Striatal dopaminergic abnormalities in human cocaine users

OBJECTIVE: Previous human postmortem experiments have shown an abnormally high number of dopamine uptake sites in the striatum of chronic cocaine users, which might contribute to cocaine withdrawal symptoms such as depression and suicidality. Previous inconsistencies in results were perhaps related to selective radioligand affinity changes or a coexisting loss of dopamine neurons. METHOD: In the present study, binding of the cocaine analog [3H]WIN 35428 to the dopamine transporter was assayed in postmortem striatal samples from 15 cocaine-using subjects and 15 matched comparison subjects to determine whether there were differences in number of binding sites or in affinity. Binding to the vesicular monoamine transporter, a measure of total dopaminergic terminals, was also assessed by using the radioligand (+)-[3H]dihydrotetrabenazine (DTBZ). RESULTS: Striatal [3H]WIN 35428 binding sites were significantly more numerous in the cocaine users: the mean Bmax value was 9.0 fmol bound/microg protein (SD = 2.8) for the cocaine users but only 6.0 (SD = 1.7) for the comparison subjects. Severity of chronic cocaine use was significantly related to [3H]WIN 35428 binding level. [3H]DTBZ binding was significantly lower in the cocaine users (mean = 330 nCi/mg, SD = 42) than in the comparison subjects (mean = 374, SD = 68). CONCLUSIONS: The present results confirm that cocaine users have a high number of dopamine transporter binding sites on dopaminergic neurons, despite an apparent low number of total dopamine terminals. These abnormalities may contribute to the abnormalities in subjective experience and behavior characteristic of chronic cocaine abusers.     

Striatal neuropeptide Y neurones are not a target for thalamic afferent fibres

This study examined at the ultrastructural level the putative relationships between afferent fibres coming from the parafascicular nucleus of the thalamus and neuropeptide Y (NPY)-containing neurones in the rat striatum. Experiments used a combination of anterograde transport of the biotin dextran amine to label the thalamo-striatal pathway and immunogold labelling to reveal the NPY-containing neurones at the electron microscopic level. Examination of sections from three animals failed to demonstrate thalamic terminals in synaptic contact with NPY-immunoreactive dendrites or cell bodies, although both types of labelled elements were frequently involved in synaptic complex with unlabelled profiles. These results strongly suggest that striatal NPY interneurones are not under the direct influence of the main component of the thalamo-striatal system.     

Proteases and their inhibitors are indicative in gestational disease

OBJECTIVE: To assess whether various proteolytic factors which are involved in trophoblast invasion show different concentrations in plasma and placenta of patients with HELLP syndrome, pre-/eclampsia and highly pathological Doppler flow measurements but without additional complications (hpD). DESIGN: Case control and observational study; 18 women with HELLP syndrome, 21 with pre-/eclampsia, 13 with hpD, as well as healthy pregnant women (matched pairs); statistical analysis: sign test and Wilcoxon test. RESULTS: Urokinase-type plasminogen activator (uPA), uPA receptor, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1), matrix metalloproteinases MMP-8, MMP-9 and tissue inhibitor of metalloproteinases TIMP-1 were measured by ELISA. PAI-1 plasma levels are significantly elevated in all three groups studied. In HELLP syndrome, tPA and TIMP-1 are also elevated, and in patients with hpD, MMP-8 is increased, whereas MMP-9, and TIMP-1 are lower. In placenta extract, only pre-/eclampsia shows reduced MMP-9 concentrations. CONCLUSIONS: The increased frequency of small-for-gestational-age infants observed in all three study groups is an expression of impaired placental implantation and remodelling processes. These disturbances manifest themselves in the form of changes in some of the factors in plasma and placenta extract that are involved in these processes.     

