Development of a recombinant vaccine against foot and mouth disease utilizing mutant attenuated Listeria ivanovii strain as a live vector.

The drawbacks of conventional inactivated Foot and Mouth Disease (FMD) vaccine, such as escaping of the virus during manufacture processes prompted researchers to explore novel types of vaccine to overcome these disadvantages. Listeria ivanovii (LI) is an intracellular microorganism that possesses immune-stimulatory properties, making it appropriate for use as a live bacterial vaccine vector. The Foot and mouth disease virus (FMDV) VP1 protein is the most immunogenic part of FMDV capsid, it has most of the antigenic sites for viral neutralization. The expression of antigen gene cassette in vitro was confirmed by Western blot analysis. Mice were able to eliminate LI△actAplcB-vp1 from the liver and spleen within few days revealed a safety of the candidate vaccine. Two doses of LI△actAplcB-vp1 with 14 days of interval were injected into mice. High levels of specific IgG antibodies and CD8+ and CD4+ T cells secreted cytokines including IFN-γ, TNF-α and IL-2 against FMDV-VP1 were achieved. Based on the obtained results, LI△actAplcB-vp1 candidate vaccine utilizing Listeria ivanovii as a live vector-based vaccine could enhance a specific cellular and humoral immune responses against the inserted FMDV-vp1 heterologous genes. LI△actAplcB-vp1 candidate vaccine could be a modern tool to overcome the disadvantages of the traditional inactivated FMD vaccine.

Expression of the VP1 protein of FMDV integrated chromosomally with mutant Listeria monocytogenes strain induced both humoral and cellular immune responses.

Live vector-based vaccine is a modern approach to overcome the drawbacks of inactivated foot-and-mouth disease (FMD) vaccines such as improper inactivation during manufacture. Listeria monocytogenes (LM), an intracellular microorganism with immune-stimulatory properties, is appropriate to be utilized as a live bacterial vaccine vector. FMDV-VP1 protein has the capability to induce both cellular and humoral immune responses since it is considered the most immunogenic part of FMDV capsid and has the most of antigenic sites for viral neutralization. The codon-optimized vp1 gene was ligated to the integrative pCW702 plasmid to construct the target cassette. The antigen cassette was integrated successfully into the chromosome of mutant LM strain via homologous recombination for more stability to generate a candidate vaccine strain LM△actAplcB-vp1. Safety evaluation of recombinant LM△actAplcB-vp1 revealed it could be eliminated from the internal organs within 3 days as a safe candidate vaccine. Mice groups were immunized I.V. twice with the recombinant LM△actAplcB-vp1 at an interval of 2 weeks. Antigen-specific IgG antibodies and the level of CD4+- and CD8+-specific secreted cytokines were estimated to evaluate the immunogenicity of the candidate vaccine. The rapid onset immune response was detected, strong IgG humoral immune response within 14 days post immunization and augmented again after the booster dose. Cellular immunity data after 9 days post the prime dose indicated elevation in CD4+ and CD8+ secreted cytokine level with another elevation after the booster dose. This is the first report to explain the ability of attenuated mutant LM to be a promising live vector for FMDV vaccine.

Intensive Care Unit Physician's Attitudes on Do Not Resuscitate Order in Palestine.

BACKGROUND: There is some ambiguity concerning the do-not-resuscitate (DNR) orders in the Arabic world. DNR is an order written by a doctor, approved by the patient or patient surrogate, which instructs health care providers to not do CPR when cardiac or respiratory arrest occurs. Therefore, this research study investigated the attitudes of Intensive Care Unit physicians and nurses on DNR order in Palestine. MATERIALS AND METHODS: A total of 123 males and females from four different hospitals voluntarily participated in this study by signing a consent form; which was approved by the Ethical Committee at Birzeit University and the Ministry of Health. A non-experimental, quantitative, descriptive, and co-relational method was used, the data collection was done by a three page form consisting of the consent form, demographical data, and 24 item-based questionnaire based on a 5-point-Likert scale from strongly agree (score 1) to strongly disagree (score 5). RESULTS: The Statistical Package for Social Sciences (SPSS) software program version 17.0 was used to analyze the data. Finding showed no significant relationship between culture and opinion regarding the DNR order, but religion did. There was statistical significance difference between the physicians' and nurses' religious beliefs, but there was no correlation. Moreover, a total of 79 (64.3%) physicians and nurses agreed with legalizing the DNR order in Palestine. CONCLUSION: There was a positive attitude towards the legalization of the DNR order in Palestine, and culture and religion did not have any affect towards their attitudes regarding the legalization in Palestine.

