Stimulation of nerve growth factor and substance P expression in the iris–trigeminal axis of diabetic rats—involvement of oxidative stress and effects of aldose reductase inhibition

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P<0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P<0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NGF, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes—a mechanism that might participate in iritis.     

Neuropathology in non-human immunodeficiency virus-infected drug addicts: hypoxic brain damage after chronic intravenous drug abuse

Neuropathological studies were carried out on 180 human immunodeficiency virus-seronegative intravenous drug addicts. The findings in victims of acute heroin intoxication (n = 116) were congestion (99.1%), capillary engorgement (68.1%), and/or perivascular bleeding (68.1%) – hemodynamic processes attributable to toxic primary respiratory failure. In a high percentage of these cases (88%), cerebral edema was also present. In 18 cases of acute heroin intoxication who survived for periods of hours or days, the sole postmortem finding was ischemic nerve cell damage, resembling that typically seen in systemic hypoxia. Semiquantitative analysis revealed nerve cell loss in the hippocampal formation and/ or Purkinje cell layer in 26% of the 162 chronic drug abusers. By contrast, in nearly 80% of these cases, the hippocampus showed enhanced expression of glial fibrillary acid protein by astrocytes and/or a proliferation of microglia, demonstrated by CD68 expression. Since such reactive processes are produced by primary neuronal damage, it can be assumed that chronic intravenous drug abuse results in obviously ischemic nerve cell loss. This could be demonstrated in the hippocampus, but it must also occur throughout the whole brain. The demonstration of ischemic nerve cell damage and neuronal loss or secondary reactive alterations has not been described previously. Received: 31 March 1995 / Revised, accepted: 27 November 1995     

NGF prevents the changes induced by monocular deprivation during the critical period in rats

Photic evoked responses were recorded from the striate cortex of Long-Evans hooded intact, monocular visual deprivation (MD) and MD treated with NGF rats. The averaged visual evoked responses (AVER) were obtained from both hemispheres and provided comparison after binocular photic stimuli between the contralateral and the ipsilateral striate cortex with relation to the MD eye. One month of monocular visual deprivation at the critical period of development resulted in marked reduction of the amplitudes of AVER components as compared to the control recordings (P < 0.001). These changes of the AVER could be prevented by NGF infusion to lateral ventricle at the dosage of 2.0–2.4 μg/day for four weeks during the monocular deprivation. In conclusion, the change of AVER amplitudes induced by monocular visual deprivation during the critical period of development can be prevented by NGF infusion to lateral ventricle.     

Effects of trapidil-derivatives on calcium channel currents in isolated ventricular cells from mice

Summary A single glass micropipette voltage clamp technique with intracellular dialysis was used to study the effects of the trapidil derivatives AR 12–456 and AR 12–463 on Ca channel currents carried by Bat+ in isolated ventricular cells from mice hearts. Inspite of a more potent inhibition of the cAMP phosphodiesterase from heart (Bartel et al. 1985) a reversible Ca channel blocking action of both compounds could be observed. The concentration of half maximal block was calculated to about 50 mol/l for both derivatives tested. Neither a shift in the current-voltage relationships nor a significant change in the potential for half maximal activation was found. The maximal Ba²⁺ -conductance was reduced. The steady state inactivation was shifted towards more negative potentials by application of 100 mol/l AR 12–463. The decay of the Ba currents was accelerated in the range of the applied test potentials between –20 and +20 mV. It is concluded that the new trapidil derivatives with more potent inhibitory action on cardiac phosphodiesterase than trapidil can block myocardial Ca channels. Send offprint requests to B. Nilius     

Computerized axial tomo-epidurographic and radiographic documentation of unilateral epidural analgesia

A 23-year-old primigravid patient who received epidural analgesia for pain of labour presented with persistent, apparently irremediable, unilateral analgesia. Computerized axial tomo-epidurography demonstrated absence of circumferential spread due to lateral placement of the catheter. Transforaminal escape of contrast medium into the paravertebral area had occurred and anterior and posterior midline partitioning of the epidural space was obvious. All the usual measures to promote contralateral analgesia, except re-insertion of the catheter, had been tried without success.     

Local blood flow and metabolism of the tongue before and during panting in the dog

Summary The effects of hyperthermia on blood flow and oxygen consumption of the tongue were investigated in anesthetized dogs. For comparison, blood flow through the skin and deep muscle of the hind leg was also measured in some animals. Increasing blood temperature revealed a biphasic response of lingual blood flow. At 41°C blood temperature respiratory frequency was twice that of control and there was a reduction of lingual blood flow, while resistance of the lingual bed was increased significantly. The arterio-venous oxygen difference (AVDO₂) of lingual blood was markedly increased at this level and the of the tongue was like-wise significantly greater than control. At 41.9°C, the steep increase of respiratory frequency was accompanied by a marked fall in lingual resistance as evidenced by a four-fold increase of lingual blood flow. The systemic AVDO₂ rose at this temperature, while the lingual AVDO₂ fell dramatically. There was no further increase of lingual . At both temperature levels the blood flow through the skin did not change substantially, while the deep muscle blood flow slightly increased. The mean arterial pressure showed a progressive fall during hyperthermia. It is assumed that the decrease of lingual blood flow at elevated blood temperature without panting is due to a redistribution of cardiac output to areas other than the tongue. The increase of lingual blood flow without an additional increase of lingual during panting may be explained solely as a mechanism for heat dissipation. The fact that the decrease of lingual resistance was demonstrated in immobilized animals concomitant with high frequency phrenic burst activity suggests that the decrease of lingual resistance and panting may be induced by a common central integrating mechanism.