Ahmad Najafi

Increased dopamine activity associated with stuttering

POSITRON emission tomography using 6-FDOPA as a marker of presynaptic dopaminergic activity was used to investigate the role of the dopamine system in stuttering. Three patients with moderate to severe developmental stuttering were compared with six normal controls. Stuttering subjects showed significantly higher 6-FDOPA uptake than normal controls in medial pre-frontal cortex, deep orbital cortex, insular cortex, extended amygdala, auditory cortex and caudate tail. Elevated 6-FDOPA uptake in ventral limbic cortical and subcortical regions is compatible with the hypothesis that stuttering is associated with an overactive pre-synaptic dopamine system in brain regions that modulate verbalization.

Decreasing striatal 6-FDOPA uptake with increasing duration of cocaine withdrawal

It has been hypothesized that a decrease in dopaminergic presynaptic activity during abstinence or withdrawal is related to relapse in cocaine-dependent subjects (Dackis and Gold 1985; Markou and Koob 1991). This study measured striatal 6-fluorodopa (6-FDOPA) uptake, an index of dopaminergic presynaptic activity, using positron emission tomography (PET) in 11 drug-free cocaine addicts compared to eight normal subjects. Middle abstinence cocaine addicts (n = 5, off cocaine 11–30 days) had significantly lower striatal 6-FDOPA uptake compared to normal controls or early abstinence cocaine addicts (n = 6, off cocaine 1–10 days). The cocaine-dependent subjects (n = 11) showed a significant negative correlation between days off cocaine and striatal 6-FDOPA uptake. The results suggest that during abstinence from cocaine there is a delayed decrease in dopamine terminal activity in the striatum.

Effect of vasodilator hydralazine on tumor microvascular random flow and blood volume as measured by intravoxel incoherent motion (IVIM) weighted MRI in conjunction with Gd-DTPA-Albumin enhanced MRI.

We studied the effect of hydralazine on tumor blood volume fraction and microvascular random flow velocity magnitude by IVIM weighted MRI in conjunction with dynamic Gd-DTPA-Albumin enhanced MRI. Blood volume fraction maps were obtained from the dynamic Gd-DTPA-Albumin enhanced MRI measurements. The average blood volume fraction of R3230 AC adenocarcinoma decreased from 0.125 +/- 0.022 (s.d.) ml/g to 0.105 +/- 0.018 (s.d.) ml/g (p < 0.001) after the administration of hydralazine at a dose of 5 mg/kg. The microvascular random flow velocity magnitude maps were obtained from the IVIM weighted MRI signals by utilizing the Gd-DTPA-Albumin measured blood volume fractions as an input in the compartmental modeling analysis of the IVIM weighted MRI signal. The random-directional microvascular flow induced MRI signal attenuation was separated from the molecular diffusion induced signal attenuation. Flow induced attenuation was more significant after the administration of hydralazine. The mean microvascular random flow velocity magnitude increased from 0.52 +/- 0.15 (s.d.) mm/sec to 0.73 +/- 0.23 (s.d.) mm/sec (p < 0.05) in the presence of the above blood volume fraction change.

Selective Thrombosis of Tumor Blood Vessels in Mammary Adenocarcinoma Implants in Rats

Adenocarcinomas in rats and humans frequently contain perivascular, degranulating mast cells that release heparin. Protamine is a low-molecular weight, cationic polypeptide that binds avidly to heparin and neutralizes its anticoagulant properties. We hypothesized that mast-cell heparin functions as a localized anticoagulant that modulates hemostasis and blood perfusion in tumors. Consequently, systemically administered protamine should be able to neutralize the endogenous heparin within tumors, thereby inducing selective thrombosis of blood vessels within tumors. Here we demonstrate with magnetic resonance imaging (MRI) that an intravenous dose of protamine labeled with gadolinium accumulated within the parenchyma of subcutaneous implants of a mammary adenocarcinoma in Fischer 344 rats. Moreover, we show with dynamic contrast enhanced MRI that sequential intravenous doses of protamine in 12 tumor-bearing rats resulted in significantly decreased signal enhancement kinetics (blood perfusion) of the tumor. This functional impairment of MRI signal enhancement was accompanied by histological evidence of thrombosis in the blood vessels within the tumor. There was no histological evidence of thrombosis within normal liver, kidney, lung, spleen, or adjacent muscle of tumor-bearing animals that received protamine treatment or in the tumors of animals that had not been pretreated with protamine. On the basis of these results, we conclude that protamine accumulates within adenocarcinoma implants and induces selective thrombosis of blood vessels within the tumor, probably by neutralizing the endogenous heparin within tumors.