Serum testosterone levels are not elevated in patients with ankylosing spondylitis

OBJECTIVE: Studies in patients with ankylosing spondylitis (AS) describe slightly elevated serum testosterone levels, but these studies were not properly controlled for possible confounders. METHODS: In a case-control study serum levels of sex steroids, luteinizing hormone, and sex hormone binding globulin (SHGB) were measured in patients with AS and in age and sex matched controls. The body mass index, smoking status, use of alcohol, and fat intake were recorded. RESULTS: Testosterone levels measured in serum extracts did not differ in 50 male patients with AS compared to controls (mean +/- SD 16 +/- 4 vs 15 +/- 5 nmol/l, respectively; p = 0.54). In unextracted serum, however, male patients showed elevated testosterone (p < 0.001) and dehydroepiandrosterone sulfate levels (p = 0.003), even after controlling for confounders (p < 0.001). One of 10 female patients had an elevated testosterone level in unextracted serum. The 17 male users and one of the 2 female users of phenylbutazone had the highest testosterone levels in unextracted serum, and all showed a significant decline after extraction. Serum levels of other sex steroids, luteinizing hormone, and SHGB did not differ significantly between patients and controls. CONCLUSION: Serum testosterone levels are not elevated in male patients with AS. Spuriously elevated testosterone levels in unextracted serum might be related to the use of phenylbutazone in our patient sample.     

Decreased immunoreactive androgen receptor levels are not the cause of isolated hypospadias

OBJECTIVE: To elucidate whether diminished levels of androgen receptor (AR) are the underlying cause for the development of hypospadias by determining AR levels in the foreskins of boys with hypospadias. PATIENTS AND METHODS: The content of AR was determined by a sensitive immunoblotting technique in extracts from preputial tissue obtained from 15 patients (mean age 2.5, SD +/- 1.5 years) with hypospadias and from seven controls (mean age 2.5, SD +/- 1.5 years). Immunoreactivity of the protein was measured by densitometry. RESULTS: No significant difference in mean AR content was found between those boys with hypospadias (2.1 +/- 0.9 fmol/mg protein, +/- SD) and the age-matched control group (2.2 +/- 0.3 fmol/mg protein). Stratification by the severity of hypospadias (distal and proximal on the shaft, and penoscrotal hypospadias) showed that the severity was not related to tissue AR levels. CONCLUSION: It is unlikely that hypospadias is caused by a decreased expression of AR.     

Striatal dopaminergic D1 and D2 receptors after intracerebroventricular application of alloxan and streptozocin in rat

The purpose of this study was to evaluate the changes in condylar position following bilateral sagittal split ramus osteotomy with 5- and 10-mm setback in 1 symmetric human cadaver mandibles. A Plexiglas device was constructed to determine the mandibular morphology and the movements of the condyle and the proximal segments before and after surgery. There was no statistically significant relationship between mandibular morphology or the magnitude of setback and changes in condylar position postsurgery. All condyles and rami tipped in a highly variable fashion in the coronal plane. In the axial plane, the lateral pole of the condyles rotated predominantly anteriorly; the left side rotated significantly more than did the right. In the sample studied, the position of the condylar and proximal segments was altered in a highly variable and unpredictable manner, regardless of the magnitude of setback or the morphology of the mandible.     

High dose levels are not necessary in rodent studies to detect human carcinogens

Guidelines for the conduct of rodent carcinogenicity studies stipulate that when the test substance is administered via the diet, its concentration need not exceed 5% of the diet. Since it is now apparent that human carcinogens are amongst the most potent of rodent carcinogens, it should be possible to detect accurately potential human carcinogens by using only relatively low dose levels in rodent studies. Our analysis of the potency of human carcinogens in rodent studies leads to the conclusion that, even after applying a safety factor of 10, there is no purpose in using dose levels higher than 500 mg/kg body weight or 1% in the diet.     

Long latency postural reflexes are under supraspinal dopaminergic control

Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior muscles induced by "toe-up" rotational perturbations is abnormal in standing patients with Parkinson's disease. To investigate the contribution of dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic neuroleptic medication (7 with mild parkinsonism), 8 patients with young-onset Parkinson's disease, and 4 patients with MPTP-induced parkinsonism. Results were compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial (predictable) perturbations of 4 degrees amplitude, (b) 10 serial (predictable) perturbations of 10 degrees amplitude, and (c) 20 randomly mixed (unpredictable) perturbations of either 4 or 10 degrees amplitude. In normal subjects, LL reflex amplitudes were adapted to match predictable variations in stimulus size, whereas under unpredictable conditions a "default" response emerged that anticipated the 10 degrees perturbation. LL reflex scaling under predictable conditions was intact in patients with neuroleptic-induced parkinsonism and young-onset Parkinson's disease, but the large default LL response under unpredictable conditions was absent. In patients with MPTP-induced parkinsonism, LL reflex scaling was absent during both predictable and unpredictable conditions. We conclude that abnormal scaling of posturally stabilizing LL reflexes is related to decreased supraspinal dopaminergic influence.     

