Comparison of the Effect of Glutamate; Oxyferriscorbone and Deprenyl on Parkinsonian Syndrome

Background: Patients with Parkinson's disease (PD) show a dramatic increase in their brain iron content has suggested the role of iron in degeneration of dopaminergic nigrostriatal neurons in PD. Several studies have described the association of high dietary iron and PD. However; the role of iron the pathogenesis of PD is still hotly debated. Objective: The purpose of this study was to investigate the effects of L-glutamate; oxyferriscorbone (OFC) and L-Deprenyl on parkinsonian syndrome (PS) in rats. Methods: This study was performed on 244 male non-strain rats (250-270g;-10 wk old). By intranigral bilateral administration of 1-Methyl-4-phenylpyridinium ion (MPP+) (10?g/2?/l into each side) and 6-hydroxydopamine (6-OHDA) (12?g/3?l; Sigma; into each side ) in rats was induced the dopamine deficient model of PS (DDPS) and the cholinergic model (ChPS) in rats produced by intracaudate injection of acetylcholine (5?g/2?l each side ) with neostigmine (1?g/1?l each side). These models were then used to investigate the effects of L-glutamate; OFC and L-Deprenyl on PS and the electric activity (EA) of the sensorimotor cortex; caudate nuclei; ventrolateral nuclei of the thalami; and substantia nigra in rats. Results: Intracaudate injection of L-glutamate (100?g/3?l; into each side) enhanced bradykinesia; rigidity and produced a weak tremor in the DDPS. This effect was more pronounced in ageing (12 months) rats and in some of them; we observed orofacial dyskinesia. In the ChPS; L-glutamate enhanced tremor and bradykinesia. The single and repeated injection of OFC (5; 7; 5; 15 and 20 mg/rat; intraperitioneally; i.p.) did not produce a statistically significant change of PS in both models. L-deprenyl (5; 10 and 20 mg/kg; i.p.) dose-dependently reduced bradykinesia and rigidity in the DDPS; whereas increased tremor and failed to decrease bradykinesia and rigidity in the ChPS. Conclusion: This study indicates that glutamate aggravates PS in both models. OFC does not have any effect on PS. Deprenyl has antiparkinsonian effect in the DDPS; but not in the ChPS

Disorders of the Basal Ganglia at the University Teaching Hospital; Lusaka

Objective: To determine the frequency of movement disorders among adult ethnic Zambians referred to the University Teaching Hospital (UTH) Lusaka; Zambia and logged as patients with primary neurological disorders. Background: The Human Genome Project data showed that humans are identical across 99.9of their genome. There is considerable evidence that despite being genetically identical; race and ethnicity appears to be an important factor in the prevalence and clinical characteristics of many; if not most; disorders. Literature review clearly shows that ethnicity has an essential role in the phenotypic expression of many movement disorders and their prevalence appears to be lowest amongst Africans. Patients and setting: Patients attending the neurology clinic and admitted to the UTH with various neurological disorders for 5 years (January 1999-January 2004) were analysed. We evaluated patients whose symptoms met the appropriate diagnostic criteria for movement disorders and experienced symptoms at least for three days. Results: Records were available for 4654 patients with various neurological disorders attending neurological clinic. Of the total number of patients seen; 163 (3.5) satisfied the criteria for movement disorders. The most frequent syndromes of the basal ganglia were: Parkinson's disease (31); tremor (24); chorea (20); and dystonia (16.5). Myoclonus; tic; tardive dyskinesia; and other movement disorders (8.5) were rare in adult Zambian patients. In 25 patients (11.3) akinetic-rigid syndromes and hyperkinetic movement disorders were manifestations of HIV/AIDS. Conclusions: Among patients referred for neurological services at Zambia's tertiary care teaching facility; movement disorders are relatively rare. Our study may seem to suggest that Parkinson's disease is one of the commonest movement disorders though further studies are needed to explore the role of genetics and ethnicity in the prevalence of these disorders. The presence of HIV/AIDS and its contribution to movement disorders needs to be studied further

Knowledge, attitudes, behaviors, and practices regarding epilepsy among Zambian clerics.