Prevalence of HLA-B27 in Patients with Ankylosing Spondylitis in Qatar.

Background and Objectives. The human leukocyte antigen HLA-B27 is a class 1 antigen of the major histocompatibility complex and is strongly associated with ankylosing spondylitis (AS). The purpose of the present study is to investigate the distribution of HLA-B27 in patients with AS of different ethnic groups in Qatar. Design and Setting. Study design was cross-sectional and the setting was rheumatology clinics of Hamad General Hospital in Qatar where most of ankylosing spondylitis patients are followed up. Patients and Methods. Patients with diagnosis of AS who met the New York modified criteria for AS were tested for HLA-B27. 119 patients were tested for HLA-B27: 66 Arabs, 52 Asians (Indians, Pakistanis, Bengalis, and Iranians), and one Western (Irish). Results. Of all the individuals, 82 were positive (69%) for HLA-B27. Among the Arabs, 49/66 were positive (74%). Among the Asians, 32/52 were positive (61%). Furthermore, Qatari patients (10 males and one female) 9 were positive (82%), 14/19 Jordanians/Palestinians were positive, and 9/10 (90%) Egyptians were positive. Among the Asians, 19/26 Indians were positive (73%), which was similar to the Arabs. Conclusion. HLA-B27 in our small group of Arabs is present in 74%. Comparison with other data will be presented in detail.

The impact of intraoperative transoesophageal echocardiography on decision-making during cardiac surgery.

BACKGROUND: Real time intraoperative transoesophageal echocardiograpgy (TOE) has an expanding role in peri-operative management and surgical decision making. OBJECTIVES: Studies of the effect of transoesophageal echocardiography (TOE) on intraoperative decision making commonly emphasise major changes in operative plans. We examined more subtle effects using a novel scale, recording influences on management as follows: Level 1: TOE had no effect on management, confirmed and quantified known pathology. Level 2: TOE altered hemodynamic and/or anesthetic management. Level 3: TOE evaluated the adequacy of surgical intervention/or repair. Level 4: TOE led to an alteration in the surgical plan. We compared the impact of TOE as an aid to intra-operative management in coronary artery bypass cases with other types of cardiac surgery. METHODS: Retrospective, observational study in a single centre, university-affiliated hospital included 319 patients undergoing cardiac surgery and suitable for TOE. TOE was performed in each patient before and after the institution of cardiopulmonary by-pass. Normal and abnormal echocardiographic findings as well as immediate outcomes of the surgical procedure were recorded using a standard database form. Instances where TOE lead to alteration in operative management were documented. The findings were also compared with those documented on preoperative echocardiography. RESULTS: In 141 CABG patients TOE had a level 1 impact in 73%, level 2 impact in 11.6%, levels 3 and 4 in 7% and 7.8% respectively. In 178 non CABG patients these values were 2%, 1.6%, (p < 0.05), 72.4% (p < 0.05) and 23.6% (p < 0.05) respectively. CONCLUSION: The impact of TOE in CABG procedures, while significantly less than that in non-CABG surgical procedures, remains substantial.

Antinociceptive and anti-inflammatory activity of a novel quipazine derivative (AAL-13): a selective inhibitor of 5-hydroxytryptamine reuptake.

