Evaluation of the metabolism of PEP06,an endostatin-RGDRGD 30-amino-acid polypeptide and a promising novel drug for targeting tumor cells / 药物分析学报

PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEPO6 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.

SARS-CoV-2 testing among patients and healthcare professionals in an HIV outpatient clinic in Brazil

ABSTRACT The COVID-19 pandemic in Brazil has been marked by high infection and death rates. The immune response generated by current vaccination might be influenced by previous natural infection, and baseline estimates may help in the evaluation of vaccine-induced serological response. We evaluated previous SARS-CoV-2 testing (RT-PCR), and performed rapid diagnostic tests (RDT) and high throughput electrochemiluminescence immunoassay (ECLIA) before vaccination among people living with HIV (PLWH), users of antiretroviral prophylaxis (PrEP/PEP), and healthcare professionals in an HIV outpatient clinic (HCP-HC). RDT was positive in 25.7% (95% CI: 19-33%) overall, 31.3% (95% CI : 18-45%) among PLWH, 23.7% (95% CI : 14-34%) in PrEP/PEP users and 21.4% (95% CI : 05-28%) in HCP-HC (p=0.548). Diagnostic RT-PCR testing was very limited, even for symptomatic individuals, and whereas all HCP-HC had one test perfomed, only 35% of the patients (PREP/PEP/PLWH) were tested (p<0.0001). Adequate monitoring of post-vaccination humoral response and breakthrough infections including those in asymptomatic cases are warranted, especially in immunologically compromised individuals.

Efeitos agudos dos exercícios respiratórios, Threshold PEP™ e Powerbreathe® em pacientes com derrame pleural, no pós-procedimento de drenagem torácica / Acute effects of breathing exercises, Threshold PEP™ and Powerbreathe® in patients with pleural effect, in the post-thoracic drainage procedure

Introdução: O derrame pleural modifica as capacidades pulmonares, provocando distúrbio ventilatório restritivo. As terapias respiratórias evitam a progressão e tratam a restrição de volumes pulmonares. Objetivo: Comparar o efeito agudo de três recursos fisioterapêuticos em pacientes com derrame pleural após procedimento de drenagem torácica. Métodos: Estudo experimental, randomizado e prospectivo, realizado com 60 pacientes com derrame pleural, todos hospitalizados. A amostra foi dividida em 3 grupos com 20 pacientes, cada grupo recebeu uma terapia respiratória: exercícios respiratórios, Threshold PEP™ ou Powerbreathe®. Para avaliar a função pulmonar foram utilizados, a espirometria, a manovacuometria e o peak flow. Os atendimentos foram diários, seguiu-se o protocolo de 4 séries de 15 repetições. Análise estatística: aplicou-se os testes qui-quadrado de Pearson, Shapiro-Wilk, Friedman, Wilcoxon e correlação de Spearman. Para todos os testes considerou-se o nível de significância de 5%. Resultados: Os exercícios respiratórios resultaram em diferenças significativas na capacidade vital forçada (CVF), antes 1,66±0,60 e depois 1,84±0,50 (p=0,01), no volume expiratório forçado no primeiro segundo (VEF1), antes 1,25±0,46 e depois 1,57±0,52 (p=0,01), enquanto o grupo tratado com Threshold PEP™ a diferença significativa foi apenas na CVF, antes 1,49±0,78 e depois 1,78±0,85 (p=0,04). Em relação à força muscular respiratória, nenhuma das terapias resultou em diferença significativa na PImax e PEmax. Conclusão: O protocolo com exercícios respiratórios demonstrou superioridade na função pulmonar quando comparado com o Threshold PEP™ e Powerbreath®, tornando-se mais indicado no manejo de pacientes com derrame pleural após drenagem torácica.

