Lymphocyte Index of Peripheral Blood in Rats at Different Stages of the Post-Stress Period under Conditions of Antigenic Exposure and Injection of Lipopolysaccharide

Bulletin of Experimental Biology and Medicine - Changes in the Shaganin lymphocyte index (ratio of the number of lymphocytes to segmented neutrophils) in the peripheral blood of rats after...     

LC-MS/MS测定人血浆中对乙酰氨基酚及其人体药动学和生物等效性研究

目的 建立一种快速、灵敏的高效液相色谱-串联质谱（HPLC-MS/MS）方法以测定人血浆中对乙酰氨基酚浓度,并应用于两种对乙酰氨基酚制剂的人体药代动力学和生物等效性研究。方法 以替硝唑为内标,200μL血浆样品经5倍于其体积的乙酸乙酯液液萃取,再经Waters XBridge? C18柱等度洗脱分离后导入串联质谱,以正离子多反应监测模式进行定量分析,对乙酰氨基酚和内标的选择性反应离子对分别是m/z 152→110和248→121。方法经验证后应用于19名健康受试者单剂量空腹口服两种对乙酰氨基酚制剂500mg后药代动力学和生物等效性的研究。结果 血浆中对乙酰氨基酚在0.1～8.0 μg·mL-1范围内线性良好（r2 > 0.99）,最低检测限为 0.1 μg·mL-1,提取回收率为91.0%～98.7%,日内和日间准确度分别为98.8%～111.3% （精密度：CV ? 9.03%）和94.9%～102.6% （精密度：CV ? 10.68%）。生物等效性试验中,受试制剂与参比制剂的主要药代动力学参数Cmax、AUC0-t和AUC0-∞ 几何均值比的90%置信区间分别为83.50%～105.79%,94.25%～101.54%和93.24%～101.02%,均落在生物等效可接受标准80.00%～125.00%范围内。结论 所建立测定人血浆中对乙酰氨基酚浓度的HPLC-MS/MS法具有快速灵敏、回收率高、选择性好的特点,适用于对乙酰氨基酚片人体药代动力学和生物等效性研究。受试制剂与参比制剂在人体内吸收速度和程度相似,两种制剂生物等效。     

What are Journals for?

‘The secret is comprised in three words – work, finish, publish.’Michael FaradayThere are many reasons doctors want to publish their work. For most at an early stage in their career, this may be to add a line to their curriculum vitae and advance their careers but for academics, publishing is an expectation. Many will believe they have something important to say, and wish to provoke debate and discussion; others wish to share knowledge and experiences, which in medicine can lead to a satisfying change in clinical practice. All serve to register one’s idea and educate others. However, for some, the reason is as basic as money. As we celebrate the 350th anniversary of the first academic publication, perhaps we have come full circle when it comes to why people publish?Publishing is a flourishing business. There were approximately 28,100 active scholarly peer-reviewed journals in mid-2012, collectively publishing about 1.8–1.9 million articles per year. The number of articles published each year and the number of journals have both grown steadily for more than two centuries, by about 3% and 3.5% per year respectively.¹ Journals have a responsibility to refine and define information and act as a scientific filter. Many of us will receive daily invitations in our email inbox from eclectic and new journals that are likely to take anything – is the filter now too porous? But this industry is like any other commercial activity and the supply still far outstrips the demand. Perhaps the internet revolution has merely fuelled our hunger to publish more?The launch of this exciting and innovative series about publishing coincides with the 350th celebration of the publication of the first academic journal. In the age of social media, the first question is ‘What are journals for?’, which Simon Rallison sets out to answer. Simon is Director of Publications at the Physiological Society, and was previously a journal publisher with Earthscan, Springer and Blackwell.Writing is hard work and, through this series, I hope the reader will get some useful insight into this service industry for academia.Jyoti ShahCommissioning EditorIn an age of the internet and social media, why are we still using (admittedly with refinements and improvements) a form of publication dating from 1665? What exactly is a journal in the 21st century and what role does it have to perform? Surprisingly, the academic journal has not evolved since it was invented 350 years ago.¹ The first issue of the Philosophical Transactions of the Royal Society was published in 1665, the brainchild of Henry Oldenburg and Robert Hooke. Since then, journals have digitised and now offer greater opportunity for research communication – but are authors taking advantage of what journals can offer? The academic and research community is generally very conservative about what it reads and how it views journals. There are, however, also frequent misunderstandings about the operation of journals.     

Antiidiotypic IgG crossreactive with Rh alloantibodies in red cell autoimmunity

IgG autoantibodies eluted from RBCs of antiglobulin positive normal blood donors contained at least two antibody populations, an IgG autoantibody (Ab 1), and an IgG population (Ab 2) that agglutinated RBCs coated with some Rh(D) alloantibodies. Eight of 24 autoantibody eluates tested agglutinated 3 of 10 anti-Rh(D) sensitized RBCs. The agglutinating activity was inhibited specifically by preincubation of the autoantibody eluate with the reactive anti-D. The reaction did not require the Fc domain of the anti-Rh(D), since autoantibody eluates agglutinated RBCs coated with F(ab')2 prepared from the reactive anti-D sera. These findings indicate that the RBCs of some antiglobulin- positive blood donors contain an immunoglobulin auto-antiidiotype (Ab 2) against the RBC autoantibody (Ab 1) which is demonstrable through its cross-reactivity with selected Rh(D) alloantibodies. Identification of auto-antiidiotypes in RBC autoimmunity lends support to the idiotype- antiidiotype network hypothesis of immune regulation and is consistent with the bizarre and complex serology of autoimmune hemolytic anemia. The absence of clinical hemolysis in antiglobulin-positive normal blood donors suggests that immunoglobulin idiotype-antiidiotype interactions may play a role in modulating the effects of RBC autoimmunity.     

