Striatal dopamine transporter density in major depression

Rationale: There are no previous data available regarding [¹²³I]β-CIT binding to the dopamine transporter sites in the basal ganglia in depressed patients. Objective: The present study tested the hypothesis that the brain DAT density in depressed patients is lower than that in matched healthy controls. Methods: Fifteen drug-naive outpatients with major depression and 18 healthy controls were investigated using single photon emission computerized tomography (SPECT) with a high-affinity dopamine transporter specific radioligand, ¹²³I-labeled β-CIT (2β-carbomethoxy-3β-(4-iodophenyl)-tropane). Results: We found a significantly higher [¹²³I]β-CIT uptake in both sides of the basal ganglia in patients with major depression than in the controls (Mann-Whitney U-test, P = 0.002 on the right and P = 0.003 on the left). Conclusions: The radioligand uptake reflecting the DAT density was significantly higher among the patients than in the controls. This finding is unexpected, since it is generally believed that monoaminergic neurotransmission is lower in depression, and therefore it could be assumed that a reduction in dopamine transmission would lead to secondary down-regulation of DAT density. However, it is possible that up-regulation of the DAT may be the primary alteration, which leads to lower intrasynaptic dopamine concentration and to lower dopamine neural transmission. Received: 20 October 1998/Final version: 25 January 1999     

Electrophysiological indices of acute effects of ethanol on involuntary attention shifting

Dose-related effects of ethanol (placebo, 0.30, and 0.60 g/kg) on behavioral and event-related brain potential (ERP) indices of involuntary attention shifting of audition were investigated. ERPs were recorded from 11 healthy social drinkers during a forced-choice reaction-time (RT) task. Subjects were presented with 100 and 200 ms tones (P = 0.50 for each) with a constant inter-stimulus interval (ISI) of 1 s. The task was to press either of two buttons, depending on the tone duration. The majority of the tones (“standards”) were of 700 Hz (P = 0.82). Occasionally, however, the frequency of the tones changed, deviating either slightly (750 Hz), moderately (900 Hz), or widely (1200 Hz; P = 0.06 for each) from the standard frequency. In accordance with previous findings, the task-irrelevant frequency deviations prolonged the RT. This RT prolongation was attenuated by alcohol with the 0.3 g/kg dose, thus suggesting less distraction by irrelevant stimulus deviations under the influence of ethanol. Furthermore, the P3a, reflecting involuntary attention shifting, was suppressed by alcohol even with the 0.3 g/kg dose. These findings demonstrate a detrimental effect of alcohol on involuntary attention shifting, evident with doses considerably smaller than previously described, and still juridically acceptable in road traffic in most countries. Received: 19 December 1997/Final version: 26 May 1998     

Neuroleptic malignant syndrome during low dosed neuroleptic medication in first-episode psychosis: a case report

 Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal side-effect of antipsychotic drug therapy, especially of dopamine receptor antagonists. As a dose relationship has been postulated, low dose neuroleptization would be expected to help to avoid this side-effect. In contrast, we report on a 21-year-old female following low dose fluphenazine treatment with 2.5 mg/day. The patient recovered from NMS after 3 days of dantrolene administration. Eventually, remission from psychotic symptoms was achieved with clozapine. At 8-month follow-up, psychopathology remained stable and there were no more signs of NMS. Received: 8 July 1998 / Final version: 6 November 1998     

Transport of manganese via the olfactory pathway in rats: dosage dependency of the uptake and subcellular distribution of the metal in the olfactory epithelium and the brain

The dosage dependency of the uptake of Mn from the olfactory epithelium via olfactory neurons into the brain was studied after intranasal administration of the metal in rats. The results indicate that the Mn transport is saturable both regarding the uptake into the olfactory epithelium and the transfer to the olfactory bulb. Further, our data indicate that Mn moves relatively freely from the olfactory bulb to the olfactory cortex at an amount dependent on the level of influx into the bulb. The transport to the rest of the brain was related to the amounts in the olfactory bulb and the olfactory cortex, but the relative proportion reaching this area increased with increasing doses. Cell fractionations showed that the Mn was present both in the cytosol and in association with various cell constituents. Gel filtrations of the cytosol on a Superdex 30 column showed that about 20% of the Mn in the brain and about 3% in the olfactory epithelium was eluted together with high-molecular-weight materials (MW > 10,000), whereas the rest was eluted in the total volume and may represent unbound metal. It is likely that the metal has been loosely associated with protein(s) or other constituents at the application to the column, but that this association is too loose to be retained during the passage through the column. Our results show that the olfactory neurons provide a pathway with a considerable capacity to transport Mn into the brain. We propose that the neurotoxicity of inhaled Mn is related to an uptake via this route.     

Sea snake Hydrophis cyanocinctus venom. I. Purification, characterization and N-terminal sequence of two phospholipases A2.

Two phospholipases A2 (PLA2, H1 and H2) from sea snake Hydrophis cyanocinctus venom were purified to homogeneity in a single step using reversed-phase high performance liquid chromatography on a Nucleosil 7C18 column. The molecular weights of H1 and H2, as estimated by MALDI MS, were 13588.1 and 13247.2 Da, respectively. The N-terminal 60 amino acid residues were determined by direct automated Edman degradation analysis. Since both PLA2s show close sequence homologies to those of PLA2s from other Elapid snakes (60-84%) they have been tentatively classified as belonging to group-IA and Asp-49 phospholipases A2. Despite the sequence variation (18%) between H1 and H2, their general structural organization is very similar as shown by their clearly related CD spectra. Furthermore, both enzymes are quite thermostable (60-65 degrees C) as determined by temperature variable CD spectra, indicating that the enzymes contain compact folded structure, mainly based on the core structure of disulfide bridges. However, the major PLA2 (H1) shows higher toxicity to albino rats (LD50 i.p. 0.04 mg/kg) and purification resulted in 18-fold increase in toxicity over the crude or whole venom (LD50 i.p. 0.80 mg/kg). H1 also shows edema-inducing and indirect haemolytic but no haemorrhagic activity. Unlike the toxic PLA2-H1, enzyme H2 was not toxic to albino rats but showed edema-inducing and indirect haemolytic activities.     