HYD-PEP06 suppresses hepatocellular carcinoma metastasis, epithelial-mesenchymal transition and cancer stem cell-like properties by inhibiting PI3K/AKT and WNT/

HYD-PEP06, an endostatin-modified polypeptide, has been shown to produce effective anti-colorectal carcinoma effects through inhibiting epithelial-mesenchymal transition (EMT). However, whether HYD-PEP06 has similar suppressive effect on hepatocellular carcinoma (HCC) remained unknown. In this study, HYD-PEP06 inhibited metastasis and EMT but not proliferation

Knowledge and Practice of Post Exposure Prophylaxis among BDS Interns

Dental students face various threats during the time of their clinical training and learning, one of those is the possibility to be exposed to blood-borne infections, with the associated risk of HIV. According to UNAIDS, presently there are approximately 36.9 million people living with HIV/AIDS across the globe. The types of exposure which may pose risk to the dentist of acquiring blood-borne pathogens may be; percutaneous injury (e.g., Injury with needle-stick or with a sharp instrument), contact with the mucous membranes of the mouth or eye, contact with non-intact skin (e.g. chapped or abraded skin, or dermatitis affected skin). Methods: This was a cross sectional analytical study, conducted among Interns of various dental colleges of Lucknow, U.P. The study population of only 275 BDS interns voluntarily completed the questionnaire. A self-administrated questionnaire consisting of 14 close-ended items was used for data collection. The interns were given the questionnaire at the time of their clinical posting in various departments and were asked to fill it out without discussing it in fifteen minutes. Results: Total of 274 interns completed the survey. 83.2 % (n=228) interns heard about the term PEP. 93 % said that there should be guidelines regarding PEP in working areas, and 95% said that PEP can reduce the chances of developing AIDS in patients exposed accidentally to the used instrument/syringe. 53.3 % i.e. 146 interns had been pricked accidentally by infected instrument / Syringe. shockingly only 18 % interns went for the right way of PEP i.e. they first washed the prick area under running water, got the lab test of the patient and of self-done and by the time report comes they sought for medical advice and started the drug regimen. Conclusions: As this study as well as other studies in past have revealed that this is not rare for a dental practitioner to get pricked by any infected instrument or syringe during working on dental patients, the education of BDS students in Post Exposure Prophylaxis is mandatory which is not at all a part of BDS curriculum and thereby keeping dental graduates devoid of this life saving knowledge

Knowledge, attitude and practices about rabies prophylaxis among medical officers

Background: One of the important requirements to achieve “Zero Human rabies deaths by 2030” is to build awareness of the PEP and care for exposed victims. So, this study was undertaken with the aim and objective to study knowledge, attitude and practices related to animal bite transmitting rabies, amongst medical officer.Methods: A cross sectional study was done among 95 medical officer. Pretested and structured questionnaire was prepared related to training sessions conducted and their knowledge, attitude and practices (KAP) related to rabies prophylaxis. Data was entered and analysed using Microsoft Excel 16 version. Percentages were calculated and appropriate statistical test were applied.Results: None of them had received training on rabies prophylaxis. Regarding WHO categorization of animal bite, 69.5% participants had sufficient knowledge about category III, 47.4% about category II and 42.10% about Category I. Only 4.21% participants were aware of the preexposure prophylaxis and 29.47% participants had sufficient knowledge about intradermal (ID). schedule. Attitude was poor (47.40%) regarding willingness of administrating equine antirabies serum at their setup. 81% practiced immediate wound toileting and 45.30% of participants administered ARV by intradermal route. All patients were referred to tertiary care centre for administration of ARS and 82.10% of participants referred the patients immediately.Conclusions: There was an apparent lack of awareness seen in rabies prophalaxis and management. Effort should be taken to emphasize the importance PEP management through regular reorientation programs.

