Electrodermal activity in nonmedicated hyperthyroid patients having no depressive symptoms.

The aim of the present study was to investigate whether the alteration in hypothalamic-pituitary-thyroid axis function results in electrodermal abnormality without causing marked psychiatric manifestations or not. Electrodermal activity was recorded with the skin conductance unit and IBM-AT computer. Basal levels of electrodermal activity (EDA), as well as responsivity to repeated insignificant acoustic stimulation were studied in 24 nonmedicated hyperthyroid patients and 35 healthy controls. The outcome of psychiatric rating scores indicated that patients had low anxiety scores and normal depression scores. The basal levels of thyroid hormones were higher in patients, when compared with the control group. On the analysis of EDA, we found lower onset latency and duration of the skin conductance response and higher skin conductance level in nonmedicated patients than healthy controls. The results above provide supporting evidence that the change of hypothalamic-pituitary-thyroid axis function results in abnormal EDA, without causing marked psychiatric manifestations.

Utility of P300 auditory event related potential latency in detecting cognitive dysfunction in growth hormone (GH) deficient patients with Sheehan's syndrome and effects of GH replacement therapy.

OBJECTIVE: Impaired cognitive function has been demonstrated in adults with growth hormone (GH) deficiency (GHD) by using different neuropsychological tests. Despite several studies, present knowledge about the impact of GHD and GH replacement therapy (GHRT) on cognitive function is limited. P300 event-related potential (ERP) application is a well-established neurophysiological approach in the assessment of cognitive functions including the updating of working memory content and the speed of stimulus evaluation. GHD is a well-known feature of Sheehan's syndrome and cognitive changes due to GHD and the effects of GHRT remain to be clarified. The present study was designed to investigate the effects of GHD and 6 months of GHRT on cognitive function in patients with Sheehan's syndrome by using P300 latency. DESIGN AND METHODS: The study comprised 14 patients with Sheehan's syndrome (mean age, 49.5+/-7.8 years) and 10 age-, education- and sex-matched healthy controls. With hormone replacement therapy, basal hormone levels other than GH were stable before enrollment and throughout the GHRT. The diagnosis of GH deficiency was established by insulin-tolerance test (ITT), and mean peak level of GH in response to insulin hypoglycemia was 0.77+/-0.35 mIU/l. Treatment with GH was started at a dose of 0.45 IU (0.15 mg)/day in month 1, was increased to 0.9 IU (0.30 mg)/day in month 2 and was maintained at 2 IU (0.66 mg)/day. Initially baseline auditory ERPs in patients and controls were recorded at frontal (Fz), central (Cz), and parietal (P3 and P4) electrode sites. In the patient group, ERPs were re-evaluated after 6 months of GH replacement therapy. During each session P300 amplitude and latency were measured. RESULTS: Mean serum insulin-like growth factor-I (IGF-I) concentration in the patient group before GHRT was 23+/-13 ng/ml. After 6 months of GH therapy mean IGF-I significantly increased to an acceptable level, 234+/-71 ng/ml (P<0.05). The mean latencies (at all electrode sites) of the patients before GHRT were found to be significantly prolonged when compared with those of normal controls (P<0.05). After 6 months of GHRT mean P300 latencies (at all electrode sites) were decreased significantly when compared with latencies before treatment (P<0.05). CONCLUSIONS: The present study, using P300 ERP latencies, therefore suggests an impairment of cognitive abilities due to severe GHD in patients with Sheehan's syndrome and an improvement of cognitive function after 6 months of physiological GHRT. Moreover, this was a novel application of P300 ERP latencies in cognitive function detection in patients with GHD. Further studies with different patient groups need to be done to assess the clinical use of this electrophysiological method in the diagnosis of cognitive dysfunction due to GHD.

Electrodermal activity in hypothyroid patients and healthy subjects.

