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Biomedical subjects

A Najafi

Publications and source records attributed to A Najafi.

At least 19 recordsLinked to original sources

The natural radioactivity in the bricks used for the construction of the dwelling in Tehran areas of Iran.

This paper presents the finding of a study undertaken to determine the natural radioactivity present in bricks in Tehran. A total of 45 samples of commonly used bricks were collected from various manufacturers and suppliers and analyzed using a shielded HPGe gamma ray spectrometer. The specific activities of (226) Ra, (232) Th, and (40) K were measured in all brick samples, and results ranged from minimum values of 26, 24, and 524 Bq kg(-1) to maximum values of 38, 36, and 820 Bq kg(-1) with mean values of 33, 30, and 700 Bq kg(-1) ,respectively. In general, these activities were comparable to the results of similar studies undertaken in another countries. These activities would suggest that the use of such bricks in construction of dwellings or work places in Tehran is unlikely to give rise to any significant radiation exposure to the occupants.

Air Pollution, Indoor↗

Comparison of the effect of aminophylline and low PEEP vs. high PEEP on EGF concentration in critically ill patients with ALI/ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a serious, often fatal, condition, despite progress in modern critical care treatment. Cytokines play important roles in the pathogenesis of the syndrome, although their roles in the evaluation and outcome have not been clearly elucidated yet. OBJECTIVES: We tested whether serum concentration of epidermal growth factor (EGF), as one of the important inflammatory mediators, changes with time and administration of mechanical ventilation and aminophylline. PATIENTS AND METHODS: Thirty patients [mean (SD): age = 56.6 (17.4) years] with ARDS were enrolled. After diagnosis based on inclusion and exclusion criteria, the patients were intubated and mechanically ventilated. Two hours after ventilation with definite positive end-expiratory pressure (PEEP), aminophylline with a specific dose was started. Serum samples were obtained at five time points of 0, 2, 2.5, 4 and 8 h post-starting PEEP. RESULTS: Serum EGF concentration decreased after mechanical ventilation with PEEP (P < 0.05). The serum EGF concentrations 8 h after intervention was statistically lower in the low PEEP group than in the high PEEP group. The Acute Physiology and Chronic Health Evaluation (APACHE) Pi score and PaO2/FiO2 improved significantly after 8 h (P < 0.05). CONCLUSION: Beneficial effects of mechanical ventilation and aminophylline on APACHE Pi score and PaO2/FiO2 influence serum EGF levels. These findings may have relevance to the development of multisystem organ failure.

APACHE↗

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.

Adenocarcinoma↗

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.

Adenocarcinoma↗

Correlation of intellectual impairment in Parkinson's disease with FDG PET scan.

This study investigated the relationship between regional glucose metabolism with intellectual impairment in patients with Parkinson's disease using statistical parametric mapping. Regional cerebral glucose metabolism using [18F]deoxyglucose (FDG) PET scans were performed on 10 patients with Parkinson's disease. We used the intellectual impairment score from the UPDRS. PET scans were analyzed with SPM96. Patients showed significant positive correlations with left limbic structures such as the cingulate gyrus, parahippocampal gyrus, and medial frontal gyrus. Patients showed significant negative correlations with associative neocortical posterior structures such as bilateral parietal and occipital gyrus. There were significant relationships between regional glucose metabolism and intellectual impairment.

Aged↗

Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex.

OBJECTIVE: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. METHOD: Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. RESULTS: One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. CONCLUSIONS: High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.

Adolescent↗

Increased dopamine activity associated with stuttering.

Position 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 prefrontal 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 presynaptic dopamine system in brain regions that modulate verbalization.

Adult↗

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.

Adult↗

PET and MRI of the thalamus in never-medicated patients with schizophrenia.

OBJECTIVE: This study reports the first paired measurements of glucose metabolism and size of thalamic regions in never-medicated schizophrenic patients using coregistered magnetic resonance imaging (MRI) templates. METHOD: Positron emission tomography with [18F]fluorodeoxyglucose and matching MRI scans were obtained in 20 never-medicated patients with schizophrenia and 15 normal volunteers. Methods for thalamic edge finding, statistical testing of shape differences with chi-square maps, and MRI localization of major thalamic subregions were developed. RESULTS: Patients with schizophrenia showed a diminished metabolic rate in the right thalamus, with a loss of the normal pattern of right greater than left asymmetry. Division into anterior/posterior segments revealed that the left anterior and right posterior showed the decrease. Differences were greater for metabolism in the weighted thalamic area (ratexarea) than for rate per unit area, a finding consistent with reported greater decreases in total neuron number than of neuron density in the thalami of schizophrenic patients. The area of the thalamus was smaller in the patients than in the volunteers, and this difference was greatest in the left anterior region. CONCLUSIONS: The reduced thalamic activity observed in this study lends further support to the concept of deficits in sensory filtering in schizophrenia.