Research progress of nitrogen-terminal B-type natriuretic peptide and its clinical value in Kawasaki dis-ease / 国际儿科学杂志

Kawasaki disease ( KD) is an acute febrile illness that preferentially affects children youn-ger than 5 years old and the primary cause of acquired heart disease during childhood. Coronary artery aneu-rysms ( CAA) is a serious complication of KD, leading to ischemic heart disease, myocardial infarction, and sudden cardiac death. Timely initiation of treatment with intravenous immunoglobulin ( IVIG) has reduced the incidence of CAA from 25％ to 4％. Nitrogen-terminal B-type natriuretic peptide ( NT-proBNP ) , originally used for the management of adults with heart disease, was shown to be useful in the diagnosis and management of patients with KD. NT-proBNP is released by cardiomyocytes in response to mechanical factors, such as the dilation of cardiac chambers, and to pro-inflammatory cytokines. Patients with KD have higher NT-proBNP at the time of diagnosis than febrile controls. Moreover, patients with resistance to IVIG treatment and CAA were found to have higher levels of NT-proBNP, suggesting a prognostic role. This review summarizes the signifi-cance of NT-proBNP in the diagnostic value of KD in recent years.

Effect of PEP-1-SOD1 on Cell Apoptosis in SAP Rats / 胃肠病学

Background: Severe acute pancreatitis (SAP) is characterized by diffuse pancreatic hemorrhage and tissue necrosis with high mortality. PEP-1-SOD1 is a fusion protein synthesized by genetic engineering technology. It has a high stability and certain anti-inflammatory effects. Aims: To investigate the effect of PEP-1-SOD1 on cell apoptosis in SAP rats. Methods: A total of 24 male Wistar rats were divided into control group, SAP group and experimental group. SAP rat model was established by infusion of 5% sodium taurocholate. Thirty minutes before the establishment, rats in experimental group were abdominal subcutaneously injected with 8.0 mg/kg PEP-1-SOD1, and rats in SAP group were injected with same dose of 0.9% NaCl solution. Histopathological score of pancreatic tissue were evaluated; apoptosis of pancreatic acinar cell was determined by TUNEL. The mRNA and protein expressions of caspase-3 were detected by fluorescent quantitative PCR and Western blotting, respectively. Results: After 24 hours of model establishment, serum amylase and lipase, mRNA and protein expressions of caspase-3 in SAP group and experimental group were significantly higher than those in the control group (P<0.05), however, serum amylase and lipase in experimental group were significantly lower than those in SAP group (P<0.05), while mRNA and protein expressions of caspase-3 were significantly increased (P<0.05). After 6, 24 hours of model establishment, histopathological score, apoptotic index in SAP group and experimental group were significantly higher than those in the control group (P<0.05), however, histopathological score in experimental group was significantly lower than that in SAP group (P<0.05), while apoptotic index was significantly increased (P<0.05). Conclusions: PEP-1-SOD1 may increase the apoptosis of pancreatic acinar cells through regulating the expression of apoptosis related gene caspase-3 in SAP rats, thereby reducing the pathological damage of pancreatic tissue and promoting the recovery of pancreatic function.

Effects of orientin on cognitive function and hippocampus autophagy in APP/PS1 transgenic mice / 中国药理学通报

Aim To study the influence of orientin on the cognitive function in APP/PS1 double transgenic mice and the probable mechanisms. Methods The mice (7 months of age) were randomly assigned into three groups ( n = 8 in each group) ; non-transgenic mice (NT) and APP/PS1 transgenic mice (Tg) were given saline, and APP/PS1 transgenic mice with orientin ( Tg + Ori) , and were injected intraperitoneally once per day for 30 days. Morris water maze test was carried out for the evaluation of spatial learning and memory. The measurement of A|3 was conducted by immunohistochemical staining. Autophagy related protein expressions of LC3-II , p62, Cathepsin D and Be-clin-1 were measured by Western blot. Results Compared with NT group, Tg mice showed deficit memory formation, enhanced A(3 deposition and protein levels of LC3-H , p62 and Cathepsin D; compared with Tg group, Tg + Ori mice showed improved learning and memory, reduced A(3 load, and decreased levels of LC3-FJ ,p62 and Cathepsin D. The expression of Bec-lin-1 showed no difference between groups. Conclusions Orientin could improve the cognitive function, reduce amyloid plaques and ameliorate hippocampus autophagic clearance of APP/PS1 transgenic mice.

Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer

Recently, considerable attention in the field of cancer therapy has been focused on the mammalian rapamycin target (mTOR), inhibition of which could result in autophagic cell death (ACD). Though novel combination chemotherapy of autophagy inducers with chemotherapeutic agents is extensively investigated, nanomedicine-based combination therapy for ACD remains in infancy. In attempt to actively trigger ACD for synergistic chemotherapy, here we incorporated autophagy inducer rapamycin (RAP) into 7pep-modified PEG-DSPE polymer micelles (7pep-M-RAP) to specifically target and efficiently priming ACD of MCF-7 human breast cancer cells with high expression of transferrin receptor (TfR). Cytotoxic paclitaxel (PTX)-loaded micelle (7pep-M-PTX) was regarded as chemotherapeutic drug model. We discovered that with superior intracellular uptake and more tumor accumulation of micelles , 7pep-M-RAP exhibited excellent autophagy induction and synergistic antitumor efficacy with 7pep-M-PTX. Mechanism study further revealed that 7pep-M-RAP and 7pep-M-PTX used in combination provided enhanced efficacy through induction of both apoptosis- and mitochondria-associated autophagic cell death. Together, our findings suggested that the targeted excess autophagy may provide a rational strategy to improve therapeutic outcome of breast cancer, and simultaneous induction of ACD and apoptosis may be a promising anticancer modality.

Cutaneous manifestations of anti retroviral therapy used for post-exposure prophylaxis

Health care workers are at increased risk of needle stick injuries. Blood borne diseases that could be transmitted by such an injury include HIV, Hepatitis B, HCV and many others. Post exposure prophylaxis should be immediately started within 72 hours and should be continued for 28 days. Currently two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) are given along with one NNRTI (Non- Nucleoside reverse Transcriptase Inhibitor) including Efavirenz or Nevirapine. Multiple adverse effects have been reported with all the Anti- Retroviral Therapies including various cutaneous manifestations. A 22-year-old intern doctor studying in tertiary hospital of Ahmedabad had a needle stick injury with a needle contaminated with blood of HIV positive patient. Post Exposure prophylaxis was started within 72 hours consisting of fixed dose regimen of Tenofovir disprodoxil sulphate, Efavirenz and lamivudine. He was started with the drug within 2 hours and was prescribed one drug per day for next 27 days. On 22nd day he started having rash on his body which started on palms and soles. On 23rd day he saw severe facial edema along with edema on lips and rash spreading to other parts of the body. He was diagnosed with Hypersensitivity reaction and angioedema due to ART drug therapy. He was instructed to stop ART medications and was given antihistaminic for the symptoms. Patient's angioedema was relieved in 2-3 days and rash disappeared after 4-5 days. As he had already finished 23 days of therapy he was instructed to discontinue the drugs. No recurrence of rash or angioedema was noted. This case points out the severity of side effects in the normal healthy people taking ART as Post Exposure Prophylaxis. Apart from cutaneous manifestations, angioedema is a very grievous condition which doctors should always have lower threshold for diagnosis. Early diagnosis can prevent further complications. ART drugs have many complications and these patients should have intensive regular monitoring while on treatment. Also, proper education is required for needle cut injuries in health care workers.

The Adverse Effect of the 2-1-1 Regimen for Rabies PEP in Preschool Children / 生物医学与环境科学（英文）

Post-exposure prophylaxis (PEP) has proved to be the most important measure for rabies prevention and control. There is little information regarding adverse reactions to the Essen and 2-1-1 regimens in preschool children (aged 0-6). We reexamined the outcomes of 1,109 preschool children who were vaccinated using SPEEDA under the Essen regimen between January 2011 and December 2012 and 1,267 preschool children under the 2-1-1 regimen between January 2013 and December 2014. We find that, in preschool children, the febrile reaction after the first 2-dose injection in the 2-1-1 regimen was significantly higher than that induced by the first 1-dose in the Essen procedure. Thus, we recommend that the Essen regimen should still be used for rabies PEP in preschool children.

