Vascular anomaly - left anterior descending artery originating from right coronary sinus

A case of a patient with congenital anomaly of coronary blood vessels with left anterior descending artery starting from right coronary sinus is presented. The patient was operated on due to symptoms of myocardial ischaemia by carrying out an off-pump coronary artery bypass graft to left anterior descending artery and obtuse marginal artery, with a very good outcome.     

Small-molecule agonists for the glucagon-like peptide 1 receptor

The peptide hormone glucagon-like peptide (GLP)-1 has important actions resulting in glucose lowering along with weight loss in patients with type 2 diabetes. As a peptide hormone, GLP-1 has to be administered by injection. Only a few small-molecule agonists to peptide hormone receptors have been described and none in the B family of the G protein coupled receptors to which the GLP-1 receptor belongs. We have discovered a series of small molecules known as ago-allosteric modulators selective for the human GLP-1 receptor. These compounds act as both allosteric activators of the receptor and independent agonists. Potency of GLP-1 was not changed by the allosteric agonists, but affinity of GLP-1 for the receptor was increased. The most potent compound identified stimulates glucose-dependent insulin release from normal mouse islets but, importantly, not from GLP-1 receptor knockout mice. Also, the compound stimulates insulin release from perfused rat pancreas in a manner additive with GLP-1 itself. These compounds may lead to the identification or design of orally active GLP-1 agonists.     

Intraneuronal Aβ immunoreactivity is not a predictor of brain amyloidosis-β or neurofibrillary degeneration

Amyloid β (Aβ) immunoreactivity in neurons was examined in brains of 32 control subjects, 31 people with Down syndrome, and 36 patients with sporadic Alzheimer’s disease to determine if intraneuronal Aβ immunoreactivity is an early manifestation of Alzheimer-type pathology leading to fibrillar plaque formation and/or neurofibrillary degeneration. The appearance of Aβ immunoreactivity in neurons in infants and stable neuron-type specific Aβ immunoreactivity in a majority of brain structures during late childhood, adulthood, and normal aging does not support this hypothesis. The absence or detection of only traces of reaction with antibodies against 4–13 aa and 8–17 aa of Aβ in neurons indicated that intraneuronal Aβ was mainly a product of α- and γ-secretases (Aβ_17–40/42). The presence of N-terminally truncated Aβ_17–40 and Aβ_17–42 in the control brains was confirmed by Western blotting and the identity of Aβ_17–40 was confirmed by mass spectrometry. The prevalence of products of α- and γ -secretases in neurons and β- and γ-secretases in plaques argues against major contribution of Aβ-immunopositive material detected in neuronal soma to amyloid deposit in plaques. The strongest intraneuronal Aβ_17–42 immunoreactivity was observed in structures with low susceptibility to fibrillar Aβ deposition, neurofibrillary degeneration, and neuronal loss compared to areas more vulnerable to Alzheimer-type pathology. These observations indicate that the intraneuronal Aβ immunoreactivity detected in this study is not a predictor of brain amyloidosis or neurofibrillary degeneration. The constant level of Aβ immunoreactivity in structures free from neuronal pathology during essentially the entire life span suggests that intraneuronal amino-terminally truncated Aβ represents a product of normal neuronal metabolism. This study was supported in part by funds from the New York State Office of Mental Retardation and Developmental Disabilities and grants from the National Institutes of Health (The National Institute of Child Health and Human Development R01 HD43960 and PO1 HD35897; and the National Institute of Aging P30 AG08051, AG03051, and PO1 AG11531).     

The role of overexpressed DYRK1A protein in the early onset of neurofibrillary degeneration in Down syndrome

The gene encoding the minibrain kinase/dual-specificity tyrosine phosphorylated and regulated kinase 1A (DYRK1A) is located in the Down syndrome (DS) critical region of chromosome 21. The third copy of DYRK1A is believed to contribute to abnormal brain development in patients with DS. In vitro studies showing that DYRK1A phosphorylates tau protein suggest that this kinase is also involved in tau protein phosphorylation in the human brain and contributes to neurofibrillary degeneration, and that this contribution might be enhanced in patients with DS. To explore this hypothesis, the brain tissue from 57 subjects including 16 control subjects, 21 patients with DS, and 20 patients with sporadic Alzheimer's disease (AD) was examined with two antibodies to the amino-terminus of DYRK1A (7F3 and G-19), as well as two polyclonal antibodies to its carboxy-terminus (X1079 and 324446). Western blots demonstrated higher levels of full-length DYRK1A in the brains of patients with DS when compared to control brains. Immunocytochemistry revealed that DYRK1A accumulates in neurofibrillary tangles (NFTs) in subjects with sporadic AD and in subjects with DS/AD. Overexpression of DYRK1A in patients with DS was associated with an increase in DYRK1A-positive NFTs in a gene dosage-dependent manner. Results support the hypothesis that overexpressed DYRK1A contributes to neurofibrillary degeneration in DS more significantly than in subjects with two copies of the DYRK1A gene and sporadic AD. Immunoreactivity with antibodies against DYRK1A not only in NFTs but also in granules in granulovacuolar degeneration and in corpora amylacea suggests that DYRK1A is involved in all three forms of degeneration and that overexpression of this kinase may contribute to the early onset of these pathologies in DS.     

Aerobic–anaerobic transition intensity measured via EMG signals in athletes with different physical activity patterns

The purpose of the present study was to investigate the use of electromyographic signals (EMG), to determine the EMG threshold (EMGT) in four lower extremity muscles and to compare these thresholds with the second ventilatory threshold (VT2) in subjects participating in different sports and at different performance levels. Forty-nine subjects (23.8 ± 5.7 years, 182.7 ± 5.3 cm, 79.1 ± 8.6 kg) including eleven cyclists, ten team-handball players, nine kayakers, eight power lifters and eleven controls were investigated utilizing a cycle ergometer. Respiratory gas exchange measures were collected and EMG activity was continuously recorded from four muscles (vastus lateralis, vastus medialis, biceps femoris and gastrocnemius lateralis). The VO₂max averaged 56.1 ± 11.1 ml kg⁻¹ min⁻¹, the average aerobic power was 348.5 ± 61.0 W and the corresponding VT2 occurred at 271.4 ± 64.0 W. The EMGT ranged from 80 to 98% of power output for the different muscles. The VT2 and EMG thresholds from four different muscles were not different. When thresholds were analyzed among different groups of subjects, no significant difference was observed between VT2 and EMGT despite threshold differences between the groups. All four EMGT were significantly related to maximal aerobic power (r = 0.73–0.83) and were highly correlated to each other (r = 0.57–0.88). In conclusion, EMGT can be used to determine the VT2 for individuals independent of sport specificity or performance level.