Morphologic evaluation of the liver in hereditary angioedema patients on long-term treatment with androgen derivatives

17 alpha-Alkylated androgens are highly effective in preventing attacks in HAE patients. These drugs, however, seem to be implicated in the development of cholestatic jaundice, peliosis hepatis, and liver tumors. In order to assess the risk-benefit balance of the long-term therapy with androgen derivatives, a follow-up investigation was performed in 13 HAE patients. The results of this study indicate that long-term treatment (15 to 47 mo) with low doses of danazol or stanozolol does not induce significant hepatic damage detectable by laboratory tests or liver biopsy. However, the limited number of patients, although in a rather long period of observation, still suggests a careful control and the use of minimal effective doses.     

Role of potassium in the regulation of systemic physiological function during exercise

In exercise, potassium (K⁺) is released from contracting muscle predominately through K⁺ channels associated with the repolarization phase of the action potential. Increases in extracellular K⁺ are directly related to increases in metabolic rate and may reach concentrations as high as 8–9 mm in the arterial blood during exhaustive work. Exercise-induced hyperkalaemia has been implicated in several physiological processes, in particular skeletal muscle fatigue, hyperaemia, pressor reflex, arterial chemosensitivity and myocardial stability. There is no direct evidence to show that hyperkalaemia causes muscle fatigue, although raised extracellular [K⁺] may contribute to fatigue during prolonged tetani by depressing the propagation of the action potential down the t-tubule system, thus impairing the release of Ca²⁺ from the sarcoplasmic reticulum. The vasodilating properties of K⁺ may transiently contribute to the early phase of exercise hyperaemia and interact synergistically with other vasoactive substances to cause relaxation by hyperpolarizing K⁺ channels in vascular smooth muscle. Hyperkalaemia has been implicated in the regulation of arterial blood pressure through activation of the muscle afferent reflex where potassium-depolarized C fibres may contribute to a reflex increase in arterial blood pressure. K⁺ can also increase ventilation and the sensitivity of the ventilatory response to hypoxia through direct excitation of the arterial chemoreceptors. Finally, to maintain myocardial electrical stability in exercise, there is a beneficial interaction between raised K⁺ and catecholamines on the heart, so that when they combine, each offsets the other's deleterious effects.     

黑尾蜡嘴雀原纹状体发声控制核团的传入性纤维联系

将HRP微电泳人黑尾蜡嘴雀(Eophona mihratoria)端脑原纹状体粗核内,观察其传入性纤维联系.在下列部位发现有密集的逆行标记细胞:(1):原纹状体带核;(2)上纹状体腹侧尾核;(3)新纹状体前部大细胞核外侧部;(4)脑桥蓝斑.以上标记细胞均出现在同侧.结果表明,原纹状体粗核接受原纹状体带核、上纹状体腹侧尾核、新纹状体前部大细胞核外侧部及脑桥蓝斑的传入性投射.     

Near‐infrared spectroscopy determined brain and muscle oxygenation during exercise with normal and resistive breathing

To elevate effects of carbon dioxide (CO₂) retention by way of an increased respiratory load during submaximal exercise (150 W), the concentration changes of oxy‐ (ΔHbO₂) and deoxy‐haemoglobin (ΔHb) of active muscles and the brain were determined by near‐infrared spectroscopy (NIRS) in eight healthy males. During exercise, pulmonary ventilation increased to 33 (28–40) L min^–1 (median with range) with no effect of a moderate breathing resistance (reduction of the pneumotach diameter from 30 to 14 and 10 mm). The end‐tidal CO₂ pressure (P_ETCO ₂) increased from 45 (42–48) to 48 (46–58) mmHg with a reduction of only 1% in the arterial haemoglobin O₂ saturation (S_aO ₂). During control exercise (normal breathing resistance), muscle and brain ΔHbO₂ were not different from the resting levels, and only the leg muscle ΔHb increased (4 (–2–10) μM , P < 0.05). Moderate resistive breathing increased ΔHbO₂ of the intercostal and vastus lateralis muscles to 6 ± (–5–14) and 1 (–7–9) μM (P < 0.05), respectively, while muscle ΔHb was not affected. Cerebral ΔHbO₂ and ΔHb became elevated to 6 (1–15) and 1 (–1–6) μM by resistive breathing (P < 0.05). Resistive breathing caused an increased concentration of oxygenated haemoglobin in active muscles and in the brain. The results indicate that CO₂ influences blood flow to active skeletal muscle although its effect appears to be smaller than for the brain.     