BACKGROUND: Epilepsy carries a high burden of social morbidity. An understanding of who propagates stigma and the determinants of stigmatizing attitudes is needed to develop effective interventions. Clerics represent an especially influential social group in Africa. Therefore, we conducted a survey of the knowledge, attitudes, behavior, and practices of Zambian clerics with respect to epilepsy. METHODS: We studied clerics in one large rural region as well as in the capital city. The rural survey was conducted door-to-door. In the urban areas, central administration for multiple denominations assisted in survey delivery. The survey, adapted from previously published instruments, included cleric-specific questions and demographic data. Composite scores for knowledge and tolerance were developed. Determinants of higher knowledge and tolerance were assessed. RESULTS: Almost all Zambian clerics know someone with epilepsy and have witnessed a seizure. More than 40% report having a family member with epilepsy. Unfortunately, this familiarity is not associated with more knowledge or tolerance for the condition. Younger clerics, urban dwellers, those with fewer children, and those with more years of formal education were significantly more tolerant. More knowledgeable clerics are more likely to recommend that a person with epilepsy seek care from a physician rather than a traditional healer. Formal education was the most important factor in determining tolerance toward epilepsy. CONCLUSIONS: Zambian clerics are very familiar with epilepsy, yet have relatively little knowledge of the etiology. Many view traditional healers as the appropriate care provider for epilepsy. To decrease stigma and improve the quality of advice offered by clerics to their congregations, educational programs focusing on the biomedical nature of the disorder are needed, particularly in rural regions.

Study of familial Parkinson's disease in Russia, Uzbekistan, and Zambia.

OBJECTIVE: The aims of this study were (A) to determine inheritance patterns of familial Parkinson's disease in three different geographical areas (Russia, Uzbekistan, and Zambia); (B) compare clinical characteristics of familial with sporadic Parkinson's disease; and (C) assess whether there were ethnic differences in clinical manifestations of the disease. METHODS: Fifty two index cases of familial Parkinson's disease in Moscow, 55 in Tashkent, and 27 in Lusaka were selected on the basis of the typical clinical features of Parkinson's disease with a familial history. The sex ratio, transmission patterns, and segregation ratio were determined by pedigree analysis. RESULTS: Familial Parkinson's disease was found in all three countries (30 families in Russia, 12 in Uzbekistan, and seven in Zambia), and appeared more common in Russia. Both autosomal dominant and autosomal recessive patterns of inheritance were seen, but autosomal dominance was more common in all countries. CONCLUSIONS: In all three countries men have a higher risk of developing Parkinson's disease than women and there are ethnic differences in clinical manifestations of the disease. The onset of both familial and sporadic Parkinson's disease in Zambian patients occurs at a younger age and is associated with slow progression and a benign course, and generally responds well to levodopa treatment.

[Phospholipid spectrum in target organs in chronic stress]. / Spektr fosfolipidov v organakhmisheniiakh pri khronicheskom stress.

The phospholipid composition of the viscera, such as the heart, liver, the fundal part of the stomach, arterial wall and the truncal part of the brain, was studied in rats exposed to chronic stress. The changes in the visceral phospholipid spectrum during chronic stress were found to be phasic, which appeared as significant increases in parameters under study within the first fortnight and their drastic drop at month 2 of stress. The time course of changes occurring in the phospholipid spectrum was held to be associated with adaptive and maladaptive phases of chronic stress. Unlike the viscera, the brain and erythrocytes showed no substantial changes in the major phospholipid fractions during chronic stress. The findings are regarded as evidence for the change-over of carbohydrate oxidation to lipid oxidation in the viscera during chronic stress, but not in the brain and erythrocytes.

[Serotonin antibodies and their possible role in parkinsonism]. / Antitela k serotoninu i ikh vozmozhnaia rol' pri parkinsonizme.

Serotonin antibodies (SAb) were found in the blood sera of middle-aged and elderly parkinsonian patients. The incidence of Sab in young and middle-aged healthy subjects was less, but increasing with age. Injected into the rabbit caudate nuclei, Sab suppressed the main pathogenetic mechanism of parkinsonian syndrome, the generator of pathologically enhanced excitation (GPEE) and parkinsonian symptoms induced by the MPP injection into substantia nigra. The intracaudate injection of serotonin enhanced GPEE activity and parkinsonian syndrome. The role of serotoninergic system and Sab in parkinsonism is discussed.