The involvement of the central nervous system either in hypothyroidism or in hyperthyroidim has previously been shown on the basis of visual, auditory, somatosensory, and central motor evoked potential studies by some investigators. In to our previous study, we found that abnormal electrodermal activity in nonmedicated hyperthyroid patients was not associated with psychiatric symptoms. In this study, our purpose was to investigate whether hypothyroidism results in electrodermal abnormalities in the absence of measurable psychiatric symptoms. Electrodermal activity was recorded with a skin conductance unit connected to a personal computer. Basal levels of electrodermal activity and responsiveness to repeated acoustic stimulation were studied in 14 nonmedicated hypothyroid patients and 14 healthy controls. Psychiatric rating scores indicated that patients and healthy controls had normal levels of anxiety and depression. Hypothyroid patients had lower skin conductance levels, lower fluctation rates and prolonged onset latencies compared with controls. None of the hypothyroid patients had amplitude changes. In conclusion, hypothyroid patients may have abnormal electrodermal activity that is related to the change of hypothalamic-pituitary-thyroid axis function, without associated psychiatric symptoms.

The relation between skin conductance level and plus-maze behavior in male mice.

The present study examined the correlation between anxiety scores and skin conductance level in 29 male Swiss Albino mice. Skin conductance (SC) was recorded with the SC unit and IBM-AT computer. Anxiety scores of mice were obtained from the elevated plus-maze test. The main result of the present study indicates that SC levels (SCLs) are negatively correlated with plus-maze behavior scores (both entries and time spent on the open arms). Our results are consistent with the findings which suggests that the higher the anxiety level the higher the SCL. This study further demonstrates the utility of SCL as a measurement for identifying anxiety in mouse. The interrelation between SCLs and plus-maze scores and possible explanations of the results are discussed.

Contraceptive steroids increase erythrocyte lipid peroxidation in female rats.

In order to investigate the effects of contraceptive steroid combinations on lipid peroxidation in the erythrocyte membranes, adult female rats were divided into 2 groups for short- and long-term investigations; each group was then subdivided into 5 subgroups according to orally given low and high doses of EE/NEA (ethinyl estradiol/norethisterone acetate) and EE/LNG (ethinyl estradiol/levonorgestrel) combinations and control group. Since EE was included in each combination, the groups were named according to the progestin (NEA, LNG) components. At the end of the experiment periods, lipid peroxidation in the erythrocyte membranes from rats was measured. When compared to the controls, except low-dose LNG groups, lipid peroxidation levels were increased in all study groups. It was seen that the effect of NEA and LNG combinations on lipid peroxidation was not time-, but dose-dependent. When these combinations were compared to each other, different effects of NEA and LNG on lipid peroxidation were not detected in the experiment period. As a result, the increased lipid peroxidation following the administration of contraceptive steroid combinations is a very important finding that should be taken into account, in addition to the effects of these steroids on lipid and lipoprotein metabolism.

Effects of grayanotoxin-I on threshold intensity and compound action potential of frog sciatic nerve.

Effects of (Grayanotoxin-I) GTX-I, one of the second group of sodium channel toxins, have been investigated on threshold stimulus voltage and upstroke velocity of isolated frog sciatic nerve. GTX-I was isolated from toxic honey obtained from the Black Sea Region of Turkey, and used in the experiments at the concentrations of 3.50(-5), 3.10(-4), 3.10(-3) M. The threshold stimulus voltage and upstroke velocity of CAP were decreased and conduction velocity of frog sciatic nerve preparations was increased by GTX-I. The effects were dose-dependent. As a results, it is suggested that the decrease of threshold stimulus voltage and upstroke velocity of CAP and the increase of conduction velocity of frog sciatic nerve is mainly due to an increase in resting membrane permeability to sodium ions.

Gamma response of the brain: a multifunctional oscillation that represents bottom-up with top-down processing.

This paper deals with the functional correlates of the gamma response of the brain. A critical review of the literature findings reveals the existence of two types of gamma responses: an early gamma that fulfills sensory functions and a late gamma that fulfills perceptual-cognitive functions. However, even the early gamma shows individual differences. Such a finding points to the existence of top-down influences on sensory processes and to a parallel-processing model for brain function.

Effect of acute starvation on rat diaphragm function.

The effects of 130 h of acute starvation on diaphragm contractility fatigue were studied in isolated rat diaphragm strip preparations with phrenic nerve stimulation. Compared with controls, starvation produced a reduction in body and diaphragm weights. Twitch and tetanic tensions were reduced by starvation; however, when the force was calculated as the strength (normalized for the weight or muscle cross-section area of the diaphragm), no difference was observed between the control and experimental groups. Starvation induced a significant downward shift in the force-frequency relationship, and also increased diaphragm fatigability, but it had no effect on twitch contraction and relaxation time. We conclude that 130 h of acute starvation decreases diaphragmatic force and endurance, but the strength does not change, because of the reducing diaphragmatic mass.