What is the price of perfection? The hidden costs of using detailed assessment instruments to measure alcohol consumption

OBJECTIVE: This article describes results from a study investigating the effects of using long assessment instruments on attrition rates in mailed-out surveys. METHOD: Participants were randomly assigned to receive one of two versions of a mailed-out survey; one version incorporated a detailed assessment of drinking using the Timeline Follow back method (TLFB; n = 46) and the other employed a brief graduated frequency measure of alcohol consumption (n = 49). RESULTS: 29% fewer respondents who received the TLFB returned any of their survey materials as compared to those respondents who received just the graduated frequency measure (22% vs 51%). CONCLUSIONS: In some situations, e.g., mailed-out surveys, employing detailed survey instruments may not be justified as the increased respondent burden may result in increased attrition rates.     

Energy metabolism in the involuting mammary gland

A strong and coordinated upregulation of the glycolytic, glutaminolytic and pentose phosphate pathway enzymes occurs during the onset of lactation in the normal mouse mammary gland. Induction of apoptosis by removing the pups led to an inactivation of the same enzymes with different time courses. While the ATP-consuming glycolytic 6-phosphofructo 1-kinase and mitochondrial bound hexokinase still remained high on days one and two of involution, the ATP-regenerating pyruvate kinase was immediately reduced. The enzymes of the pentose phosphate and glutaminolytic pathway were inactivated on the first two days of involution. In accordance with such an inactivation of the enzymes ATP, GTP, UTP, ADP, NAD NADH and lactate concentrations decreased. The synthetic product of UTP, UDP-N-acetylglucosamine, increased. AMP was found in the milk, not in the epithelial cells. The inactivation of the enzymes was caused by partial proteolysis or by a loss of the intact proteins from the cytosol without signs of proteolysis.     

A cortisol suppression dose-response comparison of budesonide in controlled ileal release capsules with prednisolone

AIM: To assess the systemic effect of oral budesonide, given as Entocort controlled ileal release capsules, over a dose range of 3-15 mg/day, compared with that of a moderate dose (20 mg/day) of prednisolone. METHODS: Twenty four healthy subjects were given 3, 9 or 15 mg budesonide or 20 mg prednisolone once daily, or 4.5 mg budesonide b.d., or placebo for 5 days in a randomized, double-blind crossover study. The area under the curve (AUC) of plasma cortisol concentration and the amount of cortisol excreted in the urine were monitored. RESULTS: Both plasma and urine cortisol suppression showed a dose-response for the daily doses of budesonide. Prednisolone, 20 mg, suppressed plasma cortisol (AUC) statistically significantly more than 15 mg budesonide (P = 0.014), and 3 mg budesonide statistically significantly more than placebo (P = 0.010). No difference in AUC was detected between 9 mg and 4.5 mg budesonide b.d. Similar results for budesonide vs. placebo were obtained from urine cortisol excretion data. However, prednisolone affected urine cortisol less than it affected plasma cortisol. CONCLUSION: After 5 days of administration, budesonide controlled ileal release capsules, in both clinical (9 mg/day) and high doses (15 mg/day), affected plasma cortisol less than a moderate (20 mg/day) dose of prednisolone.     

Partial models in fixed prosthodontics

In general there is consensus regarding the required criteria for crown- and bridge restorations. However, the variety in methods used for their fabrication is large. Textbooks and courses tend to advocate the use of full arch impressions without supplying objective data indicating better clinical behaviour of these restorations compared with the use of quadrant impressions. This article presents advantages, disadvantages, indication and essential steps when using quadrant models.     

The rate constant of photoinhibition, measured in lincomycin-treated leaves, is directly proportional to light intensity

Pumpkin leaves grown under high light (500-700 micromol of photons m-2.s-1) were illuminated under photon flux densities ranging from 6.5 to 1500 micromol.m-2.s-1 in the presence of lincomycin, an inhibitor of chloroplast protein synthesis. The illumination at all light intensities caused photoinhibition, measured as a decrease in the ratio of variable to maximum fluorescence. Loss of photosystem II (PSII) electron transfer activity correlated with the decrease in the fluorescence ratio. The rate constant of photoinhibition, determined from first-order fits, was directly proportional to photon flux density at all light intensities studied. The fluorescence ratio did not decrease if the leaves were illuminated in low light in the absence of lincomycin or incubated in darkness in the presence of lincomycin. The constancy of the quantum yield of photoinhibition under different photon flux densities strongly suggests that photoinhibition in vivo occurs by one dominant mechanism under all light intensities. This mechanism probably is not the acceptor side mechanism characterized in the anaerobic case in vitro. Furthermore, there was an excellent correlation between the loss of PSII activity and the loss of the D1 protein from thylakoid membranes under low light. At low light, photoinhibition occurs so slowly that inactive PSII centers with the D1 protein waiting to be degraded do not accumulate. The kinetic agreement between D1 protein degradation and the inactivation of PSII indicates that the turnover of the D1 protein depends on photoinhibition under both low and high light.