Objective To clarify the signaling mechanisms underlying angiotensin Ⅱ biphasic regulation of renal proximal Na+-HCO3- transport. Methods Different concentration Ang Ⅱ to the responses of Na+-HCO3- cotransporter (NBC) activity in isolated proximal tubules, with or without ATR, MAPK, cPLA2α, P450 blockade was compared in wild-type and Ang Ⅱ type 1a receptor (AT1aR)-deficient mice. The phospholipase of ERK was examined by Western blotting. AT1aR mRNA was examined by RT-PCR from kidney proximal tubules. Results (1)In isolated wild-type mouse, renal proximal tubules showed biphasic effects of Ang Ⅱ on NBC activity. Low concentration Ang Ⅱ (10-10 mol/L) increased NBC activity, but high concentration Ang Ⅱ (10-6 mol/L) decreased NBC activity. Olmcsartan (AT1 antagonist) blocked both stimnlatory and inhibitory effects of Ang Ⅱ on NBC activity, but PD98059 (mitogen-activated protein kinase inhibitor) blocked only the stimulatory effect of low concentration Ang Ⅱ ( 10-10 mol/L). (2)In AT1aR-deficient mice, only the stimulatory effect by high concentration of Ang Ⅱ (10-6 mol/L) was observed, which was blocked by olmesartan and PD98059. (3)In wild-type mice, pharmacological blockade of cPLA2 or P450 converted the inhibition effect by high concentration Ang Ⅱ (10-6 mol/L) to the stimulation, which was blocked by olmesanan and PD98059. These results indicated that the extracellular sigual-regulated kinase (ERK) activation via AT1 mediated only the stimulatory effect of Ang Ⅱ, while the cPLA2α/P450 activation via AT1 mediated the inhibitory effect of Ang Ⅱ independently of ERK. The analysis of ERK phosphorylation by Ang Ⅱ also supported a view that the cPLA2α/P450 pathway worked to suppress the ERK activation. Conclusions Ang Ⅱ activates ERK and cPLA2α with different concentration dependency via AT1. The balance between ERK and cPLA2α activities determines the final responses to Ang Ⅱ in intact proximal tubules.

Objective To investigate the clinical characteristic of vernier acuity in age-related macular degeneration (AMD) patients. Methods The vernier acuity test soft wear system was developed to detect the 23 cases (39 eyes) of AMD patients. Tweenty-one eyes were atrophic type and 17 eyes were exudative type. Two fixed targets and a movable target are shown on the computer screen. The examinee was asked to adjust the position of the central target and the relationship between it and align them by using a track ball. The computer automatically recorded the deviations of distances between the movable target and the specific one, and then computed and analysed the results of average threshold and variance. Results Both the atrophic and exudative AMD had higher vernier acuity threshold and its variance than normal subjects, and the differences were significant (P

Ebola virus (EBOV) causes hemorrhagic fever, resulting in mortality rates as high as 90% among infected humans and non-human primates (NHPs). The 2014 Ebola epidemic in West Africa is the severest in history, leading to WHO taking all control measures to stop any possibility of cross-border outbreaks. Because no licensed vaccines or effective therapeutics against EBOV are available, the current outbreak management has been limited to palliative care and barrier methods to prevent transmission. Several promising experimental EBOV vaccines have demonstrated protection in NHPs against lethal EBOV challenge, and some progresses have been made through clinical trials of EBOV vaccine candidates. It is believed there will be some licensed vaccine available in the near future to control EBOV outbreaks. In this review we provide some insights for further development of EBOV vaccines.
Animals ; Ebola Vaccines ; Ebolavirus ; Hemorrhagic Fever, Ebola ; prevention & control ; Humans

In medicine, it is the physician's obligation to promote and protect the patient's interest. In obstetrics, the ethical principles of beneficence and autonomy provide the fundamental framework which guides the management of all pregnant patients. As there is the need for consideration of the fetus, autonomy can become a complex issue giving rise to what is sometimes called "maternal-fetal conflict." In this paper, we aim to discuss some scenarios we encounter in our day-to-day obstetric practice such as pre-eclampsia, fetal growth restriction and labour induction when the best interests of the mother and fetus may be conflicted. We hope to illustrate that logical consideration for maternal and fetal best interests is only possible when there is adequate knowledge to support clinical practice. Certainly, with the rapid availability of newer knowledge and technology, it is the duty of the physician to be educated continuously so as to protect the patient from harm.
Beneficence ; Clinical Competence ; Conflict (Psychology) ; Ethics, Medical ; Female ; Fetal Growth Retardation ; Fetus ; Health Knowledge, Attitudes, Practice ; Humans ; Maternal Welfare ; Maternal-Fetal Relations ; Obstetrics ; ethics ; methods ; Patient Care ; ethics ; Patient Rights ; Personal Autonomy ; Physician-Patient Relations ; ethics ; Pregnancy ; Pregnancy Complications ; Prenatal Diagnosis

Salt reduction is one of the effective strategy for chronic non-communicable disease control and prevention recommended by World Health Organization. Research evidences on salt reduction emerge recently and some issues remain controversial. With the aim of providing reference for the future salt reduction action, this article reviewed the current evidence and strategies on the source of salt intake, the relationship between salt and health, the cost-effectiveness of salt reduction, as well as the targets and strategies of salt reduction. It also elaborated the main controversial issues in salt reduction, including salt reduction in population, evaluation method of salt intake, substitute salt, iodine intake, and the effectiveness of salt reduction strategy. The international and internal salt reduction activities were introduced as well.