Striatal dopamine dynamics are altered following an intranigral infusion of iron in adult rats

Exercise has a noted effect on skin blood flow and temperature. We aimed to characterize the normal skin temperature response to exercise by thermographic imaging. A study was conducted on ten healthy and active subjects (age=25.8+/-0.7 years) who were exposed to graded exercise for determination of maximal oxygen consumption (VO2 max), and subsequently to constant loads corresponding to 50%, 70%, and 90% of VO2 max. The skin temperature response during 20 min of constant load exercise is characterized by an initial descending limb, an ascending limb and a quasi-steady-state period. For 50% VO2 max, the temperature decrease rate was - 0.0075+/-0.001 degrees C/s during a time interval of 390+/-47 s and the temperature increase rate was 0.0055+/-0.0031 degrees C/s during a time interval of 484+/-99 s. The level of load did not influence the temperature decrease and increase rates. In contrast, during graded load exercise, a continuous temperature decrease of -0.0049+/-0.0032 degrees C/s was observed throughout the test. In summary, the thermographic skin response to exercise is characterized by a specific pattern which reflects the dynamic balance between hemodynamic and thermoregulatory processes.     

High blood cadmium levels are not associated with consumption of traditional food among the Inuit of Nunavik

The most reliable stereotactic methods in primates resort to ventricular as opposed to bony landmarks. The usual CA-CP system did not appear satisfactory for stereotaxy of the amygdala and anterior hippocampus. Variation studies on ventriculograms and reconstructions from histological material were done to find more reliable systems. The most precise system of coordinates for cartography and stereotaxy of the amygdala is based on the 'amygdalar notch', a ventricular diverticulum forming the angle between the inferior and anterior borders of the temporal horn of the lateral ventricle, located beneath the inferior border of the amygdala. The AN point, the vertex of the notch in the sagittal direction, is a reliable ventricular landmark in the antero-posterior and infero-superior directions. The medial vertex of the diverticulum, ANm, is a ventricular landmark in the medio-lateral direction. The 'AN system of coordinates' is a reliable system for amygdalar stereotaxy. Stereotaxy of the anterior hippocampus would benefit from other ventricular landmarks. The most lateral point of the main body (HiL) is a landmark for the medio-lateral dimension. Ventriculography and ventricular landmarks should always be used for stereotaxy in primate species.     

Striatal extracellular dopamine levels in rats with haloperidol-induced depolarization block of substantia nigra dopamine neurons

Correlations between substantia nigra (SN) dopamine (DA) cell activity and striatal extracellular DA were examined using simultaneous extracellular single-unit recordings and in vivo microdialysis performed in drug-naive rats and in rats treated repeatedly with haloperidol (HAL). Intact rats treated with HAL for 21-28 d exhibited significantly fewer active DA cells, indicating the presence of depolarization block (DB) in these cells. However, in rats that received surgical implantation of the microdialysis probe followed by a 24 hr recovery period, HAL-induced DA cell DB was reversed, as evidenced by a number of active DA neurons that was significantly higher than that in HAL-treated intact rats and similar to that of drug-naive rats. In contrast, using a modified probe implantation procedure that did not reverse SN DA neuron DB, we found striatal DA efflux to be significantly lower than in controls and significantly correlated with the reduction in DA neuron spike activity. Furthermore, although basal striatal DA efflux was independent of SN DA cell burst-firing activity in control rats, these variables were significantly correlated in rats with HAL-induced DA cell DB. Therefore, HAL-induced DB of SN DA neurons is disrupted by implantation of a microdialysis probe into the striatum using standard procedures. However, a modified microdialysis method that allowed reinstatement of DA neuron DB revealed that the HAL-induced inactivation of SN DA neurons was associated with significantly lower extracellular DA levels in the striatum. Moreover, the residual extracellular DA maintained in the presence of DB may, in part, depend on the burst-firing pattern of the noninactivated DA neurons in the SN.     

