Effects of PAMAM dendrimers in the mouse brain after a single intranasal instillation

Dendrimers are highly branched spherical nanomaterials produced for use in diagnostic and therapeutic applications such as a drug delivery system. The toxicological profiles of dendrimers are largely unknown. We investigated the in vivo effects of nasal exposure to polyamidoamine (PAMAM) dendrimers on their effects on neurological biomarkers in the mouse brain. A single dose of PAMAM dendrimers (3 or 15 μg/mouse) was intranasally administered to 8-week old male BALB/c mice. Twenty-four hours after administration, the olfactory bulb, hippocampus, and cerebral cortex were collected and potential biomarkers in the blood and brain were examined using blood marker, microarray and real-time RT-PCR analyses. No remarkable changes in standard serum biochemical markers were observed in the blood. A microarray analysis showed the alterations of the genes expression level related to pluripotent network, serotonin-anxiety pathway, TGF-beta receptor signaling, prostaglandin synthesis-regulation, complement-coagulation cascades, and chemokine-signaling pathway and non-odorant GPCR signaling pathways in brain tissues. Brain derived-neurotrophic factor mRNA was up-regulated in the hippocampus and cerebral cortex in mice treated with a high dose of dendrimers. These findings suggest that PAMAM dendrimers may reach the brain via the systemic circulation or an olfactory nerve route after intranasal instillation, and indicate that a single intranasal administration of PAMAM dendrimers may potentially lead to neuronal effects by modulating the gene expression of brain-derived neurotrophic factor signaling pathway.     

Preferred CDRH3 lengths for antibodies with defined specificities [In Process Citation]

The third complementarity determining regions of heavy chain variable regions (CDRH3) confer the fine specificities of antibodies. The CDRH3 length distribution of all human or all mouse antibodies appears to be more or less random, with the human distribution having a wider spread. Since the Kabat database of aligned amino and nucleotide sequences of proteins of immunological interest has grown at least 4 times during the past 7 years, we attempt to study CDRH3 length distributions of human and mouse antibodies with defined specificities, where enough complete and distinct CDRH3 sequences are available. For mouse antibodies against small haptens or carbohydrates, a preferred length usually dominates for a given specificity. There are not enough human sequences of small hapten or carbohydrate antibodies for a similar study. Both human and mouse anti-protein antibodies have wider ranges of CDRH3 length distributions, probably due to the presence of different antigenic epitopes on the protein molecules, and thus many different antibodies. For anti-DNA antibodies, both humans and mice exhibit even wider length distributions, since DNA can be double stranded, single stranded, supercoiled, etc.      

Making Scents: Improvement of Olfactory Profile after Botulinum Toxin-A Treatment in Healthy Individuals

BACKGROUND The axilla is particularly associated with body odor and putative pheromone production in humans. Although botulinum toxin type A (BT-A) is injected increasingly into the axillary skin to stop excessive sweating, its potential to control body odor is largely unexplored.
OBJECTIVE The objective was to measure the impact of BT-A on human axillary odor in an objective and reproducible fashion.
METHODS This study was a randomized, double-blind, placebo-controlled trial with 51 healthy volunteers receiving 50 U of BOTOX (Allergan, Inc.) in one axilla and placebo in the other. Odor quality was assessed by treated subjects (questionnaire) as well as by independent raters who were exposed to blinded T-shirt samples.
RESULTS No major side effects occurred, and no subject withdrew from the study for medical reasons. Samples from the BT-A–treated side smelled less intense ( p <.001) and better ( p <.001) according to self-assessments. Likewise, independent raters found the BT-A–treated samples to smell less intense and better ( p <.001). They preferred "to work together with the respective person" and found the odor "more erotic" ( p <.001).
CONCLUSION Side-by-side comparison of odor samples (T-shirt sniff test) by independent raters showed that axillary odor in healthy individuals is significantly more appealing after BT-A injection.     

Predictors and survival in hepatitis B-related hepatocellular carcinoma in New South Wales, Australia

Background and Aim: Incidence and mortality of hepatocellular carcinoma (HCC) has increased markedly over the last three decades in Australia. An increasing proportion of HCC cases is related to chronic viral hepatitis including hepatitis B virus (HBV) infection. However, there is very limited data on HBV‐related HCC survival. Methods: Data on HBV‐related HCC cases was obtained from a community‐based linkage study. HCC cases notified to the New South Wales (NSW) Central Cancer Registry (CCR) during the period 1994–2002 were linked to HBV notifications from the NSW Health Department. Age, sex, country of birth, year of diagnosis, tumor stage were extracted from the CCR database. Survival analysis was conducted to determine median survival and identify predictors of survival. Results: Over the 9‐year study period, 278 HCC cases were linked to chronic HBV infection. The majority of cases were male (83.5%) and overseas‐born (93.6%); Asian‐born cases accounted for 72.1%. Median survival following HCC diagnosis was 15.0 months. HCC survival was poorer among older age groups (P < 0.0001), and among cases with regional spread (hazard ratio, 3.23; 95% confidence interval, 1.83–5.69; P < 0.0001) and distant metastases (hazard ratio, 3.85; 95% confidence interval, 2.44–6.08; P < 0.0001). Sex, region of birth and study period (1994–1997 vs 1998–2002) were not associated with HCC survival. Conclusion: The vast majority of HBV‐related HCC were overseas‐born, however, region of birth was unrelated to HCC survival. The continued extremely poor HCC survival, including lack of improvement in HCC survival in more recent years, suggests low uptake of HCC screening programs. Public health strategies including early diagnosis and appropriate referral for antiviral therapy assessment and increased HCC screening among high‐risk populations are required to reduce HCC incidence and improve HCC survival.     

