Electrical stimulation of the medial prefrontal cortex increases dopamine release in the striatum

Exogenous and endogenous glutamate has been shown to evoke dopamine (DA) release in the striatum using both in vitro and in vivo techniques. We hypothesized that stimulation of the prefrontal cortex (PFC) would phasically enhance striatal DA release via the glutamatergic corticostriatal pathway. To test this hypothesis, in vivo brain microdialysis was employed to measure extracellular concentrations of DA in the striatum during electrical stimulation of the PFC. Five rats were implanted with bilateral electrodes located in the medial PFC and dialysis probes in the dorsal striatum. Two days later the PFC of these awake, freely moving rats was stimulated first at 50 microA and then at 100 microA for 20 minutes at 2-hour intervals. Both currents significantly increased DA release. Extracellular DA rose rapidly during stimulation, peaked immediately afterward, and then slowly returned to baseline values. Dopamine reached 118% of baseline values with 50 microA stimulation and 138% with 100 microA stimulation. Histologic analysis using the fluorescent retrograde dye Fluoro Gold confirmed that cells projecting to the vicinity of the striatal dialysis probe originated in the vicinity of the PFC electrodes. These results provide direct evidence for phasic, excitatory modulation of striatal DA release by the PFC.     

The directional effects of passive eye movement on the directional visual responses of single units in the pigeon optic tectum

We have investigated the visual responses of 184 single units located in the superficial layers of the optic tectum (OT) of the decerebrate, paralysed pigeon. Visual responses were similar to those reported in non-decerebrate preparations; most units responded best to moving visual stimuli, 18% were directionally selective (they had a clear preference for a particular direction of visual stimulus movement), 76% were plane-selective (they responded to movement in either direction in a particular plane). However, we also found that a high proportion of units showed some sensitivity to the orientation of visual stimuli. We examined the effects of extraocular muscle (EOM) afferent signals, induced by passive eye movement (PEM), on the directional visual responses of units. Visual responses were most modified by particular directions of eye movement, although there was no unique relationship between the direction of visual stimulus movement to which an individual unit responded best and the direction of eye movement that caused the greatest modification of that visual response. The results show that EOM afferent signals, carrying information concerning the direction of eye movement, reach the superficial layers of the OT in the pigeon and there modify the visual responses of units in a manner that suggests some role for these signals in the processing of visual information.     

Mode of the autocrine/paracrine mechanism of growth hormone action

GH is synthesized at multiple extrapituitary sites suggestive of an autocrine/paracrine mechanism of action. We have investigated a possible autocrine/paracrine mechanism of GH action, compared the cellular response to exogenous versus endogenously produced GH, and determined the nature of the interaction between external stimuli and endogenously produced GH. BRL cells expressing the GH receptor were transiently transfected with expression plasmids containing either the hGH or the bGH gene and the response of the cell was measured by CAT reporter plasmids requiring either STATs 1 and 3 or STAT5 for their response. Transient transfection of the hGH gene resulted in hGH accumulation in the cell and secretion into the media. The functional response through STATs 1 and 3 and STAT5 obtained with endogenously produced hGH was comparable or greater in magnitude to that obtained with the maximal stimulatory dose of exogenous hGH. Similar results were obtained with an expression plasmid containing the bGH gene. Endogenously produced hGH interacted in an additive manner when combined with submaximal doses of both exogenous hGH and serum. Such results were also observed in a more physiologically relevant mammary carcinoma cell line (MCF-7). The nonreceptor-dimerizing hGH antagonist, hGH-G120R, used in cells expressing the homologous receptor extracellular domain was able to only partially inhibit the response of the cell to endogenously produced hGH, in contrast to full inhibition of exogenous hGH. We therefore conclude that GH can function in an autocrine/paracrine manner, additive in effect to external stimuli.     