The anti-inflammatory and antinociceptive activities of a novel quipazine derivative 2(4-(3-chloropropyl)piperazinyl) quinoline (AAL-13), a selective inhibitor of 5-hydroxytryptamine (5-HT) reuptake, has been examined. Anti-inflammatory activity was assessed by mesuring the inhibition of a cotton pellet granuloma and of carrageenan-induced paw oedema in rats, and of cantharidin-induced topical inflammation in the mouse ear. Antinociceptive activity was studied by using the modified Randall-Selitto method. Indomethacin was used as a reference. AAL-13 slightly inhibited granuloma formation (13%, P less than 0.02) at 100 mg kg-1 day-1 for 7 days, whereas half that dose had no significant effect. There was significant inhibition of carrageenan-induced rat paw oedema (35%, P less than 0.05 and 103%, P less than 0.001) 3 h after single doses of AAL-13 (50 and 100 mg kg-1 p.o., respectively). Three hours after i.p. injection, the oedema inhibition was 58% (P less than 0.05) and 86% (P less than 0.001) for doses of 25 and 50 mg kg-1, respectively. In comparison, indomethacin (3, 6 and 12 mg kg-1 p.o.) inhibited oedema by 59% (P less than 0.02), 65% (P less than 0.01) and 63% (P less than 0.02), respectively. Intraperitoneally, only the 12 mg kg-1 dose produced significant inhibition (82%, 3 h after carrageenan injection, P less than 0.05). AAL-13 (1.5 mg/ear) had a significant anti-inflammatory effect on the mouse ear (52%, inhibition, P less than 0.05), while indomethacin (3 mg/ear) gave 43% inhibition (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

5-Hydroxytryptamine (serotonin) enhances ventricular arrhythmias induced by acute coronary artery ligation in rats.

Ventricular arrhythmias were induced by acute coronary artery ligation in anesthetized rats. 5-Hydroxytryptamine (5-HT) in doses of 100-200 micrograms kg-1, given i.v. 5 minutes before coronary artery ligation, enhanced the severity of ventricular arrhythmias as shown by a significant dose-dependent increase in the number of ventricular ectopic beats, duration of ventricular tachycardia (VT) and ventricular fibrillation (VF). This effect was antagonized by pretreatment with the selective 5-HT2-receptor antagonist ritanserin (1 mg kg-1, i.p.) given 15 minutes before 5-HT. Ritanserin when used alone was observed to produce a significant reduction in the number of ventricular ectopic beats and duration of VT and VF. 5-HT significantly lowered the heart rate and produced initial rise of the systolic blood pressure (SBP). These effects were antagonized by ritanserin. Ritanserin significantly lowered the heart rate but did not alter the SBP. It was postulated that 5-HT might be implicated in the genesis and determination of severity of ventricular arrhythmias induced by acute myocardial ischemia, and that this effect is mediated via 5-HT2-receptors. 5-HT2-receptor antagonists may provide potential useful therapeutic agents for the management of these arrhythmias.

Suppression of ventricular arrhythmias resulting from acute coronary artery ligation in rat by imipramine.

The potential antiarrhythmic activity of imipramine against ventricular arrhythmias induced by coronary artery ligation in rats has been investigated and compared with procainamide. Imipramide (1 and 5 mg/kg-1) or procainamide (5 and 10 mg/kg-1) or solvent were injected intravenously 30 min before ligation. Imipramine reduced the total number of ventricular ectopic beats as well as the incidence and duration of ventricular tachycardia and ventricular fibrillation. The drug did not significantly affect the blood pressure but reduced the heart rate. The antiarrhythmic activity of imipramine is postulated to be due to a quinidine-like effect and/or alpha-adrenergic blocking activity. The study confirms the potential utility of imipramine as an antiarrhythmic drug.

Performance of men and women medical students at King Saud University, Riyadh: a 10-year retrospective study.

This study was carried out using the results of medical students at the College of Medicine at King Saud University, Riyadh between 1975 and 1985. The purpose of the study was to ascertain whether any correlation existed between school performance and college performance, whether results from males were different from results from females, and whether the semester system, in operation since 1981, produced different results from the annual system. Significant correlations were found between school Grade Point Average (GPA) results and college results, being highest for premedical courses and lowest for clinical courses. However, these correlations were too small to be of practical use. Men students were found to perform better at preclinical subjects whereas women had better results at clinical subjects. The overall performance on the semester system was significantly higher than that on the annual system.