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     

High throughput tissue microarray analysis of FHIT expression in diffuse large cell B-cell lymphoma from Saudi Arabia.

Recent studies have suggested a potential prognostic role of alterations of the fragile histidine triad (FHIT) gene in diffuse large B-cell lymphoma. To evaluate possible mechanisms of FHIT inactivation and to further clarify its potential prognostic relevance, we analyzed a set of 114 diffuse large B-cell lymphoma with clinical follow-up information. Tissue microarrays were analyzed by immunohistochemistry for protein expression, and corresponding DNA samples were analyzed for FHIT promotor hypermethlyation. Reduced or absent FHIT expression was found in 75 of 114 diffuse large B-cell lymphoma (66%), but was unrelated to clinical tumor stage or patient prognosis. FHIT promotor hypermethylation was observed in 29 of 93 (23%) interpretable diffuse large B-cell lymphoma. Hypermethylation was not significantly correlated to protein expression loss, which could be explained by competing mechanisms for FHIT inactivation in a substantial fraction of non FHIT hypermethylated diffuse large B-cell lymphoma. Hypermethylation was significantly associated with poor prognosis of diffuse large B-cell lymphoma patients and predominantly seen in nongerminal center diffuse large B-cell lymphoma (27%), but less frequent (13%) in germinal center diffuse large B-cell lymphoma. In summary, these data suggest that promotor hypermethylation is responsible for reduced FHIT expression in a substantial subset of diffuse large B-cell lymphoma, which is primarily composed of nongerminal center subtype with poor patient prognosis.     

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.     

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.     

Aflatoxin B1 effects on ovarian follicular growth and atresia in the rat

For this investigation, 28 female healthy adult Wistar rats were selected. The animals were divided into four groups (n?=?7 per group): control, test group 1, test group 2 and test group 3. Each rat in test groups 1, 2 and 3, received 0.8 ppm, 1.6 ppm and 3.2 ppm aflatoxin B1 (AFB1), respectively, via gavage for a period of 25 days. The control group received distilled water only. All tissue specimens were processed for routine paraffin embedding and serial cross-sections cut at 5–7 μm and stained with haematoxylin–eosin. Both histomorphologic and histomorphometric analysis was performed under light microscopy. An increase in the concentration of AFB1 resulted in a reduction in the population of healthy primordial, primary, secondary and tertiary follicles. The greatest reduction was in seen in group 3 (with 3.2 ppm AFB1/day). In all test groups, due to an increase in AFB1 concentration, in both the right and left ovaries, all types of atretic follicles, including primordial, primary, secondary, and tertiary atretic follicles were significantly increased (P?<?0.01). In conclusion, AFB1 is toxic for all type of ovarian follicles, including non-growing and growing follicles and exerts an atretogenic effect on all types of ovarian follicles. The atretogenic effect of AFB1 is dose dependant. Due to its toxic effects (gametotoxicity), the resting pool of ovarian follicles (primordial follicles) decreases significantly. The ovulatory follicular population either decreases or is completely depleted.