The variation of cancellous bones at lumbar vertebra,femoral neck,mandibular angle and rib in ovariectomized sheep

This study aimed to compare the variation of cancellous bones at four skeletal sites: lumbar vertebra, femoral neck, mandibular angle and rib in ovariectomized sheep. Sixteen adult sheep were randomly divided into two groups: eight sheep were ovariectomized served as experimental group; the other eight untreated sheep were served as control group. Bone mineral density was assessed by dual-energy X-ray absorptiometry on lumbar vertebrae at baseline and twelve months after ovariectomy. After 12 months, lumbar vertebrae L3 and L4, femoral necks, mandibular angles and the fourth ribs were harvested for micro-CT scanning, histological analysis and biomechanical test. The results showed that bone mineral density of lumbar vertebra decreased significantly in twelfth month (p < 0.05). The results of micro-CT showed that the bone volume/total volume decreased by 45.6%, 36.1% 21.3% and 18.7% in lumbar vertebrae, femoral necks, mandibular angles and ribs in experimental group (p < 0.05) respectively. The trabecular number showed the same downtrend (p < 0.05). Histological analysis showed trabecular area/tissue area decreased by 32.1%, 23.2% and 20.7% in lumbar vertebrae, femoral necks and mandibular angles respectively (p < 0.05), but no significant difference in ribs. Specimens elastic modulus from lumbar vertebra, femoral neck and mandibular angle were 952 ± 76 MPa (628 ± 70 MPa), 961 ± 173 MPa (610 ± 72 MPa) and 595 ± 60 MPa (444 ± 31 MPa) in control group (experimental group) respectively. These datum indicated that the sensibility of cancellous bones to oestrogen deficiency in ovariectomized sheep was site-specific on a pattern as follows: lumbar vertebra, femoral neck, mandibular angle and rib.     

Synthesis and biological effects of 2''-fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil.

2'-Fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil (FEAU) was synthesized, and its biological activities were compared with those of 2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU). Earlier studies indicated that both compounds showed potent anti-herpes simplex virus activity, with a 50% effective dose (ED50) of less than 0.25 microM. In the present study the cell growth inhibitory activity of FEAU (ED50, 200 to 2,060 microM) was found to be about 100-fold less than that of FMAU. With an ED50 ranging from 630 to 3,700 microM, FEAU only weakly inhibited thymidine incorporation into DNA, as compared with FMAU with an ED50 of 9 to 28 microM. Following exposure to [2-14C]FEAU (100 microM), 0.48 pmol/10(6) cells per h was incorporated into the DNA of herpes simplex virus type 1-infected Vero cells, whereas no detectable incorporation was found in uninfected Vero cells or L1210 cells. The Ki of FEAU for thymidine kinase purified from human leukemic cells was greater than 150 microM. For herpes simplex virus type 1- and 2-encoded thymidine kinases, the Kis were 0.6 and 0.74 microM, respectively. Both FEAU and FMAU were relatively nontoxic for mice, with a 50% lethal dose of greater than 800 mg/kg per day (four intraperitoneal doses). However, the lethal dose of FEAU for dogs was 100 mg/kg per day (10 intravenous doses), a dose which is 40- to 80-fold greater than the toxic dose of FMAU. These results suggest that FEAU is a worthy candidate for further development as an antiherpetic agent.     

A pilot study of functional magnetic resonance imaging of the brain during manual and electroacupuncture stimulation of acupuncture point (LI-4 Hegu) in normal subjects reveals differential brain activation between methods

OBJECTIVES: To characterize the brain activation patterns evoked by manual and electroacupuncture on normal human subjects. DESIGN: We used functional magnetic resonance imaging (fMRI) to investigate the brain regions involved in electroacupuncture and manual acupuncture needle stimulation. A block design was adopted for the study. Each functional run consists of 5 minutes, starting with 1-minute baseline and two 1-minute stimulation, the interval between the two stimuli was 1 minute. Four functional runs were performed on each subject, two runs for electroacupuncture and two runs for manual acupuncture. The order of the two modalities was randomized among subjects. During the experiment, acupuncture needle manipulation was performed at Large Intestine 4 (LI4, Hegu) on the left hand. For each subject, before scanning started, the needle was inserted perpendicular to the skin surface to a depth of approximately 1.0 cm. Electroacupuncture stimulation was delivered using a continuous rectangular wave form (pulse width 30 ms) at a frequency of 3 Hz. For manual acupuncture, the needle was rotated manually clockwise and counterclockwise at a rate of about 180 times per minute (3 Hz). SUBJECTS: Eleven right-handed, normal, healthy volunteer adults, 6 male and 5 female, ages 21-64 participated in the experiment. RESULTS: Results showed that electroacupuncture mainly produced fMRI signal increases in precentral gyrus, postcentral gyrus/inferior parietal lobule, and putamen/insula; in contrast, manual needle manipulation produced prominent decreases of fMRI signals in posterior cingulate, superior temporal gyrus, putamen/insula. CONCLUSION: These results indicate that different brain networks are involved during manual and electroacupuncture stimulation. It suggests that different brain mechanisms may be recruited during manual and electroacupuncture.     