Cytotoxic T cells (CTLs) play a key role in the control of Hepatitis B virus (HBV) infection and viral clearance. However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia. As HBV core protein (HBc) is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool covering HBc to screen and identify specific CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141-149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti-HBV activity were further determined in HBV and HLA-A2 transgenic mice. Finally, we show that mutations in HBc141-149 epitope are associated with viral parameters and disease progression in HBV infected patients. Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.
Adult ; Amino Acid Sequence ; Animals ; Binding Sites ; Epitopes ; chemistry ; immunology ; metabolism ; Female ; Genotype ; HEK293 Cells ; HLA-A2 Antigen ; metabolism ; Hepatitis B Core Antigens ; chemistry ; immunology ; metabolism ; Hepatitis B virus ; genetics ; metabolism ; Humans ; Hydrogen Bonding ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Middle Aged ; Molecular Dynamics Simulation ; Mutation ; Protein Binding ; Protein Structure, Tertiary ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism

Animals ; China ; Humans ; Immunophenotyping ; Influenza A Virus, H7N9 Subtype ; classification ; genetics ; immunology ; Influenza A virus ; classification ; genetics ; immunology ; Phylogeny

OBJECTIVETo investigate the effect of dietary saturated fat (SFA) from animal sources on the urine excretion 11-dehydro thromboxane B2 (TXB2) and 6-keto prostaglandin F 1alpha (PGF 1alpha) in 27 healthy free-living male subjects aged 30 to 55 years.

METHODSIt was a randomized crossover design. Each volunteer was randomly assigned to one of the two diets (high fat and low fat) for a period of 4 weeks, after which each subject resumed his usual diet for 2 weeks as a 'wash-out period', before being assigned to the other diet for an additional 4 weeks.

RESULTSSerum proportion of 20:4n-6 was 5% lower in the high fat (6.2% of total fatty acid) than in the low fat diet (6.5% of total fatty acid), which was associated with a significantly decreased ratio of the urinary excretion 11-dehydro TXB2 to 6-keto PGF 1alpha (P < 0.05). However, there was no significant fall in the absolute urinary excretion of 11-dehydro TXB2.

CONCLUSIONSDiet rich in SFA from animal sources may influence TXA2 formation via effect on tissue proportion of 20:4n-6.

6-Ketoprostaglandin F1 alpha ; urine ; Adult ; Arteriosclerosis ; physiopathology ; Cross-Over Studies ; Dietary Fats ; pharmacology ; Fatty Acids ; metabolism ; Humans ; Male ; Middle Aged ; Thrombosis ; physiopathology ; Thromboxane B2 ; analogs & derivatives ; urine

LZ-8 protein, isolated from a well known Chinese traditional medicinal fungus Ganoderma lucidum, is the first member of fungal immunomodulatory protein, members of which have been isolated from a variety of medicinal and edible mushrooms in the last two decades. The protein plays a multifunctional and important role in modulating immune system. In this report, in order to get LZ-8 protein crystals, the LZ-8 gene was expressed and purified by affinity chromatography, gel filtration chromatography and anion exchange chromatography subsequently. The protein was then crystallized using the hanging-drop vapour-diffusion method. The LZ-8 crystals were obtained and the phase information was calculated by X-ray diffraction. The resolution of LZ-8 crystals is 3.2A. This study will provide an insight into the structure of fungal immunomodulatory proteins.
Animals ; Crystallography ; Fungal Proteins ; biosynthesis ; genetics ; immunology ; Ganoderma ; genetics ; metabolism ; Genetic Vectors ; genetics ; Immunologic Factors ; biosynthesis ; genetics ; Mice ; Recombinant Proteins ; biosynthesis ; genetics ; immunology

INTRODUCTIONFetal imaging has improved with the development of faster magnetic resonance imaging (MRI) sequences, obviating the requirement for sedation. It is useful in characterising abnormality of the central nervous system in fetuses with abnormal or equivocal antenatal ultrasound findings. We reviewed all cases of fetal brain and spine MRI performed in our institution.

MATERIALS AND METHODSAll cases of fetal central nervous system MRI imaging from May 2006 to December 2008 were retrospectively reviewed, including fetal MRI, postnatal MRI and autopsy findings.

RESULTSThirty-one fetuses were imaged with MRI for evaluation of the central nervous system of which 3 were specifically for spinal evaluation. On fetal MRI, there were 11 normal fetuses (2 with minor ventricular asymmetry), 4 fetuses with minor ventriculomegaly and 16 fetuses with significant abnormalities. Twenty-three fetuses were delivered and 8 were terminated. Fifteen of 23 babies underwent postnatal imaging, 21 had clinical follow-up and 2 were lost to clinical follow-up. Of the 11 fetuses reported as normal on fetal MRI, 3 had additional postnatal findings. A fetus with a megacisterna magna on fetal MRI was diagnosed with a posterior fossa arachnoid cyst on postnatal MRI. One, who had fetal MRI to assess suspected absent inferior cerebellar vermis, had intracranial calcifications from rubella infection. One was diagnosed with cerebro-occular-facio-skeletal (COFS) syndrome postnatally, 1 was lost to follow-up and the rest were discharged well. Seven out of 16 fetuses with significantly abnormal fetal MRI findings had confirmation of the findings on postnatal imaging. Postnatal MRI detected 2 cases of polymicrogyria which were not seen on fetal MRI. Autopsy was available in 1 abortus confirming intrauterine diagnosis of Dandy Walker malformation. A myelomeningocele was clinically obvious in 1 abortus.

CONCLUSIONFetal MRI is a good method of assessing brain and spine abnormalities in utero. However, disorders of neuronal migration remain a challenging diagnostic problem in fetal imaging.

Central Nervous System ; abnormalities ; Fetus ; Humans ; Infant, Newborn ; Magnetic Resonance Imaging ; Malformations of Cortical Development ; diagnosis ; epidemiology ; physiopathology ; Medical Audit ; Retrospective Studies ; Singapore ; epidemiology