Haemodynamic Adjustments to Mental Stress in Normotensives and Subjects with Mildly Elevated Blood Pressure

Cardiac output, heart rate, stroke volume, pre-ejection period, total peripheral resistance, systolic and diastolic blood pressure, and oxygen consumption were monitored or derived in young men with mildly elevated casual blood pressures and unambiguously normotensive control subjects before, during, and after exposure to a mental arithmetic stress. Measurements were also taken while subjects underwent graded dynamic exercise. This permitted cardiac output-oxygen consumption regression equations to be calculated and, as a consequence, cardiac output during mental stress to be represented as additional cardiac output. Systolic and diastolic blood pressure were higher during all phases of the study in the mildly elevated blood pressure group. An overall groups effect during the mental stress phase of the experiment was observed for cardiac output and pre-ejection period, and the effect for stroke volume was close to significance. Significant Groups X Periods interactions were found for cardiac output and additional cardiac output, and the heart rate effect was nearly significant. Post-hoc comparisons here indicated that, in the main, group differences in these cardiac variables were more evident during the mental arithmetic stress than during the pre- and post-task baseline periods. Total peripheral resistance did not differ reliably between groups and the cardiac effects were specific to the mental stress phase of the study.     

Intraocular grafting of cultured brain tissue: growth, vascularization and neuron survival in locus coeruleus and cortex cerebri

Locus coeruleus and cortex cerebri from embryonic (ED 17) and newborn rats were kept 4 days in tissue culture under conditions maintaining organotypic features and then transplanted to the anterior chamber of the eye of adult rats. Vascularization from the host iris was delayed in pre-cultured grafts as compared to directly grafted material. In spite of this, several morphological parameters developed normally. Thus, pre-cultured grafts grew considerably in oculo. Falck-Hillarp histochemistry showed that grafts of cortex cerebri received an adrenergic innervation from the host iris and that locus coeruleus grafts contained central adrenergic neurons capable of innervating a sympathetically denervated host iris. The successful combination of tissue culture and intraocular transplantation should permit the selective advantages of both techniques to be applied to the same tissue pieces, generating new information unobtainable by either method alone.     

Hyperpolarization of hypothalamic parvocellular neurons by 17 β-estradiol and their identification through intracellular staining with procion yellow

Summary Intracellular recordings and injections of procion yellow (PY) were made in parvocellular neurons in hypothalamic slices of female guinea pigs. Eighty-five neurons, with an average resting membrane potential of -35 mV, were recorded in the arcuate (ARC) ventromedial (VM), and in the cellpoor zones between the ARC and VM. Eleven of the ARC neurons and four neurons from the cell-poor zone could be driven antidromically by median eminence (ME) stimulation, nine other neurons from the three areas could be driven orthodromically by stria terminalis (ST) stimulation.Twenty-eight parvocellular neurons were tested with 17 -estradiol (E₂), which was applied in the bathing medium as the free steroid. Eleven neurons (nine ARC and two cell-poor-zone neurons) were hyperpolarized 2 to 24 mV by 10^–10 M E₂ concentrations. 10^–8 M estrone concentration was without effect on three of these cells. Through the intracellular injection of PY, the estrogen-sensitive neurons (N = 11) were identified as small fusiform cells with few dendrites. Spine-like appendages were found on only one of these cells. None of the larger pyramidal-like neurons of these areas responded to the application of E₂.Postdoctoral research fellow of the National Institute of Neurological and Communicative Disorders and Stroke     

