Subcutaneous immunization with a novel immunogenic candidate (urease) confers protection against Brucella abortus and Brucella melitensis infections

Brucellosis is a world prevalent endemic illness that is transmitted from domestic animals to humans. Brucella spp. exploits urease for survival in the harsh conditions of stomach during the gastrointestinal infection. In this study, we examined the immune response and the protection elicited by using recombinant Brucella urease (rUrease) vaccination in BALB/c mice. The urease gene was cloned in pET28a and the resulting recombinant protein was employed as subunit vaccine. Recombinant protein was administered subcutaneously and intraperitoneally. Dosage reduction was observed with subcutaneous (SC) vaccination when compared with intraperitoneal (IP) vaccination. rUrease induced mixed Th1–Th2 immune responses with high titers of specific IgG1 and IgG2a. In lymphocyte proliferation assay, splenocytes from IP and SC‐vaccinated mice displayed a strong recall proliferative response with high amounts of IL‐4, IL‐12 and IFN‐γ production. Vaccinated mice were challenged with virulent Brucella melitensis, B. abortus and B. suis. The SC vaccination route exhibited a higher degree of protection than IP vaccination (p value ≤ 0.05). Altogether, our results indicated that rUrease could be a useful antigen candidate for the development of subunit vaccines against brucellosis.     

Schizophrenia following new-onset refractory status epilepticus secondary to antiphospholipid syndrome

New-onset refractory status epilepticus (NORSE) is a drug-resistant status epilepticus that often has a catastrophic outcome. Our patient was diagnosed with NORSE and had an EEG reading that showed status epilepticus persisting for 8 months in general anesthesia. After autoimmune workup showed positive antiphospholipid antibodies, his seizure was controlled, and he was discharged with good condition apart from moderate cognitive impairment. However, he later developed schizophrenia. Although psychiatric disorders have been associated with antiphospholipid syndrome, to the best of our knowledge, it has not been reported to be associated with status epilepticus. We recommend vigilance of psychological complications of refractory status epilepticus’ patients for early psychiatric referral, diagnosis, and treatment.

New-onset refractory status epilepticus (NORSE) is a syndrome of new-onset drug-resistant status epilepticus that often has a catastrophic outcome. Epilepsy is usually associated with psychiatric disorders of different manifestations of which psychosis is an example.1 However, not much is found in the literature review regarding psychiatric disorders following NORSE although a recent study concluded 32% of NORSE patients ended up with altered behavioral states like aggression.2 Schizophrenia following NORSE like in the rare presentation of this case has not been reported in the literature review before, although an association between schizophrenia and autoimmune disorders like APS has been reported.3     

N-acetylcysteine does not modify nitroglycerin-induced tolerance in canine vascular rings

The mechanism whereby nitroglycerin initiates relaxation in vascular smooth muscle remains unclear. One hypothesis states that nitroglycerin oxidizes critical sulfhydryl groups in smooth muscle to initiate relaxation, and that repeated exposure to nitroglycerin results in tolerance. In the current study, N-acetylcysteine, a sulfhydryl-reducing agent, was used to explore the sulfhydryl hypothesis by assessing whether or not tolerance to nitroglycerin was reversed by N-acetylcysteine in canine dorsal pedal artery rings. Two nitroglycerin dose-response curves were performed (n = 18)--one before (1st dose-response curve, from 10(-9) to 1.1 X 10(-5) M nitroglycerin) and one after (2nd dose-response curve, from 10(-9) to 5 X 10(-7) M nitroglycerin) incubation with 10(-5) M nitroglycerin for 105 min. At 5 X 10(-7) M nitroglycerin there was 50.7 +/- 10.0% relaxation during the first dose-response curve. During the second dose-response curve, tolerance to nitroglycerin was evident, as demonstrated by a 6.8 +/- 4.8% relaxation (p less than 0.001) at 5 X 10(-7) M nitroglycerin. A 10-min treatment with 10(-3) M N-acetylcysteine (n = 10) during the second nitroglycerin dose-response curve was performed after the 5 X 10(-7) M concentration of nitroglycerin; the second dose-response curve was then completed up to 1.1 X 10(-5) M nitroglycerin. The dose of 10(-3) M N-acetylcysteine was chosen since higher concentrations (i.e., 1.3 X 10(-2) and 1.2 X 10(-1) M N-acetylcysteine) produced 20.3 +/- 8.4 and 43.6 +/- 11.6% relaxation in vascular rings (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)     

Buprenorphine pharmacokinetic parameters during coronary artery bypass graft surgery