Adult↗

Measures and pitfalls for successful preparation of "no carrier added" asymmetric 6-[18F]fluor-L-dopa from 18F-fluoride ion.

6-[18F]Fluoro-L-dopa (6FD) has been proposed and used for probing cerebral dopamine metabolism by positron emission tomography. Recently a new method for asymmetric synthesis of 6FD has been reported. This method involves synthesis of 6-[18F]fluoro-3,4-dimethoxybenzylbromide which is reacted with (S)-1-Boc-2-tert-butyl-3-methyl-4-imidazolidinone. The resulting alkylated compound is then hydrolyzed with hydriodic acid to produce 6FD. This method has been used to produce 6FD and several critical steps that required attention found, in addition to some modification for successful 6FD production. 6FD is prepared in 6-13% radiochemical yield (decay not corrected) after HPLC purification with a production time of 85 min.

Chromatography, High Pressure Liquid↗

Enhancement of seminiferous tubular growth and spermatogenesis in testes of rats recovering from early hypothyroidism: a quantitative study.

Testicular weight and DNA content were markedly reduced (63 and 69%) in weanling Long-Evans rat pups rendered hypothyroid from birth by administration of propylthiouracil (PTU), a reversible goitrogen. These growth deficits worsened to > 80% by continuing hypothyroidism beyond weaning, to days 50 and 90. Recovery of thyroid function, brought about by discontinuing PTU at weaning, resulted in a paradoxical stimulation of testis growth, amounting to increased weight (40%), DNA content (60%) and size by 90 days, compared to age-matched controls. In the 25-day or older hypothyroid rats, testicular structure was immature and spermatogenesis markedly delayed, as evident by closed lumen and significantly reduced diameter of seminiferous tubules (38%), thickness of germinal layer (70%), and number of primary spermatocytes (86%), compared to control. Hypothyroidism did not alter the number of tubules per testis cross section. In the 90-day recovery rats, numbers of seminiferous tubules were unchanged but tubular diameter was significantly (20%) larger than in controls and spermatogenesis appeared very active as indicated by significantly increased germinal layer thickness (22%) and total number and density of primary spermatocytes (55% and 40%). The results show that although postnatal hypothyroidism is deleterious for testicular growth and spermatogenesis, recovery from this condition leads to enhanced seminiferous tubular growth and spermatogenesis.

Animals↗

Clozapine effects on glucose metabolic rate in striatum and frontal cortex.

Eighteen patients with schizophrenia had cerebral metabolic rates assessed with positron emission tomography during a double-blind, placebo-controlled crossover study of clozapine treatment. Relative metabolic rates were increased in the basal ganglia, especially on the right side. In the frontal lobe, metabolic rates were lowered, more on the left than on the right. The anterior nuclei of the thalamus also showed lower metabolic rates after clozapine. We have previously observed patients with schizophrenia to have low metabolic rates in the basal ganglia and to lack the normal right > left asymmetry; in this study, clozapine normalized striatal activity. In the frontal lobe, asymmetry was normalized, but hypofrontal function was, if anything, exaggerated. This effect in the frontal lobe was not observed with haloperidol in earlier studies. The cortical effects of clozapine may be related to its unique clinical properties and suggest important differences between typical and atypical antipsychotic drugs.

Adult↗

Preparation and in vitro evaluation of "no-carrier-added" 18F-labeled biotin.

This paper will describe the preparation of "no-carrier-added" 18F-labeled biotin where the radiolabel bound to an aromatic moiety is described. This has been accomplished by preparation of [18F]fluorobenzylbromide (yield 20-30%) and its reaction with biotin-LC-hydrazide. This yielded "no-carrier-added" radiolabeled biotin (5-10%) which was then purified by reversed phase HPLC. The pure product was found to bind to avidin, thereby demonstrating retention of its biological integrity. Thus this product is potentially useful for imaging tumor tissue following injection of avidin coupled MoAbs.

Avidin↗

Preparation and preliminary biological evaluation of [18F]NCQ-115: a new selective reversible dopamine D2 receptor ligand.

