Effects of dl-3-n-butylphthalide on serum lipoprotein-associated phospholipase A2 and hypersensitive C-reactive protein levels in acute cerebral infarction.

OBJECTIVE: This study aims to explore the curative effect of dl-3-n-butylphthalide (NBP) on patients with acute cerebral infarction (ACI) and its effects on serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and hypersensitive C-reactive protein (hs-CRP) levels. METHODS: A total of 136 ACI patients treated in our hospital, who met the criteria, were selected and randomly divided into two groups: control group (n = 60, including 28 males and 32 females) and treatment group (n = 76, including 32 males and 44 females). Patients in the control group were treated with routine drug therapy, while patients in the treatment group were treated with NBP on this basis. A dose of 100 ml was administered by intravenous injection for 2 times/day, for 14 days. The curative effect was evaluated using the National Institute of Health Stroke Scale (NIHSS) and Barthel index (BI) self-care ability. The levels of the two factors in serum were measured using enzyme-linked immunosorbent assay, and the changes in levels of these two factors in serum at different time points before and after treatment were compared between the two groups. RESULTS: (a) Lp-PLA2 and hs-CRP levels in the treatment group after treatment were significantly lower than those before treatment and those in the control group after treatment (p < .05). (b) The NIHSS and BI scores in the treatment group were significantly lower after treatment than before treatment and those in the control group after treatment (p < .05). CONCLUSION: Dl-3-n-butylphthalide can improve the expression of Lp-PLA2 and hs-CRP in serum in ACI patients. Furthermore, NBP has significant efficacy in inhibiting inflammation and improving neurological symptoms.

Theoretical explanation for the pharmaceutical incompatibility through the cooperativity effect of the drug-drug intermolecular interactions in the phenobarbital∙∙∙paracetamol∙∙∙H2O complex.

In order to reveal the essence of the pharmaceutical incompatibility, the cooperativity effects of the drug-drug intermolecular π∙∙∙π and H∙∙∙O H-bonding interactions involving hydration were evaluated in the phenobarbital∙∙∙paracetamol∙∙∙H2O complex at the M06-2X/6-311++G** and MP2/6-311++G** levels. The thermodynamic cooperativity effects were also investigated by the statistical thermodynamic method. The results show that the π∙∙∙π stacking ternary complexes with the moderate anti-cooperativity effects are dominant in controling the aggregation process of phenobarbital, paracetamol, and H2O, as is confirmed by the atoms-in-molecules (AIM) and reduced density gradient (RDG) analyses. Therefore, it can be inferred that the anti-cooperativity effect plays an important role in forming the pharmaceutical incompatibility, and thus a deduction on the formation process of the pharmaceutical incompatibility between phenobarbital and paracetamol, with the hydration effect, is given. Several valuable models that relate the features of molecular surface electrostatic potentials or their statistical parameters, such as the surface areas, average values ([Formula: see text]), variances ([Formula: see text], [Formula: see text] and [Formula: see text]), and product of [Formula: see text] and electrostatic balance parameter (ν) ([Formula: see text]ν), to the values of the cooperativity effects were predicted. The formation of the pharmaceutical incompatibility is a thermodynamic cooperativity process driven by the enthalpy change. Graphical abstract Anti-cooperativity effect plays an important role in forming the pharmaceutical incompatibility.

Dantrolene enhances the protective effect of hypothermia on cerebral cortex neurons.

Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is neuroprotective in in vitro and in vivo ischemic injury models. In addition to its neuroprotective effect, dantrolene neutralizes the adverse reaction of hypothermia. Dantrolene may be an effective adjunctive therapy to enhance the neuroprotection of hypothermia in treating ischemic stroke. Cortical neurons isolated from rat fetuses were exposed to 90 minutes of oxygen-glucose deprivation followed by reoxygenation. Neurons were treated with 40 µM dantrolene, hypothermia (at 33°C), or the combination of both for 12 hours. Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis. Furthermore, improvements in cell morphology were observed. The combined treatment enhanced these responses compared with either treatment alone. These findings indicate that dantrolene may be used as an effective adjunctive therapy to enhance the neuroprotective effects of hypothermia in ischemic stroke.

AcMNPV-mediated expression of BmK IT promotes the apoptosis of Sf9 cells and replication of AcMNPV.

