Septic shock caused by Sphingomonas paucimobilis bacteremia in a patient with hematopoietic stem cell transplantation

Abstract: Sphingomonas paucimobilis is an aerobic gram-negative bacillus that causes a variety of infections in healthy as well as in immunocompromised individuals. The organism is usually susceptible to tetracycline, chloramphenicol, aminoglycosides, trimethoprim–sulfamethoxazole, and carbapenems. However, resistance to penicillins and the first-generation cephalosporins is commonly encountered. Reported here is a patient with acute myeloid leukemia who developed S. paucimobilis bacteremia complicated by septic shock just before receiving an autologous hematopoietic stem cell transplant (SCT) at King Faisal Specialist Hospital and Research Centre in Riyadh. The septic episode was successfully treated in the intensive care unit. To our knowledge, this is the first case report of septic shock caused by S . paucimobilis bacteremia in a hematopoietic SCT recipient.     

Cerebrotendinous xanthomatosis in a Saudi Arabian family-genotyping and long-term follow-up

A Saudi Arabian family is described in which there were 2 siblings with typical features of cerebral xanthomatosis CTX including premature cataracts, xanthomata of the Achilles tendons, neuro-psychiatric disturbances, and atherosclerosis. The 2 patients were homozygous for a point mutation in the mitochondrial 27-hydroxylase gene CYP27A1, OMIM 606530 located in the splice site of intron 6, where G was exchanged for A IVS6+1G>A. Their parents were cousins, 5 siblings were healthy, 2 were heterozygous for the mutation, and one showed the wild-type genotype. The father was heterozygous for the mutation, while the other family members were not tested. The progress of the 2 CTX patients over 14 years is described; firstly when they were receiving treatment with chenodeoxycholic acid; when this medication was not available, and later when it was restored. A hereditary hyperlipidemia was also present in this family. It is suggested that when this occurs with CTX, a more serious illness results that merits more aggressive dual therapy.     

Camel Urine Promotes Sensitization to Doxorubicin by Inhibiting Epithelial-Mesenchymal Transition and Modulating NF-κB-Snail Signaling Pathway in Breast Cancer Cells

Background: Camel urine (CU) has been used as traditional treatment in the Arabian Peninsula for centuries. Although, researchers have reported CU anti-cancer effects, the exact mechanism(s) of action involved has not been fully elucidated. The epithelial–mesenchymal transition EMT is a phenotypic switch that promotes the acquisition of a fibroblastoid-like morphology by epithelial tumor cells, resulting in enhanced tumor cell motility and invasiveness. EMT has been shown to contribute to metastasis and chemoresistance of carcinomas. For that, in the present study, we have assessed the potential mechanism (s) by which CU exert its anti-cancer effects and its possible synergistic therapeutic effect with Doxorubicin (DOX) in breast cancer cells. Methods: Determination of anti-proliferative and apoptosis validation of CU was performed by 3-(4,5-Dimethylthiazol-2-yl)-2,5,-diphenyltetrazolium bromide (MTT), annexin-V-fluorescein isothiocyanate assays, and Western blot. EMT protein markers, migration and invasion of cells were determined by Western blot or immunofluorescent staining, Scratch assay, Transwell invasion assay, respectively. Results: CU applied a significant anti-cancer effect on breast cancer cells via induction of DNA damage and apoptosis in a concentration- and time-dependent manner. Also, CU remarkably reversed the EMT by downregulating N-cadherin and Vimentin expression and upregulating E-cadherin expression. As a result, the stemness, migration and invasion of breast cancer cells were also inhibited, which was likely mediated by NF-κB-Snail signalling pathway and its downstream inflammatory effectors. CU successfully enhanced DOX cytotoxicity by reversing EMT which possibly through inhibition of NF-κB-Snail signalling and subsequently inflammation.  Thus, our study provides new mechanistic bases for the therapeutic application of CU that may improve the outcomes of anti-cancer chemotherapy.     