Experimental autoimmune thyroiditis. In vitro cytotoxic effects of T lymphocytes on thyroid monolayers

Effector mechanisms in experimental autoimmune thyroiditis (EAT) were studied in vitro by establishing a cytotoxicity system with thyroid target cells. Lymph node cells (LNC) from popliteal and inguinal lymph nodes were obtained from CBA/J mice (8-10 wk old) 12-18 d after immunization with 120 micrograms mouse thyroglobulin (MTg) in complete Freund's adjuvant (0.2 ml to both hind footpads and thighs) and were cultured with MTg (10-50 micrograms/ml). On day 5 of culture, viable LNC were added to labeled thyroid monolayers and their cytoxicity was assayed after 16 h. Functional thyroid target cells, as reflected by MTg production for up to 9 d, were prepared by adding 1 mM dibutyryl adenosine 3',5'-cyclic monophosphate and 60 microU thyroid-stimulating hormone/ml to the culture medium. On days 5-7, confluent monolayers were labeled with 111In and used as targets. Specific 111In-release ranged from 56 to 85%. The cytotoxic response is MTg specific and H-2 restricted. Pretreatment of thyroid target cells with rabbit antiserum to MTg completely inhibited cytotoxicity. Pretreatment with mouse antiserum to either Kk or Dk products resulted in approximately 50% inhibition, whereas the combined use of both antisera led to total inhibition. No cytotoxicity was observed when control BALB/c thyroid cultures were the target cells. The kinetics of the expansion of Thy-1+ cytotoxic cells by in vitro exposure to MTg were then studied. The cytotoxic response required 5 d to develop and was abolished by treating LNC on day 4 with monoclonal antibody to Lyt-1.1, but not to Lyt-2.1, plus complement. In contrast, by day 5, cytotoxicity was abrogated by similar treatment with antiserum to Lyt-2.1, but not to Lyt-1.1. We conclude that cytotoxic cells derived from MTg-immunized mice are Lyt-2-bearing cells but require the presence of Lyt-1-bearing cells for their generation and/or differentiation.     

Influences of different vasopressors on stroke volume variation and pulse pressure variation

Pulse pressure variation (PPV) and stroke volume variation (SVV) during mechanical ventilation have been shown to be effective parameters to predict preload responsiveness. Although induced hypertension decreases PPV and SVV, the influences of different vasopressors on PPV and SVV are unknown. 94 patients undergoing elective otologic surgery were randomly divided into three groups: Group P (patients were given phenylephrine), Group D (patients were given dopamine), Group E (patients were given ephedrine). When surgery was ongoing and the circulation state was stable, patients were given the vasopressor to increase the systolic arterial pressure (SAP) to the pre-calculated levels: low level, 10 % < ΔSAP ≤ 20 %; medium level, 20 % < ΔSAP ≤ 30 %; high level, 30 % < ΔSAP ≤ 40 %. When invasive arterial pressure reached the target value, PPV, SVV and other parameters were recorded. Dopamine decreased the PPV and SVV more significantly than ephedrine, but less significantly than phenylephrine. The influences of phenylephrine, dopamine and ephedrine on SVV and PPV are different due to their different pharmacological mechanisms.     

Risk factors for infection in Malaysian patients with systemic lupus erythematosus

To determine the incidence, types and risk factors for infection in systemic lupus erythematosus (SLE) patients in Kuala Lumpur, Malaysia, we retrospectively reviewed the medical records of 102 patients with definite SLE attending a specialist clinic. Details of major infections (pneumonia or severe infection requiring intravenous therapy) and minor infections, and their time of onset in relation to immunosuppressive therapy and disease flares were recorded. There were 77 major and 163 minor infections during 564 patient-years of follow-up. In the month following a course of pulse methylprednisolone, the incidence of major infection was 20 times higher and the incidence of minor infection was 10 times higher than at other periods (p&lt;0.0001). In the month after disease flare, the incidence of major infection was 10 times higher and the incidence of minor infection six times higher than at other times (p&lt;0.0001). After allowing for methylprednisolone therapy and disease flares, there was no increase in the rate of infections during treatment with azathioprine, oral or intravenous cyclophosphamide. There was no effect of renal involvement on infection rate.      