Zinc-induced alterations in contractile properties of rat diaphragm muscle in vitro.

The effect of zinc ions on the isometric contraction of rat diaphragm muscles in the presence and in the absence of external calcium was studied. Using a transducer, the isometric force was measured as a function of supramaximal electrical stimulation, either directly or indirectly applied to the muscle. The following parameters were measured: peak twitch tension, PT, twitch contraction time, CT, relaxation half-time, RT-1/2, and peak rates of tension increase and decrease, +dP/dt and -dP/dt. The following zinc-induced alterations were observed: an increase of the PT; a decrease of the RT-1/2; an increase in the +dP/dt and -dP/dt. The CT was not changed significantly. Our results suggest that zinc ions have a positive inotropic effect on isolated diaphragm muscle. The increase in PT may be explained by a zinc-activated Ca2+ uptake by sarcoplasmic reticulum. This was followed by an increase in the rate of rise of tension development, which was secondary to increased -dP/dt. The mechanism(s) by which extracellular Ca2+ contributes to this action of zinc is not known.

Dependence of fatigue properties on the pattern of stimulation in the rat diaphragm muscle.

Diaphragm fatigue was studied in isolated phrenic nerve diaphragm strips from 28 Swiss Albino rats. Three procedures were used to estimate the isometric twitch characters and force frequency responses to fatigue of the rat diaphragm at different rates of phrenic nerve stimulation. Diaphragm fatigue was induced by using low frequency stimulation (0.2 ms pulse duration, at 5 Hz frequency, 3 min), high frequency stimulation (0.2 ms pulse duration, at 50 Hz frequency, 3 min), and by production brief submaximal contraction (25 Hz, for 160 ms at the rate of 1/s for 45 contractions). Tension was reduced to 26.67 +/- 5.10% and 6.59 +/- 2.64% and 68.69 +/- 2.45% of the initial value at the end of the low and high frequency and brief submaximal stimulation, respectively. In all the fatigue experiments, twitch tension and tetanic tension decreased, contraction and 1/2 relaxation time prolonged and force-frequency curves shifted to the right. The most significant changes were observed in low frequency fatigue whereas the most moderate ones were recorded in brief submaximal fatigue. It was concluded that fatigue in the rat diaphragm depended on the frequency and duration of stimulation as well as on the number of stimuli delivered to the muscle. Various mechanisms of muscle fatigue are described in the discussion to explain the observations made in the present investigation.

ELECTRODERMAL RESPONDING IN HYPERTHYROID PATIENTS.

The effects of hyperthyroidism on electrodermal habituation and responsiveness were examined in 43 hyperthyroid patients who were divided in two groups (medicated and unmedicated). In a comparison of 43 hyperthyroid and 43 normal controls; among patients with hyperthyroidism a great number of nonresponders were found. The distributions of SCR in habituation series in both group were almost the same but hyperthyroid patients were in slower habituation status than controls. These findings suggest that electrodermal nonresponsiveness or slow habituation in hyperthyroid patients might be considered as a function due to changes in the metabolism of biogenic mines in the central nervous system.

Effect of reversed light-dark cycle on skin conductance in male rats.

Reversal of light-dark cycle was used to investigate the effect of the circadian changes on skin conductance, a tonic electrodermal activity parameter, in rats. Rats were adapted for 3 wk. to one of two lighting programs. The animals on the normal cycle were illuminated from 08.00-20.00; on the reverse cycle, from 20.00-08.00. Although during Week 1 to Week 3, skin conductance increased gradually in both groups, this increase was more dramatic in rats adapted to light from 20.00 to 08.00 than in the other group. When the animals on the reverse cycle were readjusted to a normal circadian cycle for 3 weeks, skin conductance decreased gradually to initial values. At Weeks 1, 2, 3, and 6, skin conductance was significantly higher in rats on the reverse light-dark cycle than in those on the normal cycle. The present data suggest that changes in normal light-dark conditions affect skin conductance in rats.

The effect of contraceptive steroids on plasma lipoprotein metabolism in female rats (II).