Dengue as a cause of acute undifferentiated fever in Vietnam

Background  

Dengue is a common cause of fever in the tropics but its contribution to the total burden of febrile illnesses that is presented to primary health facilities in endemic regions such as Vietnam, is largely unknown. We aimed to report the frequency of dengue as a cause of fever in Binh Thuan Province, to describe the characteristics of dengue patients, and analyze the diagnostic accuracy of the health care workers and the determinants of the diagnostic process.     

The predictors of red cell transfusions in total hip arthroplasties

BACKGROUND: Most blood crossmatched in a hospital blood bank is for surgical patients, and the majority is never transfused. The maximal standard blood order schedule is used to promote efficient ordering practices for surgical patients. STUDY DESIGN and METHODS: To ascertain the predictors of red cell transfusions for patients undergoing total hip arthroplasty, the charts of 299 adult patients undergoing primary and revision total hip arthroplasty were reviewed. A surgical blood order equation was developed for calculating the number of units of red cells that should be ordered. Stepwise regression analysis was used to determine which patient-and-case-related variables should be considered in the surgical blood order equation. RESULTS: The significant indicators for allogeneic red cell transfusion to patients on the day of total hip arthroplasty were preoperative hemoglobin concentration, weight, age, estimated blood loss, and aspirin use. The surgical blood order equation would result in a lower crossmatch-to-transfusion ratio than would the maximal standard blood order schedule (1.23 vs. 3.14). Costs were also lower with the surgical blood order equation. CONCLUSION: Incorporation of patient factors resulted in increased efficiency of blood-ordering practices in total hip arthroplasty.     

老年充血性心力衰竭患者血浆脑钠肽前体水平与长期预后的关系

目的:血浆脑钠肽水平对于充血性心力衰竭的预后评估均具有重要意义,但脑钠肽前体的敏感性和特异性更高。分析血浆脑钠肽前体水平对老年充血性心力衰竭患者长期预后的预测价值。方法:选择2003-05/2005-07在桂林医学院附属医院心内科住院的心力衰竭患者208例及本科同期收住院的急性冠状动脉综合征组患者26例,另外选择正常对照组30例,为本院的医学生,以上观察对象均自愿参加观察。分别测定各组观察对象的血浆脑钠肽前体水平,均在入院的第1天完成,患者出院后不再测定脑钠肽前体。使用惠普500型心动图检测心力衰竭组患者的心脏各腔室直径及射血指数。对所有出院的心力衰竭患者均进行电话随访,每3个月随访1次,平均随访2年,只电话询问死亡还是健在。结果:心力衰竭患者208例、急性冠状动脉综合征患者26例及正常对照组30例全部进入结果分析,无脱落。①各组观察对象的血浆脑钠肽前体水平比较:心力衰竭组是正常对照组的150倍[(4.82±0.75)μg/L,(31.38±29.28)ng/L(P<0.01)],是急性冠脉综合征组的23倍[(208.80±120.13)ng/L(P<0.01)]。②不同年龄、性别、病种、心功能分级心力衰竭患者血浆脑钠肽前体水平比较:心力衰竭患者脑钠肽前体的水平随年龄的增加而升高(P<0.05～0.01);女性显著高于男性(P<0.01);心功能不同级别间脑钠肽前体的水平呈倍数增加(P<0.01),死亡者显著高于生存者(P<0.01)。③心力衰竭患者血浆脑钠肽前体水平与各临床指标的相关性分析:心力衰竭患者血浆脑钠肽前体水平与年龄、左心室直径及纽约心脏协会心功能分级呈正相关(r=0.310,0.283,0.647,P<0.05～0.01),与射血指数呈负相关(r=-0.327,P<0.01)。结论:老年心力衰竭患者的血浆脑钠肽前体水平明显增高,与之相关的预后不良危险因素包括心功能分级增高、射血分数降低、左心室直径扩大、老年及女性心力衰竭患者等。     

Superoxide generation and cytotactic response of irradiated neutrophils

Irradiation of blood components has been used to prevent transfusion-related graft-versus-host disease (GVHD) in immunocompromised patients. This study was designed to determine the effect of irradiation on neutrophil aggregation, chemotaxis, and superoxide generation. Purified neutrophils were irradiated with a Cesium source at four doses ranging from 0 to 17,500 rads. Formyl-methionyl-leucyl-phenylalanine (FMLP) and zymosan-treated serum (ZTS) cytotaxin-induced chemotaxis and migration were determined in the agarose assay. Neutrophil aggregation to FMLP was determined by aggregometry. Superoxide generation and random migration were not affected by irradiation at doses up to 17,500 rads. When compared to nonirradiated controls, the chemotactic response to ZTS remained normal, with an insignificant decline from 174 +/- 31.0 to 150 +/- 42.3 (mean +/- SD) units. The chemotactic response to FMLP declined insignificantly, from 228 +/- 31.3 at 0 rad to 207 +/- 26.4 at 17,500 rads. The aggregation response to FMLP remained within the normal range but declined from 0.78 +/- 0.11 to 0.61 +/- 0.18. At the radiation doses currently used to reduce the risk of transfusion-related GVHD, neutrophil superoxide generation and chemotactic response remain essentially normal.