Aspartame—True or False? Narrative Review of Safety Analysis of General Use in Products

Aspartame is a sweetener introduced to replace the commonly used sucrose. It was discovered by James M. Schlatter in 1965. Being 180–200 times sweeter than sucrose, its intake was expected to reduce obesity rates in developing countries and help those struggling with diabetes. It is mainly used as a sweetener for soft drinks, confectionery, and medicines. Despite its widespread use, its safety remains controversial. This narrative review investigates the existing literature on the use of aspartame and its possible effects on the human body to refine current knowledge. Taking to account that aspartame is a widely used artificial sweetener, it seems appropriate to continue research on safety. Studies mentioned in this article have produced very interesting results overall, the current review highlights the social problem of providing visible and detailed information about the presence of aspartame in products. The studies involving the impact of aspartame on obesity, diabetes mellitus, children and fetus, autism, neurodegeneration, phenylketonuria, allergies and skin problems, its cancer properties and its genotoxicity were analyzed. Further research should be conducted to ensure clear information about the impact of aspartame on health.     

Open reduction,Dega osteotomy and proximal femoral osteotomy in delayed diagnosis of developmental hip dislocation: outcome at 40-year follow-up

PurposeLate-diagnosed dislocated hips underwent open reduction, Dega osteotomy, and proximal femoral osteotomy between 1968 and 1988. The objectives of this study are to assess the survival of hips into adulthood, clinical and radiological outcome, patients’ life perspectives and the risk factors of failure.MethodsAn assessment of 67 hips treated when younger than five years (<age 5yr. group) and 71 hips in the group aged older than five years (+age 5yr.) was performed. All cases were evaluated clinically and radiographically, and survival was assessed, considering hip replacement as endpoints for failure (abbreviation HR+ refers to hips that underwent hip replacement surgery; HR- refers to hips that have not been replaced at the follow-up). The fertility rate and the social security disability benefits (SSDB) recipiency percentage were calculated.ResultsThe 40-year survival rates were 73% (95% confidence (CI) 71% to 76%) in the <age 5yr. group, 54% (95% CI 51% to 57%) in the +age 5yr. group, 70% (95% CI 67% to 73%) in one-sided dislocations and 57% (95% CI 54% to 60%) in bilateral dislocations. At follow-up, the median Harris hip and Western Ontario and McMaster Universities Osteoarthritis scores were 90.0 and 13.0 (<age 5yr. group, HR-), 74.0 and 28.0 (+age 5yr. group, HR-), 90.0 and 16.0 (<age 5yr. group, HR+) and 84.5 and 11.5 (+age 5yr. group, HR+), respectively. The operation normalized the radiological parameters. The correlation between the grade of femoral head avascular necrosis (AVN) at a median 2.6 years after the operation and the grade of osteoarthritis at follow-up was 0.38 (p < 0.001). The fertility rate was 1.54. In total, 16.0% (aged under five years) and 38.5% (aged over five years) of patients were receiving SSDB (p = 0.003).ConclusionEarly failure risk factors are older age at the surgical procedure, high AVN grade and bilateral hip involvement. Still, the results facilitate hip reposition whenever technically manageable, even in teenagers.Level of evidenceIII     

Selective inhibitors of glial GABA uptake: synthesis, absolute stereochemistry, and pharmacology of the enantiomers of 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole (exo-THPO) and analogues

3-Methoxy-4,5,6,7-tetrahydro-1,2-benzisoxazol-4-one (20a), or the corresponding 3-ethoxy analogue (20b), and 3-chloro-4,5,6, 7-tetrahydro-1,2-benzisothiazol-4-one (51) were synthesized by regioselective chromic acid oxidation of the respective bicyclic tetrahydrobenzenes 19a,b and 50, and they were used as key intermediates for the syntheses of the target zwitterionic 3-isoxazolols 8-15 and 3-isothiazolols 16 and 17, respectively. These reaction sequences involved different reductive processes. Whereas (RS)-4-amino-3-hydroxy-4,5,6,7-tetrahydro-1,2-benzisoxazole (8, exo-THPO) was synthesized via aluminum amalgam reduction of oxime 22a or 22b, compounds 9, 11-13, and 15-17 were obtained via reductive aminations. Compound 10 was synthesized via N-ethylation of the N-Boc-protected primary amine 25. The enantiomers of 8 were obtained in high enantiomeric purities (ee >/= 99.1%) via the diastereomeric amides 32 and 33, synthesized from the primary amine 23b and (R)-alpha-methoxyphenylacetyl chloride and subsequent separation by preparative HPLC. The enantiomers of 9 were prepared analogously from the secondary amine 27. On the basis of X-ray crystallographic analyses, the configuration of oxime 22a was shown to be E and the absolute configurations of (-)-8 x HCl and (+)-9 x HBr were established to be R. The effects of the target compounds on GABA uptake mechanisms in vitro were measured using a rat brain synaptosomal preparation and primary cultures of mouse cortical neurons and glia cells (astrocytes). Whereas the classical GABA uptake inhibitor, (R)-nipecotic acid (2), nonselectively inhibits neuronal (IC(50) = 12 microM) and glial (IC(50) = 16 microM) GABA uptake and 4,5,6,7-tetrahydroisoxazolo?4,5-cpyridin-3-ol (1, THPO) shows some selectivity for glial (IC(50) = 268 microM) versus neuronal (IC(50) = 530 microM) GABA uptake, exo-THPO (8) was shown to be more potent as an inhibitor of glial (IC(50) = 200 microM) rather than neuronal (IC(50) = 900 microM) GABA uptake. This selectivity was more pronounced for 9, which showed IC(50) values of 40 and 500 microM as an inhibitor of glial and neuronal GABA uptake, respectively. These effects of 8 and 9 proved to be enantioselective, (R)-(-)-8 and (R)-(+)-9 being the active inhibitors of both uptake systems. The selectivity of 9 as a glial GABA uptake inhibitor was largely lost by replacing the N-methyl group of 9 by an ethyl group, compound 10 being an almost equipotent inhibitor of glial (IC(50) = 280 microM) and neuronal (IC(50) = 400 microM) GABA uptake. The remaining target compounds, 11-17, were very weak or inactive as inhibitors of both uptake systems. Compounds 9-13 and 15 were shown to be essentially inactive against isoniazide-induced convulsions in mice after subcutaneous administration. The isomeric pivaloyloxymethyl derivatives of 9, compounds 43 and 44, were synthesized and tested as potential prodrugs in the isoniazide animal model. Both 43 (ED(50) = 150 micromol/kg) and 44 (ED(50) = 220 micromol/kg) showed anticonvulsant effects, and this effect of 43 was shown to reside in the (R)-(+)-enantiomer, 45 (ED(50) = 44 micromol/kg). Compound 9 also showed anticonvulsant activity when administered intracerebroventricularly (ED(50) = 59 nmol).     

