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BACKGROUND AND PURPOSE: There is sufficient evidence to support vitamin D's noncalcemic effects and the role of vitamin D deficiency in the development of a wide range of neurological disorders. This study aimed to evaluate whether serum 25(OH)D and 1,25(OH) 2 D could be used as biomarkers to differentiate between healthy subjects (HS), multiple system atrophy (MSA) and Parkinson's disease (PD) patients of both genders. METHODS: A total of 107 subjects were included in this study, divided into three groups: 1- HS (n = 61), 2- MSA patients (n = 19), and 3- PD patients (n = 27). The patients were assessed using UMSARS II, UPDRS III, H&Y, MMSE and MoCA rating scales. The levels of 25(OH)D and 1,25(OH) 2 D in serum were determined using the radioimmunoassay technique. RESULTS: The levels of 25(OH)D and 1,25(OH) 2 D in HS were 26.85 +/- 7.62 ng/mL and 53.63 +/- 13.66 pg/mL respectively. 25(OH)D levels were lower in both MSA and PD by 61% and 50%, respectively (P = 0.0001 vs. HS). 1,25(OH) 2 D levels were lower in MSA by 29%(P = 0.001 vs HS). There was a correlation between 25(OH)D and 1,25(OH) 2 D in MSA and PD, but not in HS. 1,25(OH) 2 D regressed with MMSE (ß = 0.476, P = 0.04, R 2 = 0.226) in MSA, and with UPDRS III (ß = -0.432, P = 0.024, R 2 = 0.187) and MoCA (ß = 0.582, P = 0.005,R 2 = 0.279) in PD. 25(OH)D displayed considerable differentiative strength between HS and MSA (Wald = 17.123, OR = 0.586, P = 0.0001; AUC = 0.982, sensitivity and Youden index = 0.882, P = 0.0001) and PD (Wald = 18.552, OR = 0.700, P = 0.0001; AUC = 0.943, sensitivity = 0.889, YI = 0.791, P = 0.0001). 1,25(OH) 2 D distinguished MSA from PD (Wald 16.178, OR = 1.117, P = 0.0001; AUC = 0.868, sensitivity = 0.926, Youden index =0.632, P = 0.0001). H&Y exhibited the highest sensitivity, AUC, and significant distinguishing power between MSA and PD. CONCLUSIONS: Serum 25(OH)D and 1,25(OH) 2 D could be useful biomarkers for MSA and PD. 25(OH)D and H&Y provided the highest sensitivity and group classification characteristics.
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ETHNOPHARMACOLOGICAL RELEVANCE: Japanese Angelica acutiloba root (Angelica root) is included in several Kampo medicines including Yokukansan (YKS). Angelica root and YKS are used for the treatment of a variety of psychological and neurodegenerative disorders. Development of safe and effective therapeutic agents against cerebrovascular disorders will improve the treatment of patients with dementia. AIM OF THE STUDY: The effect of Angelica root and YKS on ischemia-impaired memory has not yet been fully investigated. The present study investigated whether Angelica root is also involved in memory improving and neuroprotective effect of YKS in a model of cerebrovascular ischemia. MATERIALS AND METHODS: Male Wistar rats grouped into sham rats received saline, and other three groups subjected to repeated cerebral ischemia induced by 4-vessel occlusion (4-VO), received a 7-day oral administration of either saline, Angelica root or YKS. Memory was evaluated by eight-arm radial maze task. Acetylcholine release (ACh) in the dorsal hippocampus was investigated by microdialysis-HPLC. Apoptosis was determined by terminal deoxynucleotidyl transferase (TdT)-mediated fluorescein-deoxyuridine triphosphate (dUTP) nick-end labeling. RESULTS: Ischemia induced apoptosis, reduced release of ACh, and impaired the memory (increased error choices and decreased correct choices). Angelica root and YKS improved the memory deficits, upregulated the release of ACh and prevented 4-VO-induced hippocampal apoptosis. CONCLUSION: The dual ACh-increasing and neuroprotective effect of Angelica root could make it a promising therapeutic agent useful for the treatment of symptoms of cerebrovascular dementia. Angelica root could be one of the components contributing to the memory-improving and neuroprotective effects of YKS.
