Evaluation of gastric emptying in familial and sporadic Parkinson disease

ObjectiveTo assess for the presence of gastric dysmotility in familial and sporadic Parkinson disease (PD).Methods10 subjects with familial Parkinson disease (fPD), 35 subjects with sporadic Parkinson disease (sPD), and 15 controls, all from academic tertiary care movement disorders centers, were studied. fPD was defined as the presence of at least 2 affected individuals within 2–3 consecutive generations in a family. Molecular genetic analysis has not revealed, thus far, any known genomic abnormality in these families. Gastric emptying was assessed by dynamic abdominal scintigraphy over 92 min following ingestion of a solid meal containing 99mTc-labeled colloid of 40 MBq activity. The main outcome measures were gastric emptying half-time and radiotracer activity over the gastric area at 46 and at 92 min.ResultsGastric emptying time was delayed in 60% of subjects with PD. In comparison to mean t_1/2 of 38 ± 7 min in controls, mean t_1/2 was 58 ± 25 min in fPD (p = 0.02) and 46 ± 25 min in sPD (p = 0.10). Both fPD and sPD groups included subjects with delayed gastric emptying at an early stage of disease.ConclusionsPatients with fPD showed significantly delayed gastric emptying in comparison to normal age-matched individuals. Further studies of gastrointestinal dysfunction in PD, particularly fPD, are warranted.     

Synthesis and Structure Elucidation of 5-Aminomethinimino-3-methyl-4-isoxazolecarboxylic Acid Phenylamides and Their Immunological Activity

A series of 5-aminomethinimino-3-methyl-4-isoxazolecarboxylic acid phenylamides 4 has been prepared by condensation of 5-amino-3-methyl-4-isoxazolecarboxylic acid phenylamides 1 with trichloroacetic aldehyde. Alcoholysis of trichloro derivatives 2 gave 5-alkoxymethine derivatives 3 which, on reaction with an appropriate amine, formed the corresponding compounds 4 . The compounds obtained were evaluated for their immunological activity. The properties of three compounds, described in this report, permitted inhibition of the immune response in all possible ways: diminishing both types of immune response ( 4d ), humoral immune response ( 4a ), or cellular immune response ( 4c ). Preparation 4d is comparable in its effectiveness to CsA, so it may be potentially used as an agent for prolongation of the function of transplanted organs. Two other compounds may potentially be used in cases where only one type the immune response is required for combating pathogen invasion.     

Tetanus incidence and immunity in Poland

The level of tetanus antibody was determined with the passive hemagglutination method in 503 sera of 10 to 90-year-old persons. Immunity to tetanus was age-dependent: the percentage of immune persons amounted to 90% –100% in persons below 40 years and then declined to 70% and 60% in persons in the 40 – 50 and above 50 year-old groups, respectively. Males above 30 years are better immunized than females. The comparison of the results of the present study with results of several periodic surveys performed in the last 27 years showed gradually increasing immunity level in all age groups. The findings are in agreement with age-dependent incidence of tetanus, which has become now, in Poland, a disease primarily of older people.     

Control of pertussis in the world.

Available data indicate that pertussis remains an important disease during infancy and childhood, particularly among those who are inadequately immunized. Over the past 15 years, successful immunization programmes have been implemented in most countries in the world. Some problems have arisen in the industrialized world where pertussis had been well controlled previously. The underlying causes of these problems are apathy and complacency on the part of physicians and parents, negative attitudes to immunization spread by anti-immunization pressure groups and litigation over liability for alleged vaccine-related injures. In developing countries, immunization coverage with primary series of three doses of DPT vaccine in infants exceeds 80%, but there are considerable differences in coverage rates between regions and between and within countries. Failures to reach and maintain high immunization coverage in developing countries are caused by multiple factors including weak management of immunization services, missing opportunities to immunize eligible children and ineffective information and motivation of mothers to return to complete the immunization series. To effectively control pertussis in the world, all countries should use available pertussis vaccines in immunization programmes for children. Since acellular pertussis vaccines are not generally available, the widespread use of DPT vaccine containing the whole-cell pertussis component should be continued. All efforts should be directed to increase or maintain high immunization coverage with DPT immunization at the level of at least 90% in all districts. Surveillance of pertussis morbidity should be strengthened in all countries and ideally, pertussis should be a reportable disease. More information on the present epidemiological pattern of pertussis, especially age distribution of pertussis cases in developing countries, is needed to develop the policy of booster doses of DPT vaccine in children > 1 year.     