Tissue temperature oscillations in an isolated pig kidney during surface heating

In the present study, an isolated pig kidney was used to study tissue temperature oscillations due to vascular thermoregulation, frequently observed during hyperthermia treatments. The kidney was perfused with the distilled water pumped through the renal artery to simulate blood flow. When the local perfusion rate was increased with a time delay, temperature oscillations were observed in the kidney as its surface temperature raised linearly with time in a water bath. The magnitude of tissue temperature decreased as the flow rate increased during the surface heating. A 3D transient model was developed to predict the temperature oscillations, which was validated by the measurements. Using the model, relationships of the changes in perfusion rate and heating rate with temperature oscillations were investigated. It was found that the heating rate, and the magnitude and time delay of the flow response to the temperature elevation, each significantly affected tissue temperature oscillations. The magnitude of oscillation was primarily determined by the spatial gradient of temperature, while the oscillation type depended on the change of flow rate and the time delay. In conclusion, to accurately predict and control the tissue temperature distribution during hyperthermia treatment, understanding of the local perfusion change with respect to tissue temperature is essential. © 2002 Biomedical Engineering Society. PAC2002: 8719Pp, 8754Br, 8719Uv, 8710+e     

Properties of the omega-hydroxylation system of docosahexaenoic or arachidonic acid in brain or liver homogenate of rat

The homogenate of a brain or liver obtained from a 1–55-day-old rat was incubated with NADPH and docosahexaenoic or arachidonic acid as the substrate. ω-Hydroxydocosahexaenoic or ω-hydroxyeicosatetraenoic acid from an incubation mixture of the homogenate was detected on a selected-ion monitoring chromatogram of reversed phase-HPLC-thermospray-mass spectrometry. ω-Hydroxylation activity in the brain homogenate considerably increased with growth up to 55 days. Activity in the liver homogenate decreased much with growth up to 55 days. ω-Hydroxylation activity in homogenates of rat brain gray matter, white matter, medula oblongata and cerebellum was much the same. ω-Hydroxylation activity of docosahexaenoic acid in rat brain homogenate was maximal at pH 7.5–8.0 in 50 mM Tris-HCL buffer and was inhibited by CO gas, metyrapone, ADP-Fe³⁺, heat treatment at 100°C for 5 min and without NADPH. Based on these results, it is suggested that ω-hydroxylation activity is associated with cytochrome P-450 without NADPH-ADP-Fe³⁺-dependent lipid peroxidation, and the ω-hydroxylation system may be a metabolic pathway of the fatty acids in adult rat brain or neonatal rat liver. Since ω-hydroxyeicosatetraenoic acid produces relaxation of artery, it is suggested that blood flow changes in rat brain or liver with growth are caused by ω-hydroxylation activity changes in these organs with growth.     

Hyperglycemic and Hyperosmolar Responses to Graded Hemorrhage

Changes of the arterial plasma osmolality and of the glucose concentration were followed during a 30 min period of graded hemorrhagic hypotension (80, 50, and 30 mmHg) in the cat. Bleeding evoked a significant plasma hyperosmolality at all three hypotension levels and the responses were quantitatively related to the degree of hypotension. An approximate steady state increase in the arterial plasma osmolality was reached about 20 min after the start of the bleeding and it then averaged 8, 20, and 25 mOsm/kg H₂O at 80, 50, and 30 mmHg, respectively. Bleeding also evoked an increase in the plasma glucose concentration, which almost entirely accounted for the observed hyperosmolality, especially at 80 and 50 mmHg. In late stages of hypotension at 30 mmHg, elevated plasma lactate and potassium concentrations contributed to the overall hyperosmolality. — Previous hemorrhagic hypotension experiments at 50 mmHg (Järhult 1975 b) have shown that hyperosmolality serves as an important regulator of the plasma and extracellular fluid volumes during bleeding. The present results indicate that such an osmolar compensatory mechanism is operating over wide ranges of hemorrhagic hypotension.