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Acetilcolina/metabolismo , Angelica , Apoptosis/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Hipocampo/efectos de los fármacos , Trastornos de la Memoria/prevención & control , Memoria/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Raíces de Plantas , Angelica/química , Animales , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatología , Isquemia Encefálica/psicología , Citoprotección , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/aislamiento & purificación , Hipocampo/metabolismo , Hipocampo/fisiopatología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/fisiopatología , Trastornos de la Memoria/psicología , Fármacos Neuroprotectores/aislamiento & purificación , Fitoterapia , Raíces de Plantas/química , Plantas Medicinales , Ratas Wistar , Regulación hacia ArribaRESUMEN
PURPOSE: In this study, gap junction expression and the effects of estrogen deficiency and gap junction inhibitors were investigated in overactive bladder models which were created by bladder outlet obstruction. METHODS: In our study, we created four groups as control, ovariectomy, bladder outlet obstruction (BOO), and ovariectomy + BOO. We investigated the effects of oxybutynin and 18-alpha glycyrrhetinic acid (18-α-GA) which is a gap junction blocker on isolated detrusor strips. Western blot method was used to measure the level of connexin-43 in detrusor. RESULTS: Bladder weights were significantly increased in the BOO and ovariectomy + BOO groups (p < 0.05). There was no statistically significant difference in the maximal contraction responses to carbachol between ovariectomy and control groups. In BOO and ovariectomy + BOO groups, contractile responses were significantly prominent with higher doses of carbachol. Oxybutynin-induced relaxant responses of BOO and ovariectomy + BOO groups were significantly higher than control group (p < 0.05). The relaxation effect of 18-a-GA was more effective in the obstruction groups. Among those two groups, the relaxation observed in BOO group was higher than ovariectomy + BOO group in higher doses of 18-a-GA. Connexin-43 expression was increased in BOO group compared with the control group (p = 0.006). Ovariectomy did not change connexin-43 expression alone; however, when combined with BOO, connexin-43 expression decreased significantly (p = 0.023). CONCLUSIONS: Ovariectomy had no effect on the gap junctions in the bladder and bladder overactivity alone. Therefore, obstruction is the main factor that increases the amount of gap junctions, and gap junction blockers are thus more effective in obstruction. However, ovariectomy was shown to decrease the expression of gap junctions and relaxation effect of gap junction blockers, when combined with BOO.
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Uniones Comunicantes/efectos de los fármacos , Ácidos Mandélicos/farmacología , Antagonistas Muscarínicos/farmacología , Ovariectomía , Obstrucción del Cuello de la Vejiga Urinaria/tratamiento farmacológico , Análisis de Varianza , Animales , Western Blotting , Carbacol/farmacología , Conexina 43/metabolismo , Modelos Animales de Enfermedad , Femenino , Uniones Comunicantes/metabolismo , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Sensibilidad y Especificidad , Obstrucción del Cuello de la Vejiga Urinaria/metabolismo , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/metabolismoRESUMEN
The effects of Toki-shakuyaku-san (TSS) ingredients on acetylcholine (ACh) release in the dorsal hippocampus (DH) were investigated in intact and twice-repeated ischemic rats using in vivo microdialysis-HPLC. Moreover, the effect of TSS on blood flow was investigated in intact rats using laser Doppler flowmetry. TSS at 300 mg/kg p.o. increased ACh and blood flow after 40 min in intact rats. TSS also increased ACh in ischemic rats but to a lesser extent than in intact rats. These results could suggest that TSS-increased ACh and blood flow in DH may contribute in the cognition improving property of TSS.