons in the substantia nigra after infusion in the striatum. This isoquinoline occurs enantio-specifically in the nigra-striatum of human brains. The biosynthesis from dopamine is catalyzed by two enzymes, (R)salsolinol synthase and (R)salsolinol N-methyltransferase. The isoquinoline increases in the cerebrospinal fluid from parkinsonian patients, and the increase is ascribed to high activity of its synthesizing neutral (R)salsolinol N-methyltransferase, as shown by analyses in lymphocytes. The cell death caused by this neurotoxin in dopaminergic human neuroblastoma SH-SY5Y cells proved to be apoptotic. Apoptosis by this neurotoxin is mediated by intracellular sequential process, loss of mitochondrial membrane potential, activation of caspases and DNA fragmentation. These results are discussed in relation to the role of apoptosis in neurodegenerative diseases and the involvement of the endogenous toxin in the pathogenesis of Parkinson's disease.

Pathogenesis of vascular dementia in stroke-prone spontaneously hypertensive rats.

Stroke-prone spontaneously hypertensive rats (SHRSP) are the best model for essential hypertension and stroke. In this study, one investigated whether SHRSP might be a useful animal model for vascular dementia. An impairment of learning-memory function was found in SHRSP. A disturbance in circadian rhythm after stroke in SHRSP was clarified. Desynchronization of light and dark alternation cycles and abnormal rhythm were also demonstrated. These observations point to the possibility that the decreased passive avoidance response observed in SHRSP might be similar to the phenomenon of memory impairment in patients with vascular dementia. The behavioral changes in ambulation in SHRSP, including the desynchronization between light and dark alternation cycles and the abnormal rhythm before death, might correspond to the behavioral changes associated with the delirium-state observed in patients with dementia. Cerebral cortex levels of acetylcholine and choline in SHRSP decreased significantly as compared with the Wistar Kyoto rats (WKY) control group. Hippocampal levels of acetylcholine and choline in SHRSP decreased significantly as compared with those in WKY. Moreover, a correlation between passive avoidance response latency and hippocampal acetylcholine levels was observed. These findings suggest that decreased acetylcholine levels in both the cerebral cortex and the hippocampus may be related to the impairment of learning-memory function and abnormal behavior. In SHRSP, increases in blood viscosity, hematocrit and fibrinogen might produce the formation of thrombus and induce cerebral infarction. Some histopathological findings caused by cerebrovascular disorder in human brain very similar to those observed in the SHRSP brain. On the other hand, so called 'senile changes' were detected only in the human case, and not observed in the SHRSP.

Animal models of vascular dementia with emphasis on stroke-prone spontaneously hypertensive rats.

1. Two experimental models designed to reflect different aspects of vascular dementia (rats with cerebrovascular occlusion and rats with cerebral embolization) and stroke-prone spontaneously hypertensive rats (SHRSP) have been evaluated. The focus was on SHRSP as a model for vascular dementia. 2. Neuropathological data revealed that the cerebrovascular disorder in SHRSP was associated with lesions in their brains similar to those seen in typical human cases of multiple cerebral infarction. 3. SHRSP that died from cerebral infarction exhibited behavioural changes, including increased activity and disrupted circadian rhythms, which might correspond to the state of delirium observed in patients with dementia. 4. SHRSP displayed cognitive impairments in a step-through passive avoidance task. 5. When compared to age-matched Wistar Kyoto (WKY) rats, both conscious and anaesthetized SHRSP had significantly decreased cerebral spinal fluid (CSF) levels of acetylcholine (ACh). 6. These findings suggest that the SHRSP might serve as a suitable animal model for vascular dementia in humans caused by cerebrovascular lesions.

Inhibition of tryptophan hydroxylase by dopamine and the precursor amino acids.

Effects of dopamine and its precursor amino acids on the activity of tryptophan hydroxylase were examined. They inhibited the enzyme activity prepared from mastocytoma cells in terms of the biopterin cofactor and the substrate L-tryptophan. In relation to the biopterin, tryptophan hydroxylase was found to have two different kinetics, and dopamine inhibited the activity in a non-competitive way to both the components. Dopamine had the highest affinity to the enzyme, followed by L-DOPA and L-tyrosine, while D-tyrosine did not inhibit the activity. In terms of L-tryptophan, L-tyrosine, L-DOPA and dopamine inhibited the enzyme non-competitively and their affinity to the enzyme was in this order. These results indicate that the indoleamine metabolism may be regulated by catecholamines and their related amino acids in the brain.

