Central hemodynamic effects of adrenaline with special reference to beta 2-adrenergic influence on heart rate and cardiac afterload in anesthetized cats

Central hemodynamic responses evoked by i.v. infusions of adrenaline and noradrenaline were studied in normovolemic anesthetized cats with intact adrenoceptors, after selective beta 2-blockade (ICI 118,551), and after nonselective beta-blockade propranolol). The results demonstrated the presence of an important beta 2-adrenergic component in the integrated response to 'physiological' doses of adrenaline contributing to increased cardiac output, decreased total peripheral resistance and virtually unchanged mean arterial blood pressure. Corresponding beta 2-adrenergic effects of noradrenaline were small. The beta 2-adrenergic effects of adrenaline on the heart seemed to be both direct and indirect. A moderate direct chronotropic response mediated by beta 2-adrenoceptors apparently was present but there was no evidence of a direct beta 2-adrenergic inotropic effect. An indirect, quite marked effect on the heart was accomplished by a beta 2-adrenergic vasodilator interaction with the alpha-adrenergic vasoconstrictor influence on the systemic resistance vessels. This caused a net decrease in total peripheral resistance, thereby preventing an undue increase in cardiac afterload (arterial pressure) which seemed to be essential for evoking 'optimal' increases in cardiac output. It is suggested that such adrenaline evoked indirect, beta 2-adrenergic improvement of cardiac performance is of functional importance in reflex sympatho-adrenal circulatory control.     

Activation of mucosal Vβ3+ T cells and tissue damage in human small intestine by the bacterial superantigen,Staphylococcus aureus enterotoxin B

Staphylococcus aureus enterotoxin B (SEB) was added to explants of fetal human intestine in organ culture or administered into the lumen of fetal small intestine prior to culture. Both routes produced a massive increase in lamina propria T cells expressing Vβ33, and to a lesser extent, those expressing Vβ5 and Vβ12. SEB-activated lamina propria T cells produced interleukin-2 and interferon-Y and T cell activation was accompanied by tissue damage, which was inhibited by FK506.     

Developmental changes in release properties of the CA3-CA1 glutamate synapse in rat hippocampus

Developmental changes in release probability (Pr) and paired-pulse plasticity at CA3-CA1 glutamate synapses in hippocampal slices of neonatal rats were examined using field excitatory postsynaptic potential (EPSP) recordings. Paired-pulse facilitation (PPF) at these synapses was, on average, absent in the first postnatal week but emerged and became successively larger during the second postnatal week. This developmental increase in PPF was associated with a reduction in Pr, as indicated by the slower progressive block of the N-methyl-D-aspartate (NMDA) EPSP by the noncompetitive NMDA receptor antagonist MK-801. This developmental reduction in Pr was not homogenous among the synapses. As shown by the MK-801 analysis, the Pr heterogeneity observed among adult CA3-CA1 synapses is present already during the first postnatal week, and the developmental Pr reduction was found to be largely selective for synapses with higher Pr values, leaving Pr of the vast majority of the synapses essentially unaffected. A reduction in Pves, the release probability of the individual vesicle, possibly caused by reduction in Ca2+ influx, seems to explain the reduction in Pr. In vivo injection of tetanus toxin at the end of the first postnatal week did not prevent the increase in PPF, indicating that this developmental change in release is not critically dependent on normal neural activity during the second postnatal week.     

Changes in bone turnover during tibolone treatment

OBJECTIVES: An open study was carried out to evaluate changes in bone remodeling markers such as N-telopeptide (NTx), tartrate-resistant acid phosphatase (TRAP), total alkaline phosphatase (TAP), and bone alkaline phosphatase (BAP) during a 1-year continuous tibolone treatment in postmenopausal women. MATERIAL AND METHODS: Thirty-six postmenopausal women were recruited for receiving tibolone 2.5 mg per day for 1 year. Densitometry and determination of biochemical markers of bone metabolism in serum and urine were performed at 1, 3, 6, and 12 months. RESULTS: Comparing baseline with 12 month's values, BAP and all resorption markers decreased significantly. NTx began to decrease since the initiation of the treatment (baseline: 74.4 +/- 5.3; 1 month: 57.5 +/- 4.2; 12 months: 36.6 +/- 2.8). BAP increased at the first month (baseline: 37.3 +/- 2.1; 1 month: 42.6 +/- 3.0) but diminished in the following months (12 months: 23.1 +/- 1.5). TAP started to decrease significantly only after 6 months of treatment (baseline: 37.3 +/- 2.1; 12 months: 31.4 +/- 2.3) and TRAP after 3 months (baseline: 9.8 +/- 0.4; 6 months: 9.1 +/- 0.5; 12 months: 8.2 +/- 0.4). Normal bone mineral density at distal and ultradistal forearm was maintained during the 1-year treatment (baseline: 0.42 +/- 0.01; 12 months: 0.42 +/- 0.01 and baseline: 0.33 +/- 0.01; 12 months: 0.33 +/- 0.01, respectively). CONCLUSION: The use of tibolone 2.5 mg per day diminished progressively and significantly bone resorption and formation markers during 1-year treatment period.     

