sodium-pertechnetate-tc-99m and Parkinson-Disease

Oesophageal function was examined by radionuclide transit measurements in 15 patients with severe autonomic deficiency and orthostatic hypothension and 23 healthy volunteers. Seven of the patients were re-examined after treatment for 3 weeks with fludrocortisone acetate (Florinef). Six patients and five control subjects were evaluated before and after i.v. administration of atropine. The mean transit time (MTT) was prolonged (P less than 0.007) and the residual activity increased (P = 0.038) in the patients compared with the control group. Prolonged MTT was associated with oesophageal symptoms. Treatment of orthostatic hypotension with fludrocortisone acetate significantly reduced MTT. Atropine increased MTT and residual activity. The increase in heart rate after atropine was correlated in the patients with MTT before treatment. The results demonstrate the frequent presence of impaired oesophageal function in patients with severe autonomic dysfunction, irrespective of aetiology. The impairment seems to be closely related to parasympathetic insufficiency. The improvement after fludrocortisone may suggest an influence of ion balance on oesophageal function in these patients.

Topics: Adult; Aged; Atropine; Autonomic Nervous System Diseases; Diabetic Neuropathies; Esophagus; Female; Fludrocortisone; Gastrointestinal Transit; Humans; Hypotension, Orthostatic; Male; Middle Aged; Parkinson Disease; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Time Factors

The present work evaluated whether the prepared nanoparticles (NPs) would be able to target the drug to the brain by a non-invasive nasal route enhancing its bioavailability.. Bromocriptine (BRC) chitosan NPs (CS NPs) were prepared by ionic gelation method. The biodistribution, pharmacokinetic parameters and dopamine concentration was analysed by ultra-HPLC/mass spectrometry method. The histopathological examination in haloperidol-induced Parkinson's disease in mice model following intranasal (i.n.) administration was evaluated.. BRC was found stable in all exposed conditions and the percentage accuracy observed for intra-day and inter-day batch samples ranged from 90.5 to 107% and 95.3 to 98.9% for plasma and brain homogenates, respectively. BRC-loaded CS NPs showed greater retention into the nostrils (42 ± 8.5% radioactivity) for about 4 h, whereas the 44 ± 7.5% could be retained up to 1 h for BRC solution. The brain:blood ratios of 0.96 ± 0.05 > 0.73 ± 0.15 > 0.25 ± 0.05 of BRC-loaded CS NPs (i.n.) > BRC solution (i.n.) > BRC-loaded CS NPs (intravenous), respectively, at 0.5 h indicated direct nose-to-brain transport bypassing blood-brain barrier. BRC-loaded CS NPs administered intranasally showed significantly high dopamine concentration (20.65 ± 1.08 ng/ml) as compared to haloperidol-treated mice (10.94 ± 2.16 ng/ml) (p < 0.05). Histopathology of brain sections showed selective degeneration of the dopaminergic neurons in haloperidol-treated mice which was markedly reverted by BRC-loaded CS NPs.. Nanoparticulate drug delivery system could be potentially used as a nose-to-brain drug delivery carrier for the treatment of Parkinson's disease.

Topics: Administration, Intranasal; Animals; Antiparkinson Agents; Biological Availability; Biological Transport; Blood-Brain Barrier; Brain; Bromocriptine; Chitosan; Chromatography, High Pressure Liquid; Disease Models, Animal; Dopamine; Drug Delivery Systems; Female; Male; Mass Spectrometry; Mice; Nanoparticles; Nasal Mucosa; Parkinson Disease; Radiopharmaceuticals; Sodium Pertechnetate Tc 99m; Tissue Distribution

The primary aim of this study was to investigate the potential use of chitosan nanoparticles as a delivery system to enhance the brain targeting efficiency of bromocriptine (BRC) following intranasal (i.n.) administration. The BRC loaded chitosan nanoparticles (CS NPs) were prepared by ionic gelation of CS with tripolyphosphate anions. These NPs had a mean size (161.3 ± 4. 7 nm), zeta potential (+40.3 ± 2.7 mV), loading capacity (37.8% ± 1.8%) and entrapment efficiency (84.2% ± 3.5%). The oral administration of haloperidol (2mg/kg) to mice produced typical Parkinson (PD) symptoms. Catalepsy and akinesia outcomes in animals receiving BRC either in solution or within CS NPs showed a reversal in catalepsy and akinesia behavior when compared to haloperidol treated mice, this reversal being specially pronounced in mice receiving BRC loaded CS NPs. Biodistribution of BRC formulations in the brain and blood of mice following i.n. and intravenous (i.v.) administration was performed using optimized technetium labeled (99mTc-labeled) BRC formulations. The brain/blood ratio of 0.47 ± 0.04, 0.69 ± 0.031, and 0.05 ± 0.01 for BRC solution (i.n.), BRC loaded CS NPs (i.n.) and (i.v.) respectively, at 0.5h are suggestive of direct nose to brain transport bypassing the blood-brain barrier. Gamma scintigraphy imaging of mice brain following i.v. and i.n. administrations were performed to determine the localization of drug in brain. The drug targeting index and direct transport percentage for BRC loaded CS NPs following i.n. route were 6.3 ± 0.8 and 84.2% ± 1.9%. These encouraging results confirmed the development of a novel non-invasive nose to brain delivery system of BRC for the treatment of PD.

