Pressure-sensitive multivesicular liposomes as a smart drug-delivery system for high-altitude pulmonary edema.

Changes in bodily fluid pressures, such as pulmonary artery pressure, play key roles in high-altitude pulmonary edema (HAPE) and other disorders. Smart delivery systems releasing a drug in response to these pressures might facilitate early medical interventions. However, pressure-responsive delivery systems are unavailable. We here constructed hydrostatic pressure-sensitive multivesicular liposomes (PSMVLs) based on the incomplete filling of the internal vesicle space with neutral lipids. These liposomes were loaded with amlodipine besylate (AB), a next-generation calcium channel inhibitor, to treat HAPE on time. AB-loaded PSMVLs (AB-PSMVLs) were destroyed, and AB was released through treatment under hydrostatic pressure of at least 25 mmHg. At 25 mmHg, which is the minimum pulmonary artery pressure value in HAPE, 38.8% of AB was released within 1 h. In a mouse HAPE model, AB-PSMVLs concentrated in the lung and released AB to diffuse into the vascular wall. Intravenously injected AB-PSMVLs before HAPE modeling resulted in a stronger protection of lung tissues and respiratory function and lower occurrence of pulmonary edema than treatment with free drug or non-pressure-sensitive AB-loaded liposomes. This study offers a new strategy for developing smart drug delivery systems that respond to changes in bodily fluid pressures.

Acute ischemic stroke due to unruptured small aneurysm of internal carotid artery: A case report.

RATIONALE: Intracranial small aneurysm is a rare cause of ischemic stroke, and been described only in sparse case reports. The exact pathophysiology, treatment strategies, and prognosis remain incompletely understood. PATIENT CONCERNS: A 42-year-old man presented with an acute onset weakness of the right limbs. DIAGNOSES: Neuroimaging evaluation confirmed a diagnosis of acute ischemic stroke and left internal carotid artery (ICA) small aneurysm. INTERVENTIONS: The patient underwent oral anti-platelet therapy (100 mg aspirin daily). OUTCOMES: The patient recovered to normal status within 4 weeks following antiplatelet treatment. During a follow-up period of 1 year, he remained neurologically asymptomatic and led a virtually normal life. LESSONS: It is crucial for clinicians to be aware of this entity, as cerebral infarction caused by small cerebral aneurysm is extremely rare.

Resveratrol ameliorates brain injury via the TGF-ß-mediated ERK signaling pathway in a rat model of cerebral hemorrhage.

Brain injury is the most common intracranial injury in human cerebrovascular disease, which may lead to ischemic stroke. Resveratrol induces ameliorative effects in the treatment of certain human diseases by regulating different signaling pathways. The present study assessed the therapeutic effects of resveratrol and its potential mechanism of action in the neurons from rats with ischemia/reperfusion-induced cerebral hemorrhage. The rat model of cerebral hemorrhage was established and reverse transcription-quantitative polymerase chain reaction, western blotting, immunohistochemistry and terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling assays were subsequently performed to assess the therapeutic effects of resveratrol. The results demonstrated that treatment with resveratrol (10 mg/kg/day) decreased cerebral water content, hippocampal cell apoptosis and cerebral infarct volume compared with the PBS-treated group. Resveratrol treatment also increased neuronal cell viability, improved neurological function and blood brain barrier disruption compared with the PBS group following 21 days of treatment. The administration of resveratrol was demonstrated to decrease the levels of certain inflammatory factors, including ionized calcium binding adaptor molecule 1 and myeloperoxidase, in rats with cerebral hemorrhage. The results revealed that treatment with resveratrol regulated neuronal apoptosis by downregulating the transforming growth factor-ß (TGF-ß)-mediated extracellular signal-regulated kinase (ERK) signaling pathway. In conclusion, these results indicate that resveratrol decreases ischemia/reperfusion-induced neuronal apoptosis by downregulating the TGF-ß-mediated ERK pathway in a rat model of cerebral hemorrhage and may serve as a potential agent for the treatment of cerebral hemorrhage.

Baicalein inhibits interleukin-1ß-induced proliferation of human rheumatoid arthritis fibroblast-like synoviocytes.