[Role of the striatal serotoninergic apparatus in Parkinsonian syndrome]. / Uchastie serotoninergicheskogo apparata striatuma v parkinsonicheskom sindrome.

Injected into the rat caudate nuclei (CN) serotonin promotes the generator of pathologically enhanced excitation (GPEE) in CN and parkinsonian symptoms, induced by MPP+ injection into substantia nigra. Serotonin antibody injected in CN decreases the GPEE activity and partly suppresses the parkinsonian symptoms. The role of serotoninergic system in parkinsonism is discussed.

[The effect of bromocryptin on rotational activity in rats]. / Vliianie bromokriptina na rotatsionnuiu aktivnost' krys.

The experiments were made in rats with unilateral lesion to the nigrostriatal tract, which was induced by the highly active dopaminergic neurotoxin 1-methyl-4-phenyl-pyridinium. The rotational activity of rats was evaluated after intragastric and subcutaneous bromocryptine given in a single dose of 10 mg/kg and 25 mg/kg one, two, three and four times. The highest effect of the drug was seen when it was used in the maximum dose of 25 mg/kg, but when the agent is repeatedly given in the above dose, it failed to enhance the rotational activity of rats. The findings may provide evidence for possibilities of increasing the doses of bromocryptine in practical medicine, and for designing the injectable dosage form of the drug.

[The characteristics of a parkinsonian syndrome induced in an experiment by a deficiency of nigrostriatal dopamine and by stimulation of the cholinergic neurons of the caudate nucleus]. / Osobennosti parkinsonicheskogo sindroma, vyzvannogo v éksperimente defitsitom nigrostriarnogo dofamina i stimuliatsiei kholinergicheskikh neironov khvostatykh iader.

An experimental parkinsonian syndrome (PS) was induced by systemic administration of MPTP or oxotremorine, by intranigral administration of MPP+ or injection of acetyl choline and proserine into the rostral part of both caudate nuclei. The development of extrapyramidal disorders was studied simultaneously with EEG recording. The electric activity (EA) was recorded in the sensorimotor cortex, caudate nuclei, ventrolateral nuclei of the thalami, substantia nigra and globus pallidus. Tremor, oligokinesia and rigidity were characterized by the appearance of paroxysmal activity on EA with high amplitude of slow and rapid waves. The data obtained allow us to conclude that PS neuropathophysiological basis is the formation of the generator of pathologically enhanced excitation (GPEE) in the caudate nuclei. It was found that akinesia-rigidity syndromes were observed in the rats with both MPTP and MPP(+)-induced PS. Tremor was observed after administration of oxotremorine or acetyl choline with proserine more often than after treatment with MPTP or MPP+. Some peculiarities of the GPEE activity in these forms of PS were observed. Also, there is dissociation in effects of antiparkinsonian drugs in different forms of PS.

[Effects of difenin on experimental parkinsonian syndrome]. / Vliianie difenina na éksperimental'nyi parkinsonicheskii sindrom.

The aim of this study was to investigate the effect of difenin on parkinsonian syndrome and the generator of pathologically enhanced excitation (GPEE) in the caudata nuclei (CN). Repeated i. p. administration of MPTP in 12 month rats induced oligokinesis and rigidity followed by the high amplitude slow and rapid waves in the CN and in sensorimotor cortex (SC). The changes of the electrical activity in the CN were more prominent then in SC. I.p. injection of difenin (20 mg/kg) resulted in an increase of motor activity and decrease of rigidity in rats. The reduction of extrapyramidal symptoms were correlated with at the inhibition of GPEE in the CN. These data suggest that difenin can be a part of the complex pathogenetic therapy of parkinsonian syndrome.

[Effects of substance P on experimental parkinsonian syndrome]. / Vliianie substantsii P na éksperimental'nyi parkinsonicheskii sindrom.