Persistent reversed end diastolic flow in the fetal middle cerebral artery: an ominous finding

Fetal persistent middle cerebral artery reversed end diastolic flow is a rare and ominous finding. Previous cases have been associated with intracranial hemorrhage, growth restriction, anaemia, and hepatic anomaly. Intrauterine demise or early neonatal death is a common outcome. We report the case of persistent middle cerebral artery reversed end diastolic flow in a well-grown fetus at 32 weeks’ gestation resulting from acute, severe anaemia due to a large feto-maternal hemorrhage. An emergency cesarean section was performed and the neonate required advanced resuscitation and immediate blood transfusion. Postnatal magnetic resonance imaging confirmed a hemorrhagic parietal infarct and bilateral ischaemic changes in the basal ganglia. This provides further evidence that persistent middle cerebral artery reversed end diastolic flow in any fetus is an ominous finding warranting urgent diagnostic evaluation and/or delivery.     

A New Insight into the Mechanism of 1,3‐Dienes Cationic Polymerization III: Polymerization of 1,3‐Pentadiene with CF3COOD/TiCl4 Initiating System: Chain‐Ends Structure and Kinetics

A novel method for the investigation of the chain‐end structure of poly(1,3‐pentadiene)s synthesized using the CF₃COOD/TiCl₄ initiating system is developed. It is shown for the first time that the content of trans‐1,2‐structures in the first monomer unit is considerably higher than the content of trans‐1,4‐structures, whereas the content of trans‐1,4‐units is substantially higher than trans‐1,2‐units for the polymer chain as a whole. Another important observation is that chain transfer to monomer is significant even at the earlier stages of the 1,3‐pentadiene polymerization (after 1 s of reaction). The very low functionality at the ω‐end (F_n (Cl) < 0.15) confirms the intensive chain transfer to monomer. This method is also applied for the estimation of the concentration of active species and the rate constant for propagation (k _p) for the cationic polymerization of 1,3‐pentadiene using the CF₃COOD/TiCl₄ initiating system: rate constants for propagation, k _p, of 1.5 × 10³ and 3.3 × 10³ L mol^?1 min^?1 are determined for 1,3‐pentadiene polymerization at 20 and –78 °C, respectively.

     

Prognostic value of paroxysmal nocturnal haemoglobinuria clone presence in aplastic anaemia patients treated with combined immunosuppression: results of two‐centre prospective study

Paroxysmal nocturnal haemoglobinuria (PNH) clones are frequently detected in patients with aplastic anaemia (AA). To evaluate the prognostic role of PNH clone presence we conducted a prospective study in 125 AA patients treated with combined immunosuppressive therapy (IST). Seventy‐four patients (59%) had a PNH clone (PNH+ patients) at diagnosis, with a median clone size of 0·60% in granulocytes and 0·15% in red blood cells. The response rate at 6 months was higher in PNH+ patients than that in PNH‐ patients, both after first‐ and second‐line IST: 68% vs. 45%, P = 0·0164 and 53% vs. 13%, P = 0·0502 respectively. Moreover, 42% of PNH+ patients achieved complete remission compared with only 16% of PNH‐ patients (P = 0·0029). In multivariate logistic regression analysis, PNH clone presence (odds ratio 2·56, P = 0·0180) and baseline absolute reticulocyte count (ARC) ≥30 × 10⁹/l (odds ratio 5·19, P = 0·0011) were independent predictors of response to treatment. Stratification according to PNH positivity and ARC ≥30 × 10⁹/l showed significant distinctions for cumulative incidence of response, overall and failure‐free survival. The results of this prospective study confirmed the favourable prognostic value of PNH clone presence in the setting of IST for AA.     

Anomalous Brownian motion discloses viscoelasticity in the ear's mechanoelectrical-transduction apparatus

The ear detects sounds so faint that they produce only atomic-scale displacements in the mechanoelectrical transducer, yet thermal noise causes fluctuations larger by an order of magnitude. Explaining how hearing can operate when the magnitude of the noise greatly exceeds that of the signal requires an understanding both of the transducer's micromechanics and of the associated noise. Using microrheology, we characterize the statistics of this noise; exploiting the fluctuation-dissipation theorem, we determine the associated micromechanics. The statistics reveal unusual Brownian motion in which the mean square displacement increases as a fractional power of time, indicating that the mechanisms governing energy dissipation are related to those of energy storage. This anomalous scaling contradicts the canonical model of mechanoelectrical transduction, but the results can be explained if the micromechanics incorporates viscoelasticity, a salient characteristic of biopolymers. We amend the canonical model and demonstrate several consequences of viscoelasticity for sensory coding.