RESUMEN
BACKGROUND: Parkinson's disease (PD), the most prevalent type of Parkinsonism, is a progressive neurological condition characterized by a range of motor and non-motor symptoms. The complicated etiology of PD is thought to involve a summation of aging, genetic predisposition, and environmental variables. However, the α-synuclein protein plays a significant role in the disease's pathophysiology. MATERIALS AND METHODS: The UAS-α-Syn and Ddc-Gal4 strains were crossed to produce offspring referred to as PD flies. The entire population of flies was divided into five groups, each having about 100 flies and five replicates. The control group (w1118) and the PD group not receiving treatment were exposed to lauric acid (LA)/levodopa (LD)-free diet, while the PD groups that received treatments were fed with either a 250 mg/kg LA diet, a 250 mg/kg LD diet, or a combination of the two for 21 days. Longevity, geotaxis, and olfactory assays were performed in addition to other biochemical tests. RESULTS: As a result of the overexpression of α-synuclein, the locomotive capacity, lifespan, and antioxidant status were all significantly (p < .05) reduced, and the apoptotic and neuroinflammatory activities were increased. Nevertheless, the majority of the treated flies improved significantly (p < .05). CONCLUSION: LA, whether combined with LD or not, elicited a significant response in α-synuclein/dopa decarboxylase genetically modified Drosophila melanogaster Parkinsonism models.
Asunto(s)
Apoptosis , Modelos Animales de Enfermedad , Drosophila melanogaster , Ácidos Láuricos , Levodopa , Trastornos Parkinsonianos , Animales , Drosophila melanogaster/efectos de los fármacos , Ácidos Láuricos/farmacología , Ácidos Láuricos/administración & dosificación , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/metabolismo , Levodopa/farmacología , Levodopa/administración & dosificación , Apoptosis/efectos de los fármacos , alfa-Sinucleína/metabolismo , Animales Modificados Genéticamente , Estrés Oxidativo/efectos de los fármacos , Longevidad/efectos de los fármacos , MasculinoRESUMEN
Parkinson's disease (PD), the most prevalent type of parkinsonism, is a progressive neurodegenerative condition marked by several non-motor and motor symptoms. PD is thought to have a complex aetiology that includes a combination of age, genetic predisposition, and environmental factors. Increased expression of α-synuclein (α-Syn) protein is central to the evolvement of neuropathology in this devastating disorder, but the potential of ribose-cysteine and levodopa in abating pathophysiologic changes in PD model is unknown. Crosses were set up between flies conditionally expressing a pathological variant of human α-Syn (UAS-α-Syn) and those expressing GAL4 in neurons (elav-GAL4) to generate offspring referred to as PD flies. Flies were randomly assigned to five groups (n = 40) from the total population of flies, with each group having five replicates. Groups of PD flies were treated with either 500 mg/kg ribose-cysteine diet, 250 mg/kg levodopa diet, or a combination of the two compounds for 21 days, whereas the control group (w1118) and the PD group were exposed to a diet without ribose-cysteine or levodopa. In addition to various biochemical and neurochemical assays, longevity, larval motility, and gravitaxis assays were carried out. Locomotive capability, lifespan, fecundity, antioxidant state, and neurotransmitter systems were all significantly (p < 0.05) compromised by overexpression of α-Syn. However, flies treated both ribose cysteine and levodopa showed an overall marked improvement in motor functions, lifespan, fecundity, antioxidant status, and neurotransmitter system functions. In conclusion, ribose-cysteine and levodopa, both singly and in combination, potentiated a therapeutic effect on alpha-synuclein transgenic Drosophila melanogaster models of Parkinsonism.
Asunto(s)
Antioxidantes , Enfermedad de Parkinson , Animales , Humanos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Antioxidantes/administración & dosificación , Antioxidantes/metabolismo , Cisteína/metabolismo , Modelos Animales de Enfermedad , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Levodopa/farmacología , Levodopa/metabolismo , Neurotransmisores , Oxidación-Reducción , Enfermedad de Parkinson/tratamiento farmacológico , Ribosa , Animales Modificados Genéticamente , Distribución AleatoriaRESUMEN
BACKGROUND AND AIMS: Intravenous immunoglobulin (IVIg) has a rapid clinical effect which cannot be explained by remyelination during each treatment cycle in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This study aimed to investigate axonal membrane properties during the IVIg treatment cycle and their potential correlation with clinically relevant functional measurements. METHODS: Motor nerve excitability testing (NET) of the median nerve was performed before and 4 and 18 days after initiation of an IVIg treatment cycle in 13 treatment-naïve (early) CIDP patients and 24 CIDP patients with long term (late) IVIg treatment, 12 CIDP patients treated with subcutaneous immunoglobulin (SCIg) and 55 healthy controls. Clinical function was measured extensively using the Six Spot Step test, 10-Meter Walk test, 9-Hole Peg test, grip strength, MRC sum score, Overall Neuropathy Limitations Score and Patient Global Impression of Change. RESULTS: Superexcitability and S2 accommodation decreased significantly in the early treatment group from baseline to day 4 and returned to baseline levels at day 18, suggesting temporary depolarization of the axonal membrane. A similar trend was observed for the late IVIg group. Substantial clinical improvement was observed in both early and late IVIg groups during the entire treatment cycle. No statistically significant correlation was found between clinical and NET changes. No change was found in NET or clinical function in the SCIg group or controls. INTERPRETATION: NET suggested temporary depolarization of the axonal membrane during IVIg treatment in treatment naïve CIDP patients. The relation to clinical improvement, however, remains speculative.
Asunto(s)
Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Humanos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Inmunoglobulinas Intravenosas/uso terapéutico , Fuerza de la Mano , Inmunización PasivaRESUMEN
BACKGROUND: The occurrence of endocrine diseases in people who are infected with HIV is traditionally thought to occur in the setting of AIDS with opportunistic infections and malignancies. However, recent studies find the correlation between hypocortisolism and stage of HIV (CD4 count and WHO clinical stage) inconsistent. METHODS: This descriptive cross-sectional study included three hundred and fifty (350) consecutive patients with HIV infection. They were interviewed, and subsequently underwent laboratory evaluation for the detection of hypocortisolism. Blood samples for serum cortisol estimation were taken at baseline and at 30 minutes following the administration of 1µg of tetracosactrin (Synacthen). In addition, the patients had blood samples taken at 0 minutes (baseline) for CD4+ lymphocyte cell counts. RESULTS: At baseline, 108 (30.9%) participants had serum cortisol levels below 100 µg/L with a median value of 55.48 µg/L (11.36-99.96 µg/L), but only 57 (16.3%) study participants had stimulated serum cortisol levels below 180 µg/L with median of 118 µg/L (19.43-179.62). There was no significant difference in the occurrence of clinical features between participants with low and normal serum cortisol, nor WHO clinical stage, CD4 count and ART regimen. The occurrence of hypocortisolism was higher among participants who had been on ART for a longer period of time. CONCLUSION: There is a high prevalence of hypocortisolism among HIV patients by biochemical testing, especially those who have been on ARVs for a longer duration. Hypocortisolism cannot be predicted based on the participants' WHO clinical stage of disease, CD4 cell count, or the treatment regimen. FUNDING: Personal Funds.