Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment

Involvement of the dopaminergic system has been suggested in patients suffering from attention deficit hyperactivity disorder (ADHD) since the symptoms can be successfully treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). This study reports the findings on the status of the DAT in adults with ADHD before and after commencement of treatment with methylphenidate, as measured using [99mTc]TRODAT-1. Seventeen patients (seven males, ten females, aged 21-64 years, mean 38 years) were examined before and after the initiation of methylphenidate treatment (3x5 mg/day). All subjects were injected with 800 MBq [99mTc]TRODAT-1 and imaged 3 h p.i. Single-photon emission tomography (SPET) scans were acquired using a triple-headed gamma camera. For semiquantitative evaluation of the DAT, transverse slices corrected for attenuation were used to calculate specific binding in the striatum, with the cerebellum used as background [(STR-BKG)/BKG]. Data were compared with an age-matched control group. It was found that untreated patients presented with a significantly increased specific binding of [99mTc]TRODAT-1 to the DAT as compared with normal controls [(STR-BKG)/BKG: 1.43+/-0.18 vs 1.22+/-0.06, P<0.001]. Under treatment with methylphenidate, specific binding decreased significantly in all patients [(STR-BKG)/BKG: 1.00+/-0.14, P<0.001]. Our findings suggest that the number of DAT binding sites is higher in drug-naive patients suffering from ADHD than in normal controls. The decrease in available DAT binding sites under treatment with methylphenidate correlates well with the improvement in clinical symptoms. The data of this study help to elucidate the complex dysregulation of the dopaminergic neurotransmitter system in patients suffering from ADHD and the effect of treatment with psychoactive drugs.     

Assessment of Oxidative, Inflammatory, and Fibrinolytic Biomarkers and DNA Strand Breakage in Hypercholesterolemia

The aim of this study was to assess the levels of oxidative, inflammatory, and fibrinolytic biomarkers as well as DNA strand breakage in hypercholesterolemic subjects. Fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid, total protein, albumin, apolipoprotein (Apo) A, Apo B, advanced oxidation protein products (AOPP), increased ischemia-modified albumin (IMA), ―SH, NOx, IL-6, and D-dimer levels were assessed, and DNA strand breakage was evaluated using comet assay in 38 patients with hypercholesterolemia and 20 healthy controls. Total cholesterol, triglycerides, LDL cholesterol, Apo A, Apo B, AOPP, IMA, IL-6, and D-dimer concentrations were significantly higher in subjects with hypercholesterolemia. However, NOx and plasma ―SH group concentrations were lower in hypercholesterolemic subjects, while no significant differences were observed with respect to DNA strand breakage between the two groups. Hypercholesterolemia is related to oxidative stress and inflammation. Accordingly, AOPP concentration was higher in subjects with hypercholesterolemia, and we speculate that AOPP can reflect the enhancement of protein oxidation and inflammation.     

Association between periodontitis and glycated hemoglobin levels in individuals living in rural Southern Brazil

Clinical Oral Investigations - To estimate the prevalence of prediabetes in individuals with moderate or severe periodontitis and to verify the association between periodontitis and glycated...     

Optimized threshold for serum HCV RNA to predict treatment outcomes in hepatitis C patients receiving peginterferon alfa‐2a/ribavirin

Summary. It is unclear whether the current threshold for ‘high’ hepatitis C virus (HCV) RNA level (800 000 IU/mL) is optimal for predicting sustained virological response (SVR). We retrospectively analysed pretreatment HCV RNA levels and SVR rates in 1529 mono‐infected and 176 HIV–HCV co‐infected patients treated with peginterferon alfa‐2a (40 kD) plus ribavirin. We improved the threshold for differentiating low and high viral load by fitting semiparametric generalized additive logistic regression models to the data and constructing receiver operating characteristics curves. Among HCV genotype 1 mono‐infected patients, the difference in SVR rates between those with low and high baseline HCV RNA levels was 27% (70%vs 43%) when 400 000 IU/mL was used and 16% (59%vs 43%) when 800 000 IU/mL was used. In HIV–HCV genotype 1 co‐infected patients, the difference was 51% (71%vs 20%) when 400 000 IU/mL was used and 43% (61%vs 18%) when 800 000 IU/mL was used. A lower threshold (200 000 IU/mL) was identified for genotype 1 mono‐infected patients with ‘normal’ alanine aminotransferase (ALT) levels. No threshold could be identified in HCV genotype 2 or 3 patients. A threshold HCV RNA level of 400 000 IU/mL is optimal for differentiating high and low probability of SVR in genotype 1‐infected individuals with elevated ALT.     

Clinical applications of single photon emission tomography in neurology. 2. Dementia, psychoses, inflammation, skull and brain injuries

This article gives in his second part a critical review of the clinical applications of SPECT with perfusion markers and receptor ligands in dementing disorders and psychosis. In addition this review discusses clinical applications of SPECT investigations with perfusion markers in inflammatory diseases of the central nervous system and in brain trauma.     

Imaging of the dopaminergic system in parkinsonism with SPET.

Parkinsonism is a feature of various neurodegenerative diseases. Since it is well known that the dopaminergic system plays a major role in parkinsonism, numerous reports have focused on the assessment of the dopaminergic system in vivo. While the use of positron emission tomography (PET) for routine application is still hampered by its limited availability, single photon emission tomography (SPET) has been shown to deliver comparable results to PET in clinical settings. In recent years SPET investigations of the dopamine transporter and of the dopamine D2-like receptors have provided valuable information about the pre- and postsynaptic dopaminergic system in parkinsonism. This article briefly reviews the literature dealing with SPET imaging in parkinsonism and specifically addresses the ligands used, the methodology applied, and the current major clinical applications.     

Striatal dopamine D2 receptor binding of risperidone in schizophrenic patients as assessed by 123I-iodobenzamide SPECT: a comparative study with olanzapine

The aim of this investigation was to compare the degree of striatal dopamine-(D2) receptor blockade by two atypical antipsychotic drugs, risperidone and olanzapine. The percentage of D2 receptor occupancy during treatment was calculated by comparing the results of 123I-iodobenzamide SPECT with those from healthy control subjects. Twenty inpatients suffering from schizophrenia or schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with clinically recommended doses of risperidone and compared with 13 inpatients treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade correlated strongly for both risperidone (Pearson r = -0.86, p = 0.0001) and olanzapine (Pearson r = -0.77, p = 0.002). There was no significant difference between the D2 receptor occupancy of the two substances when given in the clinically recommended dose range (unpaired t-test, t = -0.112, p = 0.911).