The aim of this study was to investigate the effect of substance P (SP) on parkinsonian syndrome and the generator of pathologically enhanced excitation (GPEE) in the caudate nuclei (CN). Repeated i. p. administration of MPTP in 12 month rats induced oligokinesia and rigidity followed by the high amplitude slow and rapid waves in both CN. The changes of electrical activity in CN were more prominent than in the sensorimotor cortex. The bilateral intracaudate injection of SP (5 micrograms) resulted in an increase in motor activity and almost completely abolished the rigidity. The reduction of extrapyramidal symptoms was considered as a result of the inhibition of GPEE. The changes of the SP balance in nigro-striatal system was suggested to be one of the pathogenetic links of parkinsonian syndrome.

[Parkinson syndrome after administration of acetylcholine into the caudate nuclei]. / Sindrom Parkinsona posle vvedeniia atsetilkholina v khvostatye iadra.

Rats with the Parkinsonian syndrome induced by administration of acetyl choline and proserine into the rostral part of both caudate nuclei manifest an increased electrical activity (EA) in this part. Tremor, oligokinesia and rigidity are characterized by the appearance of paroxysmal EA with high amplitude of slow and rapid waves. The data obtained allow to conclude that neuropathophysiological basis of the Parkinsonian syndrome is the formation of the generator of pathologically enhanced excitation (GPEE) in the caudate nuclei. Some peculiarities of the GPEE activity in tremor and akinetic rigidity syndromes were observed. Intrarostral administration of dopamine or intraperitoneal administration of cyclodol resulted in the inhibition of GPEE and disappearance of clinical manifestations of Parkinsonian syndrome.

[Clinico-electroencephalographic indices of the parkinsonian syndrome induced by MPP+ in rats]. / Kliniko-élektroéntsefalograficheskie pokazateli parkinsonicheskogo sindroma, vyzvannogo MFP+ u krys.

The bilateral intranigral injection of 1-methyl-4-phenyl-pyridinium ion (MPP+) (10 g) produced significant oligokinesia, rigidity and weak tremor in rats. The extrapyramidal disturbances manifest a high-amplitude paroxysmal activity (PA) in the structures studied. It was found that the Pa was remarkable and more stable in the caudata nucleus than in other brain structures. It is PA that gives us the real basis to conclude the formation of the generator of pathologically enhanced excitation (GPEE) in the caudata nuclei. The analysis of PA dynamics revealed that the formation of the GPEE in the caudata nuclei correlated with development of parkinsonian syndrome (PS).

[EEG changes and symptomatic parkinsonism after intracaudate administration of dopamine antibodies]. / Izmenenie EEG i iavleniia parkinsonizma pri intrakaudatnom vvedenii antitel k dofaminu.

Intracaudate bilateral injection of the dopamine antibodies caused the formation of the generator of pathologically enhanced excitation in caudate nuclei. All the rats exhibited the oligokinesia, rigidity and head tremor were observed in most animals. These abnormalities could be observed during 24 hours. The possible role of dopamine antibodies in parkinsonism pathogenesis is discussed.

[Lipid peroxidation in the caudate nuclei in experimental parkinsonian syndrome]. / Perekisnoe okislenie lipidov v kvostatykh iadrakh pri éksperimental'nom parkinsonicheskom sindrome.

Lipid peroxidation was investigated in adult (8-10 months of age) rat striatum with Parkinsonian syndrome induced by MPTP and its metabolite MPP+. MPTP 20 mg/kg i.p. 4 doses) produced a slight enhancement of lipid peroxidation and significant increase when MPP+ (0.04 mg/kg) was injected into the substantia nigra.

[Experimental parkinsonian syndrome in rats induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine]. / Eksperimental'nyi parkinsonicheskii sindrom u krys, vyzvannyi 1-metil-4-fenil-1,2,3,6-tetragidropiridinom.

Systemic administration of high doses of MPTP caused transient bradykinesia, "freezing" episodes, head tremors, hunching of the back and peripheral autonomic effects. Neurological syndrome was clearly dose-dependent. It has been established that Parkinson's syndrome is caused by high-amplitude paroxysmal discharges in the nucleus caudatis. It is concluded that the nucleus caudatis plays the role of a pathological determinant structure in the development of Parkinson's syndrome induced by MPTP.