Phenylethanolamine-N-methyl transferase and catechol-O-methyl transferase activity in rat uterus. Cyclic and steroid-induced changes.

PURPOSE: The activity of phenylethanolamine-N-methyl-transferase (PNMT) and catechol-O-methyl-transferase (COMT) was studied in uterine homogenates from adult female Wistar rats with normal cycles and that had been ovariectomized, adrenalectomized, and steroid-treated. RESULTS: Activities of the two enzymes changed significantly during the normal estrus cycle. Both peaked during metestrus, with COMT showing a secondary peak of activity at proestrus. Progesterone treatment significantly increased and estradiol decreased PNMT activity in comparison to untreated controls. Hydrocortisone administration had no effect on uterine PNMT activity. COMT activity was not affected significantly by any of the steroid treatments. CONCLUSION: The data confirm that uterine tissues possess the enzymatic machinery to synthesize epinephrine from norepinephrine, and suggest the activity of this pathway may be mediated by variations in the sex hormone environment of the uterus.

A genetic and molecular study of learning processes in rats.

Using the conditioned feeding reflex model, a polymorphism for the rate of formation of this response was identified in a population of laboratory animals. Selection for high and low rate of the formation of this reflex resulted in significant differences in this character between two strains by the second generation. These differences were maintained in subsequent generations. Heterogeneity for the rate of the formation of conditioned response in the population is shown to be genetically determined. The RNA-dependent DNA-polymerase activity in the hippocampus of fast-learning rats exceeds twofold that in slow-learning rats, while the rates of the DNA-dependent DNA-polymerase activities are similar. A significant increase in RNA-dependent DNA-polymerase only was found in the hippocampus of rats 20 min after training for the conditioned food response before the trace consolidation registered 40 min after the training session.

Effect of NCO-700, an inhibitor of protease, on lysosomal rupture in the ischemic myocardium.

The effect of NCO-700 (1), a protease inhibitor, on subcellular distribution of lysosomal enzymes was studied in the ischemic perfused rat heart. Ischemia was induced by lowering the afterload pressure of the working heart preparation. The subcellular distribution of lysosomal enzymes was estimated by the ratio of the activities of cathepsin D, beta,N-acetylglucosaminidase, and acid phosphatase in the cytoplasm to the total enzyme activities. Ischemia caused subcellular redistribution of lysosomal enzymes from the lysosomes to the cytoplasm, indicating the rupture of lysosomes. Compound 1 (1.75 x 10(-4) M) was provided for the heart 5 min before the onset of ischemia. Compound 1 appeared to inhibit the rupture of lysosomes being caused by ischemia. The mechanism by which 1 protects the myocardium against ischemic injury may involve the inhibition of lysosomal rupture in the ischemic myocardium.

Characterization of enzymes of catecholamine synthesis and metabolism in human fetal membranes at birth.

We looked for the presence of the enzymes monoamine oxidase, catechol-O-methyltransferase, and phenylethanolamine-N-methyltransferase in human fetal membranes at term. The activity of all three enzymes was detected via highly sensitive and selective radiometric enzyme assays. The most novel finding was the extremely high level of monoamine oxidase activity in the chorion compared with that in the amnion. The other enzyme of catecholamine metabolism, catechol-O-methyltransferase, did not show any difference in activity between the two layers. In addition, we observed that the enzyme phenylethanolamine-N-methyltransferase, which is primarily located in the adrenal medulla, was also present in appreciable levels in the two layers of fetal membranes. These results suggest that fetal membranes, like the placenta, possess the enzymatic machinery to metabolize catecholamines and have the capacity to synthesize epinephrine.

Atrial natriuretic factor: the effects of pregnancy and a high-salt diet on atrial levels.

The chronic and relatively acute changes in blood volume that occur during pregnancy and post partum may be associated with alterations in the content of atrial natriuretic factor in the atria. We measured the concentration of atrial natriuretic factor in the right and left atria of virgin, pregnant, and postpartum Sprague-Dawley rats by radioimmunoassay as well as the concentration of atrial natriuretic factor in the atria and plasma of term pregnant rats on a high-salt diet. Neither right nor left atrial concentrations of atrial natriuretic factor were elevated during pregnancy in animals on a normal diet, but both were increased during the first 2 days after delivery. Term pregnant rats on a high-salt diet showed a small increase in atrial natriuretic factor levels in the left atria only, without any change in plasma atrial natriuretic factor levels. We conclude that relatively acute changes in fluid and electrolyte balance are more likely than chronic ones to be associated with alterations in atrial natriuretic factor concentrations in the atria.