In order to investigate the effects of two contraceptive steroids given orally, which contain ethinyl estradiol in combination with different types and doses of progestins, on plasma lipoprotein metabolism, rat groups named according to progestin components were designated as short-and long-term groups of norethisterone acetate and levonorgestrel at low-and high-doses. At the end of the experiments, plasma triglyceride, phospholipid, apolipoprotein A1 and B, LDL-, HDL-, HDL2- and HDL3-cholesterol levels and hepatic lipase activity were measured. When compared to controls, phospholipid and LDL-cholesterol were increased in all groups; triglyceride levels were also increased in all short-term groups, but only in low-dose norethisterone and high-dose levonorgestrel of long-term groups. HDL- and HDL3- cholesterol were decreased in all groups, except in low-dose levonorgestrel groups, but HDL2-cholesterol were lower only at high doses and long period. In short-term, an increase in apolipoprotein A1 levels was significantly important at high doses; in long-term apolipoprotein A1 was increased at low doses, while decreased at high doses. Apolipoprotein B was elevated only in long-term high dose of norethisterone acetate group. Hepatic lipase activity was increased in long-term high-dose of levonorgestrel group, whereas decreased in all other groups. In conclusion, the data presented was interpreted that the effects of these combinations used in the study on plasma lipoprotein metabolism may be related to the changes observed in hepatic lipase activity.

The effect of contraceptive steroids on hepatic cholesterol metabolism in female rats (I).

In order to determine effects of contraceptive steroids with respect to dose, progestin type and duration of administration, on hepatic cholesterol metabolism, rats were treated with two different (ethinyl estradiol/norethisterone acetate and ethinyl estradiol/levonorgestrel) combinations orally at two different-low and high-doses and- short and long-terms. At the end of the experiments, total cholesterol and acetoacetate levels in plasma samples and HMG-CoA synthase and AcAc-CoA thiolase activities in the livers of rats were measured. In all groups, acetoacetate was found to be higher than in controls, and except in low dose- ethinyl estradiol/levonorgestrel treated groups, total cholesterol was also increased. In the short period treatments HMG-CoA synthase and AcAc-CoA thiolase (except in low dose-ethinyl estradiol/levonorgestrel group) activities were increased. But enzyme activities were either decreased or not changed in long period treatments. It is suggested that increased enzyme activities in short period treatments may increase total cholesterol levels, and that in time, these levels may lead to a suppression of enzyme activities.

Effects of honey containing grayanotoxin I on frog gastrocnemius muscle.

The presence of grayanotoxins (GTX-I, GTX-II and GTX-III) in honey samples from the Mediterranean Sea and Black Sea regions of Turkey and the effect of honey containing GTX-I on the threshold stimulus voltage of frog gastrocnemius muscle were studied. We used 2 groups of gastrocnemius muscles isolated from curarized or noncurarized frogs. The threshold voltage was measured by external perfusion with a polygraphic system. Isolated muscle preparations were perfused separately with Clark-frog-Ringer's solution containing honey solutions from the Mediterranean Sea region (normal) or with honey solutions from the Black Sea region (GTX-I-containing, poisonous). There was no significant difference between the normal and poisonous honey groups data with the curarized preparations. But in the noncurarized preparations, the honey containing GTX-I significantly decreased the threshold voltage in comparison with normal honey. These findings suggest the effect of GTX-I on frog neuromuscular junctions is due to an increase in membrane permeability to sodium ions.

The effects of theophylline and caffeine on the isolated rat diaphragm.

It is a well known fact that theophylline enhances the force of diaphragmatic contraction and delays fatigue. The action of caffeine which is a methylxanthine analogue on skeletal muscle are complex. It was claimed in few studies that the caffeine was more effective on the diaphragmatic contractility than the theophylline. The aim of this study is to compare the effects of theophylline and caffeine on the tension generated by fresh and fatigued diaphragmatic muscle. Studies were performed in vitro on diaphragmatic muscle strips of rats activated by electrical stimuli applied via the phrenic nerve. Isometric twitch characteristics (twitch tension, contraction and 1/2 relaxation time) were measured. Force-frequency responses were generated using twitches and tetanic contractions produced by stimulating the phrenic nerve with 0.2 ms pulses at 10, 20, 50 and 100 Hz for 1 s with 30 s intervals. Moderate fatigue was then induced by repeated submaximal contractions (25 Hz, 160 ms, at the rate of 1/s for 45 contractions). In fresh muscle 1 mM theophylline and 1 mM caffeine increased diaphragmatic tension 40.98 +/- 8.50% and 82.30 +/- 12.21% of the initial value respectively. Theophylline did not alter contraction time but prolonged 1/2 relaxation time, whereas caffeine had no effect on any one. Theophylline induced force production in all frequencies. Caffeine caused an increase in force only in < 20 Hz, but a decrease in 50 and 100 Hz. In brief submaximal fatigue, both 1 mM theophylline and 1 mM caffeine partly prevented fatigue (effect of caffeine was more potent). This study suggests that caffeine has a greater effect than theophylline on the muscle. Possible mechanism(s) of action of theophylline and caffeine on diaphragmatic contractility and fatigue were discussed. It may well be the fact that they might have different mechanisms of action on the isolated rat diaphragm.