Antidepressants are not placebos.

Comments on the article by I. Kirsch and S. J. Lynn (see record 1999-05760-005), which concerned the effects of expectancy in clinical behavior change. Kirsch and Lynn reviewed several meta-analyses of placebo-controlled trials of antidepressants, and examined areas of research in which response expectancies have been shown to affect experience, behavior, and physiology: placebo effects, the effects of false biofeedback on sexual arousal, and the alteration of perceptual and cognitive functions by hypnotic and nonhypnotic suggestion. The present author questions and argues against Kirsch and Lynn's conclusion that apparent drug effects of antidepressants may in fact be a placebo effect, magnified by differences in experienced side effects and the patient's subsequent recognition of the condition to which he or she has been assigned. Among other criticisms, the present author claims that evidence for the absence of the placebo effect in clinical practice effectively argues against its power. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Editors are not blind.

Comments on the continuing debate on anonymous reviewing (see record 1986-18404-001) and notes that the journal's editor decides whether a paper will be published, not the reviewer. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

DRGs are not enough.

Proposes that the federal government conduct research and demonstrations on community support maintenance organizations (CSMOs). Capitation would be given to CSMOs for providing a continuum of comprehensive, rehabilitatively oriented service packages that would reduce the use of inpatient and other costly and restrictive services by seriously or chronically mentally disabled persons. It is concluded that psychological theory, research, and practice can make a contribution to the development of prospective payment alternatives to DRG (diagnosis-related group) based systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prolongation of responses in decentralization supersensitivity

In chronically decentralized nictitating membranes of cats the responses to norepinephrine and to acetylcholine were markedly prolonged. The increased duration was not directly related to the increased amplitude of the contractions. It is likely to be due to a change of the muscle itself.     

Elevated levels of serum lipoprotein(a) and apolipoprotein(a) phenotype are not related to pre-eclampsia

BACKGROUND: Pre-eclampsia might result from a less effective invasion of trophoblast cells in the myometrium, caused by attenuated immunosuppression in the spiral arteries, resulting from inhibition of plasmin-mediated activation of transforming growth factor-beta-like substances. In vitro evidence indicates that lipoprotein(a) is capable of inhibiting plasmin-mediated activation of transforming growth factor-beta. Thus, high plasma levels of lipoprotein(a) might result in increased incidence of preeclampsia. METHODS: The patient group consisted of 39 patients with a history of pre-eclampsia in a previous pregnancy: Forty-seven women without pre-eclampsia in their history and matched for age were the control group. All participants gave their informed consent. In both the patient and control group blood pressure, CRP, urinalysis, cholesterol, HDL-cholesterol, triglycerides, lipoprotein(a) level and apolipoprotein(a) phenotype were determined. RESULTS: None of the participants had elevated CRP levels, excluding acute phase related elevations of lipoprotein(a). Proteinuria was present in 33% of patients and in 11% of controls (p=0.01). However, no relation was observed between proteinuria and Lp(a) level. Median Lipoprotein(a) levels in both groups were equal (300 mg/l vs. 275 mg/l; p=0.48), as well as the apo(a) phenotype distribution in both groups. CONCLUSIONS: Lipoprotein(a) and apolipoprotein(a) phenotype do not contribute significantly to the pathogenesis of pre-eclampsia.     

Restrained eating among adolescents: Dieters are not always bingers and bingers are not always dieters.

This study examined individual differences in the relationships among 3 constructs relevant to restrained eating theory—cognitive restraint (dieting), disinhibition (bingeing), and hunger. Participants were 421 adolescents (158 male, 255 female, and 8 not indicated). Comparisons among subgroups based on scores on the 3 constructs indicated that there were (a) 2 types of frequent dieters—those who follow theoretical predictions and become disinhibited and those who maintain their restraint; (b) 2 types of bingers—those who engage in dieting-induced bingeing and those who are hungry and disinhibited; and (c) 2 types of low-hunger eaters—those who suppress their hunger and those who eat before they experience much hunger. Implications of the results for restrained eating theory are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)