The Prevention and Management of Post-ERCP Pancreatitis / 대한췌담도학회지

Complications that may occur after an endoscopic retrograde cholangiopancreatography (ERCP) procedure include pancreatitis, bleeding, cholangitis, cholecystis, perforation, and post-ERCP pancreatitis (PEP). Of these, PEP is the most common complication and 10% of patients can die from severe pancreatitis. Prevention of PEP requires the selection of an appropriate patient group according to their ERCP indications and a full awareness of the risk factors. The incidence rate can be reduced to some extent through medication and ERCP manipulation changes. The use of a spile through the guidewire during ERCP manipulation and temporary pancreatic duct stent insertion can be effective, and the administration of suppository NSAIDs as medication reduces the occurrence of PEP. Drugs such as glyceryl trinitrate (GTN), nafamostat, and somatostatin can be considered as the second best treatment in the cases where NSAIDs are contraindicated or where a plastic catheter cannot be inserted or fails after insertion into the pancreatic duct.

Indomethacin preventing post-ERCP pancreatitis in patients aged under 50 years undergoing sEST combined with EPBD of choledocholithiasis / 中国生化药物杂志

Objective To study the effect of indomethacin preventing post-ERCP pancreatitis ( PEP ) on the patients younger than 50 years undergoing small endoscopic sphincterotomy (sEST) combined with endoscopic papillary balloon dilation(EPBD) in the treatment of choledocholithiasis. Methods 202 patients younger than 50 years with choledocholithiasis were divided into two groups, 101 patients in treatment group before surgery were rectal administrated with indometacin, 101 patients in control group were administered with placebo, all patients underwent sEST combined with EPBD in the treatment of choledocholithiasis.After operation,the abdominal pain NRS score, amylase, incidence of pancreatitis and hospitalization time were recorded, and the rates of heartburn, rash, gastrointestinal bleeding were recorded.Results In the treatment group, pain NRS score 24 hours after operation was(0.327 ±0.763), amylase 24 hours after operation was (116.87 ±113.97) U/L, there were 3 cases of postoperative pancreatitis (2.97%) in the treatment group,and the postoperative hospitalization time was (6.42 ±2.11) days.In the control group, pain NRS score 24 hours after operation was ( 0.634 ±1.027 ) , amylase 24 hours after operation was ( 185.38 ±160.60 ) U/L, there were 11 cases of postoperative pancreatitis (10.89%) in the control group, and the postoperative hospitalization time were (7.29 ±2.71) days.The differences of NRS pain score, amylase, incidence of pancreatitis, postoperative hospitalization time between these two groups were statistically significant ( P<0.05 ) .The differences of the rates of postoperative heartburn, rash, gastrointestinal bleeding between these two groups were not statistically significant.Conclusion Indomethacin rectal administration can prevent post-ERCP pancreatitis ( PEP ) on the patients who undergoing sEST combined with EPBD in the treatment of choledocholithiasis,and this administration is quite security.

Zero transmission of HIV: Till date’s only way leading towards its possible eradication.