Chinese scorpion Buthus martensii Karsch (BmK) venom is a rich source of neurotoxins which bind to various ion channels with high affinity and specificity and thus widely used as compounds to modulate channel gating or channel currents. To promote the insecticidal effects of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), the gene encoding an excitatory insect toxin, BmK IT, was inserted into the genome of AcMNPV to construct a recombinant baculovirus, AcMNPV-BmK IT. Spodopter frugiperda 9 (Sf9) cells were infected with AcMNPV and AcMNPV-BmK IT respectively for 24 h. Results from the MTT assay, TUNEL assay, analysis of the expression level of apoptosis-related proteins (c-Myc, cleaved-Caspase3, Bcl-2 and Bax) of Sf9 cells, the transcription level of key genes (38K, C42, P78, F) of AcMNPV, and viral propagation assay demonstrated that AcMNPV-mediated expression of BmK IT promoted the apoptosis of Sf9 cells and replication of AcMNPV. The results laid a foundation for further structural and functional analysis of BmK IT.

Molecular mechanism of hepatocellular carcinoma-specific antitumor activity of the novel thienopyridine derivative TP58.

Despite progress made in the treatment of hepatocellular carcinoma (HCC), there is no curable treatment. Novel therapies are therefore needed. In our previous study on the design and synthesis of a small molecular inhibitor targeting Aurora kinase, we discovered a novel thienopyridine derivative compound (1g, TP58) which displayed the most potent and relatively specific inhibition of the proliferation of HepG2 human hepatoma cells in vitro. However, the molecular mechanism remains to be elucidated. Herein, in vitro and in vivo studies were conducted to further verify its antitumor activity against HCC. cDNA microarray and two-dimensional protein gel electrophoresis technology were utilized to elucidate the mechanism of HCC-specific inhibition of TP58. Flow cytometry analysis displayed that TP58 can significantly induce G0/G1 arrest in HepG2 cells. Sixteen genes involved in cell cycle regulation were found to be dysregulated following TP58 treatment using microarray technology. Nine proteins whose expression was altered (corresponding to 10 spots identified as differentially expressed) were identified by proteomic analysis. Further study showed that TP58 can modulate the expression of some liver-enriched transcription factors (LETFs) and liver-specific marker genes, such as hepatic nuclear factor (HNF-4) and α-fetoprotein (AFP). These findings may help explain the mechanism of HCC-specific antitumor activity of TP58 and provide some useful insight for anti-HCC drug design and future use of thienopyridine derivatives in HCC therapy.

[Prevalence of sleep disorders among 3173 elderly in Taiyuan city: a cross-sectional study].

OBJECTIVE: To investigate the prevalence rates of sleep disorders and the correlative in the elderly from Taiyuan city. METHODS: All of the 3173 elderly (aged 60 years to 100 years) in Taiyuan city were investigated at home through questionnaires, regarding their sleep condition. Subjects with sleep disorders were then screened through questionnaires and reexamined/diagnosed by special doctors. RESULTS: (1) Among the 3173 elderly, 2132 subjects complained of having sleep disorders. The total prevalence of sleep disorders was 67.2%. The prevalence rates of chronic insomnia, multi-dreams, habitual snoring and daytime drowsiness were 39.65%, 38.58%, 26.66% and 34.32% respectively. (2) In the male elderly, the prevalence rates of being awaken early, having more urination at night, daytime drowsiness, sleep-respiratory disturbance and indiscriminate sleep rhythm increased with age (P < 0.01). However, in the female elderly, the prevalence rates of being awaken early, having daytime drowsiness and indiscriminate sleep rhythm also had a tendency of increase (P < 0.01). (3) Living alone, emotional disorder, pain and nocturia (P < 0.01) were the risk factors of chronic insomnia in the male elderly while living alone, numbness/pruritus (P < 0.01), emotional disorder (P < 0.05), were the risk factors of chronic insomnia in the female elderly. CONCLUSION: The prevalence rates of some sleep disturbances in the elderly in Taiyuan city were generally correspondent with prevalence rates reported elsewhere that called for more attention be paid to the effect of mood disturbance and diseases related to sleep condition among the elderly.

[The clinical research of restless leg syndrome and Parkinson's disease].

OBJECTIVES: To investigate the clinical feature of Parkinson's disease (PD) with restless leg syndrome (RLS) and the pathogenesis of RLS. METHODS: We conducted a cross-sectional and control study. The case group concluded 31 PD with RLS patients, meanwhile 39 PD patients were selected as the control group. Clinical history, clinical manifestations, complications and laboratory examinations were compared respectively between the two groups. RESULTS: All the RLS symptoms did not appear in RLS patients until the PD symptoms came out. Significant differences were found in complications such as swallow disturbance, constipation and illusion, when we compared the two PD groups (P < 0.05). Compared with the PD or healthy group, the level of serum ferritin and the H-reflex latency of tibial nerve were significantly decreased in PD with RLS group (P < 0.05). CONCLUSIONS: Secondary RLS is a complication of PD. Deficiency of iron and decreased inhibition function of spinal cord may lead to the occurrence of RLS in PD patients. When their motor symptoms are serious and complications are more common, PD patients are more possible to have RLS symptoms.