经后路全内镜技术治疗腰椎间盘突出症86例疗效观察

目的 探讨后路全内镜(Full Endoscopic,FE)技术取除突出髓核组织治疗腰椎间盘突出症的可行性及有效性.方法 2012年8月至2013年8月共收治经临床确诊为单节段腰椎间盘突出症患者86例,腰4/5节段35例、腰5骶1节段51例.采用后路全内镜技术取出突出髓核组织的治疗方法,根据术后腰痛及腿痛缓解情况、下床活动及住院时间评估恢复效果.手术前后采用VAS评分评价患者腰痛缓解情况,ODI评分评价患者腿痛及日常工作与生活情况.结果 84例患者顺利完成手术,术后下床时间8 ～ 12h,平均10 h;术后住院时间为2～4d,平均3d;术后2周恢复非体力劳动的工作.84例患者均无神经根、硬膜损伤及其它手术并发症发生,均获随访,随访时间6 ～12个月.与术前相比,术后VAS评分及ODI评分明显改善(P＜0.05).另2例患者改开放手术.结论 采取后路全内镜下技术取出突出髓核组织治疗腰椎间盘突出症具有创伤小、神经根减压充分、出血少,恢复快等优点,体现了外科微创手术有的放矢、立竿见影的确切效果.     

Role of transcriptional factor Nrf2 in the acute lung injury of mice

Objective: This study aimed to investigate the expression and role of Nrf2 in the acute lung injury (ALI) of mice. Methods: A total of 60 BABL/c mice were randomly divided into 2 groups: ALI group and control group. In ALI group, ALI was introduced by injection of LPS. Immunohistochemistry was performed to detect Nrf2 expression in the lung; Western blot assay was employed to detect the expression of Nrf2 in the lung homogenate; ELISA was conducted to detect the expression of Nrf2 in the lung homogenate and BALF. Results: As compared to control group, ALI mice had a high Nrf2 expression in the lung as shown in immunohistochemistry, and the Nrf2 expression in the lung homogenate and BALF also increased markedly (P<0.05). Conclusion: The Nrf2 expression increases in the lung and BALF of ALI mice, suggesting that Nrf2 is involved in the inflammation during ALI and may serve as a new target in the therapy of ALI.     

Susceptibilities of Genotype 1a, 1b,and 3 Hepatitis C Virus Variants to the NS5A Inhibitor Elbasvir

Elbasvir is an investigational NS5A inhibitor with in vitro activity against multiple HCV genotypes. Antiviral activity of elbasvir was measured in replicons derived from wild-type or resistant variants of genotypes 1a, 1b, and 3. The barrier to resistance was assessed by the number of resistant colonies selected by exposure to various elbasvir concentrations. In a phase 1b dose-escalating study, virologic responses were determined in 48 noncirrhotic adult men with chronic genotype 1 or 3 infections randomized to placebo or elbasvir from 5 to 50 mg (genotype 1) or 10 to 100 mg (genotype 3) once daily for 5 days. The NS5A gene was sequenced from plasma specimens obtained before, during, and after treatment. Elbasvir suppressed the emergence of resistance-associated variants (RAVs) in vitro in a dose-dependent manner. Variants selected by exposure to high elbasvir concentrations typically encoded multiple amino acid substitutions (most commonly involving loci 30, 31, and 93), conferring high-level elbasvir resistance. In the monotherapy study, patients with genotype 1b had greater reductions in HCV RNA levels than patients with genotype 1a at all elbasvir doses; responses in patients with genotype 3 were generally less pronounced than for genotype 1, particularly at lower elbasvir doses. M28T, Q30R, L31V, and Y93H in genotype 1a, L31V and Y93H in genotype 1b, and A30K, L31F, and Y93H in genotype 3 were the predominant RAVs selected by elbasvir monotherapy. Virologic findings in patients were consistent with the preclinical observations. NS5A-RAVs emerged most often at amino acid positions 28, 30, 31, and 93 in both the laboratory and clinical trial. (The MK-8742 P002 trial has been registered at ClinicalTrials.gov under identifier {"type":"clinical-trial","attrs":{"text":"NCT01532973","term_id":"NCT01532973"}}NCT01532973.)