Background: AIDS emerged as one of the most important public health issues of the late twentieth and early twenty-first centuries. The AIDS epidemic has prompted Wide-reaching changes in public health, clinical practice, and scientific research, and has had a great impact upon socities throughout the world. Aim: This article gave an insight into beak up of mode of transmission seen in our studied area of Gujarat, which highlighted in which area one should focus more at least to control the prevalence of HIV. Material and methods: In the present study 961 HIV sero-positive patients (T group) were screened with respiratory tract infections and more 300 HIV sero-positive patients but without respiratory tract infections (C2 group) had been inquired and collected their information about mode of transmission and other demographic characters like age, literacy, financial status, gender etc. Results: The highest patients had acquired HIV by hetro -sexual mode of transmission. In T group it was found to be in 773 (80.43%), while in C2 group it was seen among 257 (85.67%) HIV infected patients. But when both groups are merged which we consider TC2 group, this hetero-sexual mode of transmission was noted in 1030 (81.68%) HIV infected patients, followed by mother to child transmission (MTCT) which was found in 101 (10.51%) patients of T group while MTCT was seen in 29 (9.67%) HIV infected patients of C2 group. Conclusion: If anybody knows exact percentage of acquiring HIV in the particular area, one can work on this direction, to reduce that particularly mode mode of transmission seen in our studied area of Gujarat, which highlighted in which area one should focus more at least to control the prevalence of HIV. Material and methods: In the present study, 961 HIV sero-positive patients (T group) were screened with respiratory tract infections and more 300 HIV sero-positive patients but without respiratory tract infections (C2 group) had been inquired and collected their information about mode of transmission and other demographic like age, literacy, financial status, gender etc. Results: The highest patients had acquired HIV by hetero9-sexual mode of transmission. In T group it was found to be in 773 (80.43%), while in C2 group it was seen among 257 (85.67%) HIV infected patients. But when both groups are merged which we consider TC2 group, this hetero-sexual mode of transmission was noted in 1030 (81.68%) HIV infected patients, followed by mother to child transmission (MTCT) which was found in 101 (10.51%) patients of T group while MTCT was seen in 29 (9.67%) HIV infected patients of c2 group Conclusion: If anybody knows exact percentage of acquiring HIV in the particular area, one can work on this direction, to reduce that particular mode of transmission so that at least prevalence of HIV could certainly be decreased tremendously in that particular area, state, country and ultimately from globe. Minimum transmission of HIV can be achieved by widespread of ABC (Abstinence, behavioral change, condoms) policy and with additional maximum and quick implementation of TasP (Treatment as prevention), PrEP (Pre-exposure prophylaxis) and PEP (Post exposure prophylaxis) as and when required in the all ART Centres of our country.

Inhibitory effect of PEP-1-mediated recombinant hepatocyte nuclear factor 4 alpha transduction on hepatocellular carcinoma cells / 第二军医大学学报

Objective To investigate cell penetrating peptide (PEP-1)-mediated transduction of recombinant hepatocyte nuclear factor 4 alpha (HNF4α) protein into hepatocellular carcinoma (HCC) cells, and to observe the effect of the fusion protein P-HNF4α on HCC cells. Methods The expression vector pET28a-P-HNF4α was constructed. The prokaryotic expression condition of fusion protein P-HNF4α was optimized. Recombinant P-HNF4α carrying cell penetrating peptide PEP-1 was obtained by abundant expression, purified by affinity chromatography, and was concentrated and dialyzed. P-HNF4α was transduced into HCC cells. The transduction efficiency was analyzed by Western blotting analysis. Sub-cellular localization of P-HNF4α was detected by Western blotting analysis with nuclear and cytoplasmic extracts and confirmed by immunofluorescence assay. Real-time RT-PCR was used to examine the gene expression of HCC cells. The proliferation of HCC cells was detected with CCK-8 kit. The migration and invasion of HCC cells were detected by wound-healing assay and trans-well invasion assay, respectively. Results P-HNF4α was efficiently transduced into Huh7 cells and located in the nucleus as mediated by PEP-1. P-HNF4α significantly up-regulated the expression of characteristic hepatocyte markers and down-regulated the "stemness" genes in Huh7 cells (P<0.05 or P<0.01). Moreover, the proliferation (P<0.05), migration (P<0.001) and invasion (P<0.05) of HCC cells were significantly suppressed by fusion protein P-HNF4α. Conclusion P-HNF4α can induce the differentiation of HCC cells to mature hepatocytes and reduce the malignancy phenotype of HCC cells, suggesting that PEP-1-mediated HNF4α protein transduction may be a potential strategy for HCC differentiation therapy.

Changes of Pre Ejection Period and Left Ventricular Ejection Time during Head up Tilt.