Frontotemporal dementia and parkinsonism linked to chromosome 17 with the N279K tau mutation

We present a case of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) harboring the N279K mutation in the MAPT gene from the family known as pallido‐ponto‐nigral degeneration (PPND). This 49‐year‐old man was followed for 17 years. He presented at age 41 years with left leg stiffness and en‐bloc turning. During the course of his illness he developed a constellation of symptoms including parkinsonism, pyramidal signs, vertical gaze palsy, dysphagia, dystonia, personality and cognitive dysfunction, weight loss and mutism. Gross neuropathological examination showed mild atrophy of the cerebral cortex, hippocampal formation, amygdala, thalamus, subthalamic nucleus and depigmentation of the substantia nigra. Microscopy revealed neuronal loss and gliosis in the same regions. Tau immunohistochemistry showed pretangles, numerous threads, grain‐like structures and oligodendroglial tau‐positive inclusions (“coiled bodies”). In the spinal cord the tau pathology was more abundant in gray than white matter. Pretangles and threads were present in the anterior and, to a lesser extent, in the posterior horns. FTDP‐17 should be suspected in patients with a history of familial parkinsonism combined with behavioral and cognitive changes, onset before age 65 years and an aggressive clinical course.     

Brain uptake of radiolabeled N‐oleoyl‐dopamine in the rat

N‐acyl‐dopamines are a novel class of biologically active lipids that have recently been identified in the brain and have the potential to interact with neural signaling pathways. This study seeks to determine the ability of N‐oleoyl‐dopamine, a synthetic amide of oleic acid and dopamine, to cross the blood brain barrier. We determined the tissue content of radioactivity in selected brain regions, in a short‐run study design, following injections of [³H]N‐oleoyl‐dopamine (0.4 µCi) into the internal carotid artery in the rat. These results were compared with intracarotid injections of [³H]dopamine and with intravenous injections of both radiolabeled compounds. The level of radioactivity was determined using liquid scintillation and was expressed as the percentage of its total dose injected per gram of tissue. We found that the 15‐min brain uptake of radioactivity, with no distinct regional variations, amounted to about 6% following the intracarotid [³H]N‐oleoyl‐dopamine, which was a significant 3–4‐fold increase over that following similar administration of [³H]dopamine. Intravenous injections of [³H]N‐oleoyl‐dopamine gave a much smaller yield of radioactivity in brain tissue samples which was still severalfold greater than that for intravenous [³H]dopamine. Qualitative thin‐layered chromatography screening showed the presence of unchanged N‐oleoyl‐dopamine in the brain following injections. We conclude that N‐oleoyl‐dopamine has an appreciable ability to cross the blood‐brain barrier, which contrasts the limited transfer of dopamine alone. N‐oleoyl‐dopamine might exert physiological effects due to its known affinity for the central vanilloid receptors or to better satisfying the brain tissue demand for dopamine. The study suggests a potential pharmacological role for N‐oleoyl‐dopamine delivered exogenously in helping regulate the brain function. Drug Dev. Res. 60:217–224, 2003. © 2003 Wiley‐Liss, Inc.     

Increase in levels of total free fatty acids in rat brain regions following 3-nitropropionic acid administration

Acute exposure to a neurotoxin, 3-nitropropionic acid (3-NPA), in rats results in an increase in total free fatty acid (FFA) concentration in selective brain regions. We investigated the effect of 3-NPA administration on the cerebral concentrations of FFA used as a marker of oxidative stress. Rats (n=3/group) were dosed subcutaneously (s.c.) either with a vehicle (phosphate buffer) or 3-NPA in phosphate buffer at 30 mg/kg body weight. Animals were sacrificed after 1, 2, 3, and 6 h of injection. Brains were then dissected into frontal cortex (FC), caudate nucleus (CN), and hippocampus (HIP). The concentration of total FFA increased from 130 to 300% within 1–2 h after 3-NPA injection in all brain regions when compared with the baseline level obtained from the control rats and taken as 100%. In CN, FFA returned to the baseline level within 3 h of treatment. However, in FC and HIP the concentration of FFA remained significantly elevated above the baseline until 6 h. The released FFA provide a substrate for free radicals formation. The results of this study suggest a role of oxidative stress in the mechanism of 3-NPA toxicity.     

Application of the Minnesota Code in evaluating electrocardiographic features of ischemic heart disease in patients exposed to carbon disulphide

Summary We examined 81 men exposed for a long time to carbon disulphide (CS₂) and tested the possible electrocardiographic (ECG) changes of ischemic heart disease (I.H.D.). The subjects were examined twice in two years. In order to make the ECG evaluation more objective, the Minnesota Code was applied. Two obligatory ECG examinations and only one submaximal effort test were carried out. For comparative evaluation, the control group was examined once. We proved that, in spite of the accepted opinion concerning the atheromatous action of CS₂, this compound does not cause ECG symptoms of I.H.D. in a higher percentage of exposed persons. It also does not cause any significant increase in I.H.D. symptoms in dynamic ECG observations.