Baicalein shows anti-inflammatory effects in human rheumatoid arthritis fibroblast-like synoviocytes (RAFLS). Considering its anti-proliferatory effects on various cancer cells, we investigated the effects of baicalein on interleukin-1 beta (IL-1ß)-induced proliferation of human RAFLS. Cell proliferation was examined by (3)H-thymidine incorporation assay. Western blot analysis was performed to assess the phosphorylation of extracellular regulating kinase (ERK), p38, and c-Jun N-terminal kinase, and nuclear translocation of nuclear factor kappa B (NF-κB) subunit p65. Notably, baicalein significantly suppressed IL-1ß-mediated RAFLS proliferation (P < 0.05), along with reduced ERK1/2 and p38 phosphorylation. The IL-1ß-induced p65 nuclear translocation and NF-κB DNA binding activity was significantly decreased by baicalein. Additionally, the inhibitory effects of baicalein on IL-1ß-induced proliferation of RAFLS were dose-dependently reversed by the addition of recombinant macrophage migration inhibitory factory (MIF). Our results indicate that baicalein inhibits IL-1ß-induced RAFLS proliferation, which involves suppression of NF-κB transcriptional activity and MIF-mediated signaling.

[Fluvastatin's effect on atherogenesis in apolipoprotein-E knockout mice infected by cytomegalovirus].

OBJECTIVE: The goal of this study was to investigate whether murine cytomegalovirus (MCMV) is able to exacerbate the atherosclerotic process in apolipoprotein E knockout (apoE -/-) mice, and the effect of fluvastatin on the atherogenesis. METHODS: The apoE-/- mice kept on a west diet were given low dosage of MCMV. At 14,18 and 24 weeks post infection, AS lesion were measured on aorta. The fluvastatin was administered, and AS lesion were measured accordingly above. RESULTS: We observed that in the chronic phase of the infection, AS lesion area was significantly increased. MCMV gB mRNA was not amplified by real-time PCR from the arterial wall. The IgG antibody level of MCMV in blood plasma and the content of virus DNA in salivary gland were not correlated with AS lesions. After the administration of fluvastatin, there was no significant difference of AS lesions between MCMV infected group and mock-infected group. CONCLUSION: MCMV may aggravate the AS lesion in apoE -/- mice in the chronic phase of infection, and promote more severe type of AS lesions. But it might not be the direct effects of mechanism of MCMV on the local lesion of AS. Fluvastatin could meliorate the progression of AS after MCMV infection, but this was not accomplished by decreasing MCMV duplication.

[Relationship between EB virus, Cytomegalo virus, herpes simplex virus and coxsackievirus infection and relapse of multiple sclerosis].

OBJECTIVE: To study the relation between the recent active infection with Epstein-Barr virus, cytomegalovirus,herpes simplex virus-1, coxsackievirus B I-IV and the relapse of relapsing-remitting multiple sclerosis (RR MS). METHODS: Using ELISA method, IgM antibodies to Epstein-Barr virus, cytomegalovirus, herpes simplex virus-1, coxsackievirus BI-IV in the plasma from 34 RR MS patients and 200 normal controls were detected. The rates of recent active infection with the above mentioned viruses of the patients and controls were compared.For patients group,comparison was also made between the clinical data of recent active infected patients and patients without recent active infection. RESULTS: There was no statistically significant difference in positive rates of positive rates of IgM antibodies against Epstein-Barr virus, cytomegalovirus, herpes simplex virus-1 and coxsackievirus BI, II, III or VI between the two groups. While there was statistically significant difference in positive rates of IgM antibodies to coxsackievirus B VI and V in the RR MS patients and those in the controls (being 3/34 and 0/200 P < 0.05; 2/34 and 0/200 P < 0.05, respectively). In the patient group, when patients who had active infection with any of the viruses were compared with those who had no active infection, no significant difference between them was found in terms of age, course, frequency, body temperature on admission, differential leukocyte count (neutrophilic granulocyte, lymphocyte and monocytes), use of glucocorticoids, and EDSS point value. CONCLUSIONS: There is a high rate of recent active infection with coxsackievirus B VI and V in RR MS patients at relapsing stage. While the recent virus active infection is unrelated to the severity of the symptoms.