Objective of the Study: Evaluate changes in Pre ejection period (PEP) and left ventricular ejection time (LVET) during head up tilt (HUT). Methods: Twenty healthy male subjects were involved in this study, with mean age 29.3±5 years, mean body mass index (BMI) 21.3±0.2Kg/m2. Measurement of PEP, LVET of Doppler wave form of the aortic flow were done at supine, 30 and 60 degree HUT. Measurement of HR and BP were done at these positions of tilting. Comparison of changes of these variables at different degrees of HUT was done by paired T-Test. Results: PEP values were significantly higher in 60 degree and 30 degree HUT than PEP values at supine position (p<0.0001). PEP values at 60 degree HUT were significantly higher than PEP values at 30 degree HUT (P=0.05). LVET values were significantly lower at 60 degree and 30 degree HUT than values at supine position (p<0.001), and LVET values were significantly lower at 60 degree HUT than values at 30 degree HUT (p<0.001). Conclusion: Key findings of PEP and LVET during HUT are progressive prolongation of PEP and shortening of LVET with increasing head up tilting.

Preparation of tumor-targeting chitosan micelle with transmembrane effect / 中国药科大学学报

Chitosan(CS)surface was modified with hydrophobic octyl groups to prepare N-octyl chitosan(nitro-gen-octyl chitosan;OC).Then hydrophilic group carboxyl-polyethylene glycol-amino (PEG);tumor-targeting lig-and D-glucosamine(DG);and membrane-penetrating peptide 9-D-arginine(9R)were linked to OC successively. Then the DG and 9R modified chitosan micelle (DG/9R-PEG-OC)with tumor-targeting and transmembrane effect was prepared.By hydrogen nuclear magnetic resonance spectrometer (1 H NMR)and sodium dodecyl sul-fate polyacryl amide gel electrophoresis(SDS-PAGE);the successful formation of DG/9R-PEG-OC was certified;with particle size of 151.8 nm and Zeta potential of 16.5 mV.The morphology of chitosan micelle observed by transmission electron microscope was homogeneous spherical structure.The drug loading content (DLC)(using fluorescein as a model drug)and encapsulation efficiency (EE)were about 28.2% and 75.0% measured by UV-visible spectrophotometer.Meanwhile;the drug showed a controlled releasing profile out of the micelle.Cellu-lar uptake experiments indicated DG/9 R-PEG-OC micelle had a significant tumor-tageting and transmembrane effects;especially on HepG2 cells;which exbihited high expression of the glucose transporter.Thus DG/9R-PEG-OC micelle could be a promising drug targeted delivery system of hydrophobic antitumor drugs.

Knowledge assessment about risk prevention of rabies amongst doctors in AIIMS, Jodhpur.

Background: Rabies still continues to be a public health problem in India and to protect our citizens from this menace; medical professionals have to be well equipped to tackle it more efficiently. The paper aims to assess the knowledge of residents and faculty in newly established AIIMS regarding risk prevention of rabies. Methods: A cross sectional study using a structured questionnaire on rabies was done at AIIMS Jodhpur amongst the doctors and the data was compiled in Microsoft excel 2010 were further analysed using SPSS version 21. Results: Out of the total sixty respondents, faculty constituted 38.3%, and junior residents and senior residents 28.3% and 33.3% respectively. Nearly 72% responded correctly regarding post exposure prophylaxis (PEP) i.e. 5 dose regimen of intramuscular administration of Anti Rabies Vaccine (ARV) and 56.7% doctors were unaware about the current recommendation of intradermal (ID) route. Rabies immunoglobulin (RIG) or Anti-Rabies Serum (ARS) against Rabies infection used in Class III bites was known to only 45% of the total doctors. Conclusion: The study reveals that there is a scope of improvement in important areas related to the knowledge of doctors in AIIMS regarding animal bites which needs to be upgraded time to time through continuing medical education in order to follow the standard protocol and guidelines at the apex institute.