The pharmacokinetic parameters of buprenorphine (BN) after a single bolus dose of 10 microg/kg i.v. was investigated in 6 male patients whose age averaged 59+/-9.8 years and body weight of 65.8+/-5.7 kg undergoing coronary artery bypass graft surgery (CABG). The unbound BN plasma concentrations were detected using ultrafiltration and high performance liquid chromatography/electro-chemical detection (HPLC/ECD) method. During cardiopulmonary bypass (CPB) there was a fall in BN plasma concentrations, observations similar to reports on fentanyl, sufentanil and alfentanil. This is probably due to haemodilution, hypothermia and hydrophobic sequestration of drug on to the CPB tubing. After CPB the concentrations rose to values higher than during CPB, though it did not attain pre CPB concentrations. These variations were not statistically significant indicating that plasma levels were adequately stable during CPB. The plasma concentration time curves were biexponential and the pharmacokinetic parameters obtained were : distribution half-life 37.24+/-6.57 min, elimination half-life 482.69+/-79 min, clearance 1221.97+/-209.42 ml/min, and volume of distribution 736.46+/-71.25 L. BN in the dose used follows the pharmacokinetic pattern of other commonly used narcotics during CABG. The mean +/- SEM plasma BN concentration during CPB was 0.51+/-0.03 ng/ml which was adequate for the maintenance of analgesia and anaesthesia, as none of our patients expressed the signs and symptoms of awareness during surgery. Further, unlike the other narcotics muscle rigidity was absent. Thus BN is a safe and good alternative to other narcotics for patients undergoing CABG.     

The potential use of toll-like receptor (TLR) agonists and antagonists as prophylactic and/or therapeutic agents

Toll-like receptors (TLR) and their ligands are one of the main players in the initiation of innate immunity which precedes, and is required, for the establishment of adaptive immunity. Manipulating the immune response by using TLR agonists or antagonists might be of therapeutic and/or prophylactic value. This review covers; 1-TLR. their natural ligands and ligand - TLR signaling events, 2-TLR againsts and their use in clinical trials as vaccine adjuvants, and to treat allergy, cancer and infectious diseases, 3-TLR antagonists and their use in clinical trials to treat septic shock and autoimmune diseases. Potential drawbacks related to their potential use as prophylactic and/or therapeutic agents are discussed.     

The utilization of Arabic online drug information among adults in Saudi Arabia

In Saudi Arabia, the utilization of the world wide web has become increasingly popular. However, the exact figure of such use is unknown. This study aimed to determine the percentage of, and experience with, online Arabic drug information by Arabic-speaking adults in Saudi Arabia. A web based questionnaire was used. The questionnaire language was Arabic. Public were invited to participate in the survey through e-mails, Twitter, WhatsApp and Facebook in March 2012. The survey included 17 items examining the types of accessed Arabic drug information, the respondent’s demographics, their ability to easily find and understand Arabic drug-related information, and their trustfulness and dependency on such information websites. Of the 422 Arabic speaking adults who answered the questionnaire, 88% stated that they used Arabic websites to answer drug-related questions. Of the respondents, 50% had a bachelor’s degree, 44% were young adults, over half were female (60%), and 72% of them have a chronic disease. The ease of retrieving online information was the most common reason (69%) for consulting such websites. Google as a search engine was the most frequently (86%) accessible website. Although respondents reported different drug-related topics in their online searching, the search for adverse effects was the most common (68%). Respondents claimed that they could easily find (65%) and understand (49%) the drug-related information. Although a good number of respondents qualified this type of information as good, double-checking of information on other websites was highly recommended. Trustfulness was one of the important parameters to measure and 205 respondents (55%) claimed that they only trusted half of the information cited. Moreover, around 48% of respondents considered that finding the same information on more than one website increased its trustfulness. Surprisingly, 54% of respondents did not depend on Arabic information websites when making decisions on drug use. There are a high proportion of Arabic speaking people in Saudi Arabia using and consulting Arabic drug information websites. This information is easily found and understood. However, the quality and trustfulness of such websites are not high enough to depend on them. A qualified Arabic drug information website is important to meet this need.     

Comparison of silver nylon wound dressing and silver sulfadiazine in partial burn wound therapy

The study aims to perform a comparative assessment of two types of burn wound treatment. To do the assessment, patients with partial thickness burn wounds with total body surface area <40% were simple randomised to treat with nanocrystalline silver nylon wound dressing or silver sulfadiazine cream. Efficacy of treatment, use of analgesics, number of wound dressing change, wound infection and final hospitalisation cost were evaluated. The study showed silver nylon wound dressing significantly reduced length of hospital stay, analgesic use, wound infection and inflammation compared with silver sulfadiazine.     

Potential of two nucleic acid amplification assays for quantifying mycobacterial load in respiratory and non-respiratory specimens: a prospective study

Quantification of bacillary load plays a critical prognostic role in tuberculosis patients. This study evaluated the potential of the Cepheid GeneXpert (GX) MTB/RIF and the BD ProbeTec system as quantitative assays. The time to positivity (TTP) measured by the Mycobacterial Growth Index Tube system was compared to the cycle threshold (C_t) of GX MTB/RIF and the Metric Other than Acceleration (MOTA) scores generated by the ProbeTec system. Out of 714 samples examined, 44 culture confirmed cases were identified. The C_t values in 21 respiratory samples showed a high linear fit with the TTP in liquid culture (Spearman's correlation coefficient r = 0.9, P value < 0.0001), which was not the case in 23 non-respiratory samples. In both types of specimens, the MOTA scores did not correlate with the TTP in liquid culture. This indicates the suitability of GX as a quantitative measurement of mycobacterial load in respiratory but not non-respiratory specimens.