Over-expression of mitogen-activated protein kinase phosphatase-2 enhances adhesion molecule expression and protects against apoptosis in human endothelial cells

BACKGROUND AND PURPOSE

We assessed the effects of over-expressing the dual-specific phosphatase, mitogen-activated protein (MAP) kinase phosphatase-2 (MKP-2), in human umbilical vein endothelial cells (HUVECs) on inflammatory protein expression and apoptosis, two key features of endothelial dysfunction in disease.

EXPERIMENTAL APPROACHES

We infected HUVECs for 40 h with an adenoviral version of MKP-2 (Adv.MKP-2). Tumour necrosis factor (TNF)-α-stimulated phosphorylation of MAP kinase and protein expression was measured by Western blotting. Cellular apoptosis was assayed by FACS.

KEY RESULTS

Infection with Adv.MKP-2 selectively abolished TNF-α-mediated c-Jun-N-terminal kinase (JNK) activation and had little effect upon extracellular signal-regulated kinase or p38 MAP kinase. Adv.MKP-2 abolished COX-2 expression, while induction of the endothelial cell adhesion molecules, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM), two NFκB-dependent proteins, was not affected. However, when ICAM and VCAM expression was partly reduced by blockade of the NFκB pathway, Adv.MKP-2 was able to reverse this inhibition. This correlated with enhanced TNF-α-induced loss of the inhibitor of κB (IκB)α loss, a marker of NFκB activation. TNF-α in combination with NFκB blockade also increased HUVEC apoptosis; this was significantly reversed by Adv.MKP-2. Protein markers of cellular damage and apoptosis, H2AX phosphorylation and caspase-3 cleavage, were also reversed by MKP-2 over-expression.

CONCLUSIONS AND IMPLICATIONS

Over-expression of MKP-2 had different effects upon the expression of inflammatory proteins due to a reciprocal effect upon JNK and NFκB signalling, and also prevented TNF-α-mediated endothelial cell death. These properties may make Adv.MKP-2 a potentially useful future therapy in cardiovascular diseases where endothelial dysfunction is a feature.     

The Queuine Micronutrient: Charting a Course from Microbe to Man

Micronutrients from the diet and gut microbiota are essential to human health and wellbeing. Arguably, among the most intriguing and enigmatic of these micronutrients is queuine, an elaborate 7-deazaguanine derivative made exclusively by eubacteria and salvaged by animal, plant and fungal species. In eubacteria and eukaryotes, queuine is found as the sugar nucleotide queuosine within the anticodon loop of transfer RNA isoacceptors for the amino acids tyrosine, asparagine, aspartic acid and histidine. The physiological requirement for the ancient queuine molecule and queuosine modified transfer RNA has been the subject of varied scientific interrogations for over four decades, establishing relationships to development, proliferation, metabolism, cancer, and tyrosine biosynthesis in eukaryotes and to invasion and proliferation in pathogenic bacteria, in addition to ribosomal frameshifting in viruses. These varied effects may be rationalized by an important, if ill-defined, contribution to protein translation or may manifest from other presently unidentified mechanisms. This article will examine the current understanding of queuine uptake, tRNA incorporation and salvage by eukaryotic organisms and consider some of the physiological consequence arising from deficiency in this elusive and lesser-recognized micronutrient.     

Conscious sedation for awake craniotomy in intra-operative magnetic resonance imaging operating theatre (IMRI OT) environment

This technical report disrobes the first case in Intra-operative Magnatic Resonance Imaging operating theatre (iMRI OT) (BrainSuite), of Awake Craniotomy. The procedure was for frontal lobe glioma excision in 24 y. old man. He was scheduled to undergo eloquent cortex language mapping intra-operatively. He was motivated and was excited to see the operating theatre. He requested to take his photos while operated upon. The authors adapted conscious sedation technique with variable depth according to Ramsey's scale, in order to revert to awake state to perform the intended neurosurgical procedure. Patient tolerated the situation satisfactory and was cooperative till the finish without any event. We elicit in this report the special environment of iMRI OT for lengthy operation in pinned fixed patient having craniotomy. The text shows the special environment, its demands and its possible difficulties.