18F-labeled dopamine D2 antagonist, NCQ-115 ((+)-(R)-5-bromo-N-((1-(fluorobenzyl)-2-pyrrolidinyl)-methyl-2,3- dimethoxybenzamide), was successfully prepared using a remotely controlled system. [18F]Fluoride was reacted with the trifluoromethanesulfonate salt of 4-(trimethylamino)benzaldehyde. The product was first reduced with LAH, and then reacted with thionyl bromide to yield 18F-labeled 4-fluorobenzylbromide. [18F]4-Fluorobenzylbromide was then reacted with the pyrrolidie precursor (NCQ-282) to yield the product [18F]NCQ-115 contaminated with unreacted starting material. The product was purified by reverse phase chromatography yielding [18F]NCQ-115 with a specific activity of more than 1400 Ci/mmol. Autoradiographic and biodistribution data following injection of [18F]NCQ-115 in rats revealed the regional uptake of striatum/cerebellum to be 3.2 at 30 min post-injection.

Animals↗

Cortical-striatal-thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients.

OBJECTIVE: The cortical-striatal-thalamic circuit modulates cognitive processing and thus may be involved in the cognitive dysfunction in schizophrenia. The imaging of metabolic rate in the structures making up this circuit could reveal the correlates of schizophrenia and its main symptoms. METHOD: Seventy male schizophrenic patients underwent [18F]-fluorodeoxyglucose positron emission tomography after a period of at least 4 weeks during which they had not received neuroleptic medication and were compared to 30 age-matched male normal comparison subjects. RESULTS: Analyses revealed decreased metabolism in medial frontal cortex, cingulate gyrus, medial temporal lobe, corpus callosum, and ventral caudate and increased metabolism in the left lateral temporal and occipital cortices in the schizophrenic cohort. Consistent with previous studies, the schizophrenic group had lower hypofrontality scores (ratios of lateral frontal to occipital metabolism) than did comparison subjects. The lateral frontal cortical metabolism of schizophrenic patients did not differ from that of comparison subjects, while occipital cortical metabolism was high, suggesting that lateral hypofrontality is due to abnormalities in occipital rather than lateral frontal activity. Hypofrontality was more prominent in medial than lateral frontal cortex. Brief Psychiatric Rating Scale (BPRS) scores, obtained for each schizophrenic patient on the scan day, were correlated with regional brain glucose metabolic rate. Medial frontal cortical and thalamic activity correlated negatively with total BPRS score and with positive and negative symptom scores. Lateral frontal cortical metabolism and hypofrontality scores did not significantly correlate with negative symptoms. Analyses of variance demonstrated a reduced right greater than left asymmetry in the schizophrenic patients for the lateral cortex as a whole, with simple interactions showing this effect specifically in temporal and frontal cortical regions. CONCLUSIONS: Low metabolic rates were confirmed in medial frontal cortical regions as well as in the basal ganglia, consistent with the importance of the cortical-striatal-thalamic pathways in schizophrenia. Loss of normal lateralization patterns was also observed on an exploratory basis. Correlations with negative symptoms and group differences were more prominent in medial than lateral frontal cortex, suggesting that medial regions may be more important in schizophrenic pathology.

Adolescent↗

The evaluation of 186Re-labeled antibodies using N2S4 chelate in vitro and in vivo using tumor-bearing nude mice.

We have recently described a method for radiolabeling monoclonal antibodies, with metallic radionuclides using a new chelating agent N2S3. Using this chelate the monoclonal antibodies Lym-1 and B72.3 were labeled with 186Re and their biological integrity was evaluated in vitro and in vivo. 186Re-labeled antibodies using N2S4 methodology were found to be stable in human serum and retained their immunoreactivity. Intravenous administration of 0.5 mCi 186Re-labeled antibodies resulted in partial or complete regression of tumor tissue in mice.

Animals↗

Synthesis and preliminary evaluation of a new chelate N2S4 for use in labeling proteins with metallic radionuclides.

The successful attachment of various metallic radionuclides such as 99mTc to monoclonal antibodies for targeting tumor tissue in vivo depends upon the development and use of suitable bifunctional chelating agents. We have successfully synthesized a new N2S4 (compound 4) chelate. This chelate forms a stable complex with 99mTc and is capable of coupling to different proteins. The N2S4 compound is quite stable if kept as a hydrochloride salt and is coupled to antibody under neutral conditions with better than 95% efficiency without the loss of immunoreactivity.

Antibodies, Monoclonal↗

Dose dependency of 99mTc disofenin (DISIDA) in biliary tract imaging.

Data presented on pharmacological effects of gadolinium labeled disofenin (DISIDA) upon administration of large mass amounts suitable to produce MR contrast prompted us to investigate these effects with technetium labeled DISIDA. A variable mass of [99mTc]Tc-DISIDA, 0.05-100 mg, was administered to rabbits. The effective half life in the liver did not vary significantly for doses between 0.05 and 5 mg, with an average of about 17 min. However, the effective half life increased to about 300 min for a 100 mg dose of DISIDA.

Animals↗