Topics: Administration, Intranasal; Animals; Antiparkinson Agents; Behavior, Animal; Blood-Brain Barrier; Brain; Bromocriptine; Catalepsy; Chitosan; Disease Models, Animal; Drug Compounding; Drug Delivery Systems; Hypokinesia; Injections, Intravenous; Male; Mice; Nanoparticles; Neurons; Parkinson Disease; Radionuclide Imaging; Random Allocation; Sodium Pertechnetate Tc 99m; Tissue Distribution

In this study, we evaluated the ability of submandibular gland scintigraphy to predict the prognosis of peripheral facial nerve paralysis.. Submandibular gland scintigraphy was performed in 78 patients with acute peripheral facial nerve paralysis. After injection of 180-370 MBq [99mTc]pertechnetate, serial 1-min images were acquired for 25 min. At 15 min after injection of radionuclide, ascorbic acid was administered intraorally to stimulate salivary secretion. Regions of interest were set manually on both submandibular glands, and time-activity curves were generated. The ratios of peak count density (PCR) and washout (WR) of the affected side to the normal side were calculated. Parameters of > or = 0.8 suggested normal affected submandibular function and indicated a good prognosis.. Complete recovery of facial nerve paralysis was observed in 52 of 78 patients. The sensitivity, specificity and accuracy of PCR for a good prognosis were 79%, 50% and 69%, and those of WR were 85%, 77% and 82%, respectively. Positive and negative predictive values for a good prognosis were 76% and 54% in PCR and 88% and 71% in WR, respectively. When WR obtained within 14 days of the onset was used, positive and negative predictive values for a good prognosis were 94% and 73%, respectively. None of the eight patients who had values of <0.8 for both parameters within 14 days of the onset recovered completely.. Submandibular gland scintigraphy can serve as a reliable indicator to predict the prognosis of acute peripheral facial nerve paralysis in its early symptomatic period.

Topics: Acute Disease; Adolescent; Adult; Aged; Ascorbic Acid; Child; Child, Preschool; Facial Paralysis; Female; Humans; Male; Middle Aged; Parkinson Disease; Predictive Value of Tests; Prognosis; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Sodium Pertechnetate Tc 99m; Submandibular Gland

Left ventricular (LV) function was continuously monitored using a radionuclide detector (VEST) after intravenous injection of 25 mCi technetium-99m labelled red blood cells in nine patients with Parkinson's disease and postural hypotension (group 1) and ten patients with Parkinson's disease but without postural hypotension (group 2). LV function and blood pressure were monitored in the supine position for 15 min (period A), upon changing posture from the supine to the upright position for 10 min (period B), and upon returning to the supine position for 10 min (period C). In group 1, the passage from period A to period B induced a significant decrease in end-diastolic volume, end-systolic volume and ejection fraction (all P < 0.01). In group 2, ejection fraction increased (P < 0.05) upon changing posture from the supine to the upright position. Ejection fraction (F = 33, P < 0.01), end-diastolic volume (F = 9, P < 0.05) and end-systolic volume (F = 10, P < 0.05) were significantly different between the two groups. In group 1, stroke volume, cardiac output and vascular peripheral resistance decreased from period A to period B (all P < 0.001). In group 2, no changes in stroke volume, cardiac output and vascular peripheral resistance were observed from period A to period B. All parameters were similar in the two groups during the periods A and C. Upon changing posture from the supine to the upright position, patients with Parkinson's disease and postural hypotension showed marked changes in parameters of LV function induced by vascular abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Electrocardiography, Ambulatory; Erythrocytes; Female; Gated Blood-Pool Imaging; Heart; Hemodynamics; Humans; Hypotension, Orthostatic; Male; Middle Aged; Monitoring, Ambulatory; Parkinson Disease; Radionuclide Ventriculography; Sodium Pertechnetate Tc 99m; Ventricular Function, Left

Patients with Parkinson's disease often experience dysphagia, in which case food seems to be blocked in the throat. The patient must swallow over and over to get it down. A radionuclide solid phase esophageal motility study was conducted to evaluate esophageal function of patients with Parkinson's disease. Twenty-seven patients and 27 age-matched normal volunteers were studied. Each subject was placed in the supine position above a gamma camera linked to a computer and was given a 4 mL bolus of solid gelatin containing 75 MBq Tc-99m pertechnetate. Data were acquired in the list mode. A computer routine was used to calculate the total mean transit time, the residual fraction after the first swallow, and the retrograde index. The preliminary results suggest: 1) patients with Parkinson's disease display significantly slowed transit time when compared with normal age-matched controls, and 2) dysphagia of Parkinson's disease may improve with medication. A solid phase esophageal motility study may be used as a monitor of dysphagia in patients with Parkinson's disease in our future studies.

Topics: Aged; Deglutition Disorders; Esophagus; Female; Gastrointestinal Transit; Humans; Male; Parkinson Disease; Peristalsis; Radionuclide Imaging; Sodium Pertechnetate Tc 99m