ABSTRACT
BACKGROUND: Although stem cell transplantation has been successfully performed for cerebral palsy (CP) related to oxygen deprivation, clinical trials involving the use of stem cell transplantation for CP related to neonatal icterus have not been reported. The aim of this study was to evaluate the effectiveness of transplantation of autologous bone marrow mononuclear cell (BMMC) for improving gross motor function and muscle tone in children with CP related to neonatal icterus. METHODS: This open-label, uncontrolled clinical trial, which included 25 patients with CP related to neonatal icterus who had a Gross Motor Function Classification System (GMFCS) score between level II and level V, was conducted between July 2014 and July 2017 at Vinmec International Hospital (Vietnam). BMMC were harvested from the patients' iliac crests. Two procedures involving BMMC transplantation via the intrathecal route were performed: the first transplantation was performed at baseline, and the second transplantation was performed 6 months after the first transplantation. Gross motor function and muscle tone were measured at three time points (baseline, 6 months, and 12 months) using the Gross Motor Function Measure (GMFM) and the Modified Ashworth Scale. RESULTS: In this trial, we observed significant improvement in gross motor function and a significant decrease in muscle tone values. Total score on the 88-item GMFM (GMFM-88), scores on each GMFM-88 domain, and the 66-item GMFM (GMFM-66) percentile were significantly enhanced at 6 months and 12 months after the first transplantation compared with the corresponding baseline measurements (p-values < 0.05). In addition, a significant reduction was observed in muscle tone score after the transplantations (p-value < 0.05). CONCLUSION: Autologous BMMC transplantation can improve gross motor function and muscle tone in children with CP related to neonatal icterus. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03123562 . Retrospectively registered on December 26, 2017.
Subject(s)
Bone Marrow Transplantation/methods , Cerebral Palsy/therapy , Jaundice, Neonatal/complications , Leukocytes, Mononuclear/transplantation , Motor Activity , Muscle Hypotonia/therapy , Adolescent , Analysis of Variance , Autografts , Brain/diagnostic imaging , Cerebral Palsy/diagnostic imaging , Cerebral Palsy/etiology , Child , Child, Preschool , Female , Humans , Magnetic Resonance Imaging , Male , Muscle Spasticity , Severity of Illness IndexABSTRACT
A series of new angiotensin II receptor 1 antagonists were prepared. They displayed nanomolar affinity to AT1 receptor and could decrease blood pressure efficiently in spontaneously hypertensive rats. Among them, compounds 1b and 2b could reduce the blood pressure with more or equal potency compared to Losartan. So, compounds 1b and 2b could be considered as potential antihypertension drug candidates.
ABSTRACT
OBJECTIVE: To study the effect of tea polyphenols (TP) on c-Jun N-terminal kinase 1/2 (JNK1/2) phosphorylation and cell apoptosis in brain tissues in rats with cardiac arrest (CA) following cardiopulmonary resuscitation (CPR). METHODS: Healthy male Sprague-Dawley (SD) rats were randomly divided into sham group (n = 6), CA group (n = 12), and TP group (n = 12). The rats in CA and TP groups were induced ventricular fibrillation (VF) via esophagus stimulation with alternating current. Five minutes after CA, CPR was performed. Once restoration of spontaneous circulation (ROSC) was gained, normal saline (NS) and TP were injected intravenously in CA and TP groups with 10 mg/kg, respectively. Cortex of 6 rats in each group was harvested at 12 hours and 72 hours after ROSC. Cortex of sham group was harvested at 72 hours after operation without VF induction. The expressions of phosphorylated JNK1/2 (p-JNK1/2), JNK1/2, caspase-3, Bax and Bcl-2 were measured by Western Blot. Cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL), and p-JNK/TUNEL double positive cells were detected by fluorescence double staining. RESULTS: Compared with sham group, the expressions of p-JNK, caspase-3 and Bax were increased, the expression of Bcl-2 was declined, and the apoptotic cells were significantly increased at 72 hours after ROSC in CA group. Compared with CA group, the phosphorylation of JNK was significantly declined at 12 hours and 72 hours after ROSC in TP group (the ratio of p-JNK1/2 and JNK1/2: 3.200±0.060 vs. 5.700±0.210, 1.400±0.060 vs. 5.400±0.090, both P < 0.05), the expressions of caspase-3 and Bax were decreased [caspase-3 (gray value): 42.00±5.23 vs. 54.00±7.84, 38.74±4.60 vs. 58.68±7.19; Bax (gray value): 38.04±6.21 vs. 68.76±6.08, 58.84±7.99 vs. 70.03±7.36, all P < 0.05], the expression of Bcl-2 was increased (gray value: 37.36±3.11 vs. 28.47±7.46, 48.78±6.55 vs. 29.54±3.13, both P < 0.05); the cell apoptosis rate was reduced at 72 hours [(31.14±4.51)% vs. (45.87±3.95)%, P < 0.01], and p-JNK/TUNEL double positive cells/TUNEL cells ratio was significantly decreased (10.00±0.85 vs. 52.70±3.05, P < 0.01). CONCLUSIONS: The inhibition of neuron apoptosis caused by TP after CPR in rats with CA is related to the inhibition of JNK1/2 phosphorylation.