Delayed delivery of surviving triplet after fetal reduction and spontaneous abortion

In multiple pregnancies, survival of remaining fetuses after premature death and delivery of one fetus is uncommon. We report a case of a triplet pregnancy that was reduced to twins at the 14th gestational week and then had preterm premature rupture of membranes and intrauterine fetal death of one twin at the 17th gestational week. To save the surviving fetus, delivery of the dead fetus and ligation of the umbilical cord at the cervical level were performed. We also performed McDonald cervical cerclage to keep the placenta of the dead fetus as well as that of the surviving one in the uterine cavity. After a series of aggressive procedures, including immediate administration of tocolytic agents, and antibiotic prophylaxis to prevent infection and preterm labor, the surviving fetus was delivered vaginally 73 days later due to intractable uterine contractions. After a 10-week hospital stay, the infant boy, weighing 2,500 g, was discharged without any sequelae. To our knowledge, this was the longest interval between deliveries in a triplet pregnancy reported in Taiwan. With adequate intensive management, a satisfactory outcome of the fetus and mother in such cases is possible.     

Prolongation and enhancement of postischemic c-fos expression after fasting

BACKGROUND AND PURPOSE: A rapid but transient expression of c-fos after cerebral ischemia has been extensively documented. However, the mechanism of this induction and whether induction of c-fos is neuroprotective or detrimental to the brain after ischemia is presently not clear. Fasting before transient cerebral ischemia has been shown to reduce delayed neuronal necrosis and infarct volume. The purpose of the present study was to examine the effect of preischemic fasting for 24 hours on the expression of c-fos after transient focal cerebral ischemia. METHODS: Focal cerebral ischemia was induced by temporary occlusion of the right middle cerebral artery and both common carotid arteries for 60 minutes. Male Long-Evans rats weighting 250 to 300 g were randomly divided into two groups: fed (control group) and food deprived for 24 hours (fasted group) before ischemic surgery. Infarct volumes were measured on the basis of triphenyltetrazolium chloride-delineated infarct areas, and plasma glucose levels were determined by the glucose oxidase method. Temporal and spatial expression of c-fos was assessed by Northern blot analysis, in situ hybridization, and immunohistochemistry. RESULTS: Fasting for 24 hours before 60 minutes of ischemia resulted in a 26.6% decrease in preischemic plasma glucose levels and a 74.5% reduction in infarct volumes in the fasted group compared with the control group. A rapid but transient induction of c-fos mRNA was observed in the ischemic cortex in control animals after 60 minutes of ischemia. Fasting not only prolonged but also enhanced the intensity of c-fos expression in the ischemic cortex. Regional c-fos expression was also different between these two groups. CONCLUSIONS: The results support the contention that c-fos expression may be compatible with its purported neuroprotective role in selected experimental paradigms. The signaling mechanisms underlying the effect of fasting and subsequent lowering of plasma glucose levels on postischemic c-fos expression remain to be explored.     

Prospective study of effect of switching from cigarettes to pipes or cigars on mortality from three smoking related diseases

OBJECTIVE: To estimate the extent to which cigarette smokers who switch to cigars or pipes alter their risk of dying of three-smoking related diseases-lung cancer, ischaemic heart disease, and chronic obstructive lung disease. DESIGN: A prospective study of 21520 men aged 35-64 years when recruited in 1975-82 with detailed history of smoking and measurement of carboxyhaemoglobin. MAIN OUTCOME MEASURES: Notification of deaths (to 1993) classified by cause. RESULTS: Pipe and cigar smokers who had switched from cigarettes over 20 years before entry to the study smoked less tobacco than cigarette smokers (8.1 g/day v 20 g/day), but they had the same consumption as pipe and cigar smokers who had never smoked cigarettes (8.1 g) and had higher carboxyhaemoglobin saturations (1.2% v 1.0%, P < 0.001), indicating that they inhaled tobacco smoke to a greater extent. They had a 51% higher risk of dying of the three smoking related diseases than pipe or cigar smokers who had never smoked cigarettes (relative risk 1.51; 95% confidence interval 0.96 to 2.38), a 68% higher risk than lifelong non-smokers (1.68; 1.16 to 2.45), a 57% higher risk than former cigarette smokers who gave up smoking over 20 years before entry (1.57; 1.04 to 2.38), and a 46% lower risk than continuing cigarette smokers (0.54; 0.38 to 0.77). CONCLUSION: Cigarette smokers who have difficulty in giving up smoking altogether are better off changing to cigars or pipes than continuing to smoke cigarettes. Much of the effect is due to the reduction in the quantity of tobacco smoked, and some is due to inhaling less. Men who switch do not, however, achieve the lower risk of pipe and cigar smokers who have never smoked cigarettes. All pipe and cigar smokers have a greater risk of lung cancer than lifelong non-smokers or former smokers.