Clonidine-induced locomotor hyperactivity in rats

Summary The -adrenergic agonist, clonidine, causes sedation in normal rats. The present study demonstrates that clonidine evokes strong locomotor stimulation in rats pretreated with 6-hydroxydopamine plus reserpine. Similar, but less intensive hyperactivity is observed in rats given clonidine after combined pretreatment with 6-hydroxydopamine plus p-chlorophenylalanine plus -methyl-p-tyrosine, or with reserpine plus low doses of yohimbine. The -adrenolytic drugs, phenoxybenzamine, phentolamine and aceperone, as well as high doses of yohimbine, antagonise the clonidine-induced locomotor stimulation; in contrast, the dopamine receptor blocking agents, pimozide and spiroperidol, exert no antagonistic effect. The results indicate that in the brain of normal animals, clonidine predominantly activates presynaptic -adrenoceptors on noradrenergic neurones and thereby induces sedation. After destruction of the noradrenergic fibres by 6-hydroxydopamine plus reserpine, activation of postsynaptic -adrenoceptors prevails so that hyperactivity results.This study was supported by Polish Academy of Sciences (10.4). Preliminary accounts were presented at the Pharmacology Meeting, Hannover, September 14–17, 1976 and at the 1 st Joint Symposium of Hungarian and Polish Pharmacological Societies, Zakopane, October, 13–15, 1976     

Assessment of blood flow velocity during cognitive stimulation in persons with suspected hydrocephalus

The aim of this work is to evaluate middle cerebral arteries (MCA) blood flow velocity changes during performance of linguistic and visuospatial cognitive tasks. Two groups were investigated: eight patients with suspected hydrocephalus without perceptible cognitive disturbances, and eight healthy persons. Blood flow velocity in left and right MCA was recorded with transcranial Doppler sonography while the examined patients were performing three different tasks. The analysis of the results showed differences between the groups concerning both increase of blood flow velocity values and performance patterns. Compared to healthy individuals less increase in blood flow velocity during performance of all tasks and no difference in haemodynamic changes between both hemispheres during task performance were observed in patients with hydrocephalus. The results obtained suggest, that the pattern of functional lateralization in brain in patients with suspected hydrocephalus is probably changed.     

Effect of Transmural Extent of the Simulated Infarction in a Left Ventricular Model on Displacement and Strain Distribution Estimated from Synthetic Ultrasonic Data

The identification of a sub-endocardial infarction is of major interest in cardiology. This study evaluates the sensitivity of selected measures to the thickness of such an infarction. Synthetic ultrasonic data (long-axis view) of left ventricular models with inclusions were generated using Field II and meshes obtained from finite-element simulations, which also provided the reference for the estimates obtained from ultrasonic data. The displacements, the first and second component of the principal strain (ε₁ and ε₂), and several measures derived from these quantities were estimated. All estimates, except for the poorly estimated ε₂, exhibited sensitivity to the presence and transmurality of the inclusion. The most sensitive was the gradient of the averaged transmural profiles of ε₁, and ε₁ averaged over the area corresponding to the transmural inclusion. The inflection point of the ε₁ profile shifted toward the outer wall with increasing thickness of the non-transmural inclusion.     

Accumulation of Cadmium in and Its Effect on the Midgut Gland of Terrestrial Snail Helix pomatia L. from Urban Areas in Poland

The objectives of this study were (1) to determine cadmium (Cd) accumulation in the midgut gland of a land snail Helix pomatia L. inhabiting residential areas of the 14 largest cities in Poland, and (2) to examine whether the accumulated Cd exerted any toxic effects. The average accumulation of Cd in the midgut gland of snails, weighing 16–18 g, ranged from 7.00 to 87.3 µg/g dry weight (0.06–0.77 µmol/g) and differed significantly among animals from the various urban areas. This difference in Cd accumulation was not related to city population, but was associated with the topsoil Cd (R² = 0.868, p < 0.0001). The tissue Cd was not found to produce toxicity (histopathology, programmed cell death, lipofuscin formation or lipid peroxidation), probably due to the induction of sufficiently high quantities of metallothionein and glutathione, well-known protective molecules.