Neurotensin modulates the binding characteristics of dopamine D2 receptors in rat striatal membranes also following treatment with toluene

The effects of neurotensin in vitro (1-100 nM) on the binding characteristics of [3H]N-propylnorapomorphine ([3H]NPA) were analysed in striatal membrane preparations of the adult male rat. Subsequently, it was investigated whether the modulatory effects of 10 nM neurotensin on [3H]NPA binding were altered by treatment with toluene in vivo (80 p.p.m., 3 days, 6 h day-1) and in vitro (19 mumol ml-1). Displacement of [3H]NPA binding by raclopride (IC50 about 15 nM) and SCH 23390 (without effect) indicated that [3H]NPA labelled only D2 dopamine receptors in the present study. Neurotensin was found to reduce the affinity of D2 receptors with a maximum response at 10 nM. At this concentration the KD value was increased by 30-40% without any consistent changes in the number of binding sites. The modulatory effect of neurotensin remained intact also following toluene treatment in vivo and in vitro, although at a higher KD range, since toluene alone increased the KD value of [3H]NPA binding by 40-50%. Thus, the mechanisms mediating the effects of neurotensin and toluene on the D2 receptor are likely to be different. When neurotensin and toluene treatments were combined, the KD values of [3H]NPA binding were about twice as high as in non-treated controls. These additive effects may lead to a severely decreased efficiency of dopamine D2-mediated neurotransmission in vivo.     

Activity-dependent control of bulk endocytosis by protein dephosphorylation in central nerve terminals

Bulk endocytosis is the process by which nerve terminals retrieve large amounts of synaptic vesicle membrane during periods of strong stimulation intensity. The process is rapidly activated and is most probably calcium dependent in a similar manner to synaptic vesicle exocytosis. This article briefly summarizes the current knowledge of bulk endocytosis with respect to its activation, kinetics and molecular mechanism. It also presents recent data from our laboratory showing that the dephosphorylation of a group of endocytosis proteins called the dephosphins by the Ca²⁺-dependent protein phosphatase calcineurin is key to the activity-dependent stimulation of the process. Possible downstream effectors of calcineurin are discussed such as the large GTPase dynamin I and its phosphorylation-dependent interaction partner syndapin I.     

Effect of Down syndrome on the dimensions of dental crowns and tissues

Abnormal growth in Down syndrome (DS) is reflected by variable reduction in size and simplification in form of many physical traits. This study aimed to compare the thickness of enamel and dentine in deciduous and permanent mandibular incisor teeth between DS and non‐DS individuals and to clarify how these tissues contribute to altered tooth size in DS. Sample groups comprised 61 mandibular incisors (29 permanent and 32 deciduous) from DS individuals and 55 mandibular incisors (29 permanent and 26 deciduous) from non‐DS individuals. Maximum mesiodistal and labiolingual crown dimensions were measured initially, then the crowns were sectioned midsagittally and photographed using a stereomicroscope. Linear measurements of enamel and dentine thickness were obtained on the labial and lingual surfaces of the crowns, together with enamel and dentine–pulp areas and lengths of the dentino‐enamel junction. Reduced permanent crown size in DS was associated with a reduction in both enamel and dentine thickness. After adjustments were made for tooth size, DS permanent incisors had significantly thinner enamel than non‐DS permanent teeth. The DS permanent teeth also exhibited significant differences in shape and greater variability in dimensions than the non‐DS permanent teeth. Crown dimensions of deciduous incisors were similar in size or larger in DS compared with non‐DS deciduous teeth. Enamel and dentine thicknesses of the deciduous teeth were similar in DS and non‐DS individuals. The findings indicate that growth retardation in DS reduces both enamel and dentine deposition in the permanent incisors but not in the earlier‐forming deciduous predecessors. The results are also consistent with the concept of amplified developmental instability for dental traits in DS. Am. J. Hum. Biol. 13:690–698, 2001. © 2001 Wiley‐Liss, Inc.