Rat diaphragm muscle contraction with and without oxygen enrichment.

We investigated the effect of deprivation of oxygen circulation in the organ bath on the tension generation of the diaphragm in vitro. Adult male Swiss Albino rats were quickly killed and the left hemidiaphragms removed. Isolated phrenic nerve-diaphragmatic strip preparations were placed in an individual organ chamber containing Krebs solution and were connected to a force displacement transducer. The solution was maintained at 32 degrees C and bubbled with 95% O2-5% CO2. For the measurement of isometric twitch characteristics, supramaximal voltage was delivered via phrenic nerve electrodes. After turning off the gas circulation, isometric twitch characteristics were determined at 5, 10, 15, and 20 minutes. Then the muscle was allowed to recover under aerobic conditions (i.e., while bathed in a fresh solution, gassed with 95% O2-5% CO2). The isometric contractile properties were determined at the same intervals. In spite of no change in contraction time (CT) and relaxation time (1/2 RT), twitch amplitude (Pt) decreased following the termination of oxygen circulation (p < 0.05). The twitch tension improved in the recovery period but the decrease of tension developed more rapidly than the increase of tension development. We suggest that the decrease in the twitch tension was possibly due to a direct effect of intracellular acidosis. This study shows that no important change occurred in Ca+2 release and/or in the uptake in the sarcoplasmic reticulum, because of the finding of the CT and 1/2 RT values.

Changes in serum protein lipid and electrolyte levels in rabbits at mid-altitude.

1. The effects of mid-altitude on the profiles of total serum lipid, cholesterol, fibrinogen, albumin, Ca2+, Cl-, Na+ and K+ were investigated in rabbits for 22 days. From 30 rabbits living at sea level 15 were exposed to 1170 m and 15 to 2240 m altitude. 2. When compared with sea level values; total protein, albumin and K+ significantly decreased up to 5th day (P less than 0.01), then they gradually increased. 3. Total lipid, cholesterol, Ca2+, Cl- and Na+ levels elevated in 2nd day (P less than 0.01) then they gradually decreased to their sea-level values. 4. It was concluded that the adaptation mechanisms begin at mid-altitudes.

Peritoneal mesothelioma and malignant lymphoma in mice caused by fibrous zeolite.

Dust from the village of Karain containing the fibrous zeolite erionite, talc, and physiological saline were tested by intraperitoneal injection in 486 Swiss albino mice. Malignant tumours were found in 84 (41 mesotheliomas, 31 lymphomas, 1 peripheral epidermoid carcinoma, and 11 lymphomas and mesotheliomas together) of the 321 animals which died spontaneously within nine to 32 months after injection of Karain dust (26.1%). Three mesotheliomas and no lymphomas were found among 24 animals injected in the same way with talc during the same time (12.5%). In 46 control animals injected with physiological saline three mesotheliomas and one lymphoma were seen (8.7%). Thus Karain dust appears to be a potent carcinogen, causing both mesotheliomas and malignant lymphomas.

Immunoglobulin-G and creatinine levels in rabbits in altitude adaptation.

The changes of immunoglobulin-G and creatinine levels in mid-altitude were investigated in rabbits. The animals living at sea level were exposed to 2240 m altitude for 22 days period. When compared with sea level values; immunoglobulin-G levels were significantly low. Serum creatinine level decreased significantly in the 2nd day, then reached the sea level amount on the 12th day. On the 22nd day a significant increase was observed. It was concluded that the decrease in immunoglobulin-G values may be due to the depression of protein synthesis. The increase in plasma creatinine level would be explained by the decrease in urine.