Oxidation of N-methyl-1,2,3,4-tetrahydroisoquinoline into the N-methyl-isoquinolinium ion by monoamine oxidase.

N-Methyl-1,2,3,4-tetrahydroisoquinoline (NMTIQ) was found to be oxidized by monoamine oxidase (MAO) into N-methylisoquinolinium ion, which was proved to inhibit enzymes related to the metabolism of catecholamines, such as tyrosine hydroxylase, aromatic-L-amino acid decarboxylase, and MAO. NMTIQ was oxidized by both types A and B MAO in human brain synaptosomal mitochondria. Oxidation was dependent on the amount of MAO sample and the reaction time. Enzyme activity with respect to NMTIQ reached optimum at a pH of approximately 7.25, as was the case with other substrates. Type A MAO had higher activity for this substrate than type B. The Km and Vmax values of the oxidation by types A and B MAO were 571 +/- 25 microM and 0.29 +/- 0.06 pmol/min/mg protein, and 463 +/- 43 microM and 0.16 +/- 0.03 pmol/min/mg protein, respectively. The Vmax values of types A and B MAO for NMTIQ were much smaller than those for other substrates such as kynuramine. NMTIQ was the first tetrahydroisoquinoline shown to be oxidized into the isoquinolinium ion by MAO in the brain.

Plasma atrial natriuretic peptide levels during the rat estrous cycle, pregnancy, and puerperium.

The rat has been used as a model for studying the changes that occur in maternal blood volume and renal function during pregnancy. The role, if any, that atrial natriuretic peptide plays in regulating these changes is unknown, and little information is available on atrial natriuretic peptide levels at different stages of gestation in the rat. In this study we measured plasma atrial natriuretic peptide levels by radioimmunoassay in the rat at each stage of the estrous cycle, during the last 2 weeks of pregnancy, and in the early postpartum period. Atrial natriuretic peptide levels did not change during the estrous cycle. Atrial natriuretic peptide levels were low on days 10 to 15 of gestation but rose to become significantly higher than nonpregnant levels on days 16 to 18. On day 21 shortly before delivery, levels were similar to nonpregnant values. Postpartum, atrial natriuretic peptide levels rose immediately and remained elevated for the next 48 hours. These findings suggest that factors other than blood volume may mediate plasma atrial natriuretic peptide levels during pregnancy and the postpartum period.

N-methylisoquinolinium ion as an inhibitor of tyrosine hydroxylase, aromatic l-amino acid decarboxylase and monoamine oxidase.

The effect of the N-methylisoquinolinium ion (NMIQ(+)) on the activity of enzymes related to metabolism of dopamine was studied using a rat clonal pheochromocytoma PC12h cell line. The activities of tyrosine hydroxylase (TH), aromatic l-amino acid decarboxylase (AADC) and monoamine oxidase (MAO) were inhibited by NMIQ(+), but the mechanism of inhibition of these enzymes differed from each other. TH activity in the cells was inhibited by NMIQ(+) with an IC(50) of about 75 ?M. Aromatic l-amino acid decarboxylase (AADC) was also inhibited by NMIQ(+) but in competition with a co-factor, pyridoxal-5-phosphate, and the K(i) value was 90 ?M. MAO was inhibited by NMIQ(+) in competition with a substrate, kynuramine, and the K(i) value was 20 ?M. In vivo effects of NMIQ(+) on these enzymes in PC12h cells were examined by culture of the cells in the presence of 100 nM-1 mM NMIQ(+) for 6 days. After 6 days culture, TH activity was reduced in cells cultured with NMIQ(+) at concentrations higher than 10 ?M, but the activities of AADC and MAO were reduced only in cells cultured with 1 mM NMIQ(+). In addition, NMIQ(+) was transported into the cells by a transport system specific for dopamine. These data suggest that NMIQ(+) may perturb the catecholamine metabolism of a dopaminergic system in the brain, as a naturally-occurring compound.