1141612823Effect of recombinant ovine intereferon tau (IFN) on the ovine Mx1 promoter/enhancer region

Ovine Mx1 (oMx1) is expressed in the uterus during the estrous cycle and is strongly up-regulated during early pregnancy in the uterus and peripheral blood leukocytes. Mx proteins are GTPases which are important elements in innate immunity. Our results showed that steroids are required for oMx1 protein induction by IFN in the uterus. To addresses the role of IFN in regulating oMx1 expression, a 2.1 kb fragment containing 1.7 kb of the promoter/enhancer, exon1 and partial intron A was cloned. Serial deletions were prepared along with a clone that contained the 2 promoter-ISREs (-101 & −145) but not the intronic-ISRE (+224). An ovine uterine cell line was transfected with reporter plasmids driven by the oMx1 promoter deletion constructs. The full-length promoter was induced by IFN in a dose- and time-dependent manner. Treatment with 10,000 AVU/mL IFN increased luciferase activity 5- and 10-fold at 3 and 12 hr, respectively. Promoter deletions showed the 2 proximal ISRE (−101 and −145), but not an intronic ISRE (+244), were required for maximal response. Deletion of a distal region (−920 to −715) resulted in decreased luciferase activity (~4-fold). However, subsequent deletion of the −715 to −437 region restored maximal promoter response (~10-fold). Results suggest that regions −920 to −715 and −715 to −437 have positive and negative regulatory element binding sites, respectively. The importance of the 2 proximal ISRE sites for oMx1 promoter activation is consistent with results for the human MxA promoter. An intronic ISRE is present in the human MxA gene, however, this site may not be required for oMx1 promoter activation by IFN. Identifying positive and negative regulatory regions in oMx1 promoter may help elucidate the unique regulation of Mx1 during early pregnancy.     

Chronic lymphocytic leukemia involving the coronary arteries with accompanying acute myocardial infarction

An 83-year-old man with chronic lymphocytic leukemia (CLL) for 10 years presented with dyspnea and hypotension. Blood investigations and electrocardiogram were consistent with acute myocardial infarction. The patient deteriorated quickly and died shortly thereafter. At autopsy, there was severe atherosclerosis of the coronary arteries and an inferolateral left ventricular wall myocardial infarct. Microscopy showed that CLL involved the nodes, liver, spleen, bowel, and kidneys. The coronary artery walls were infiltrated with leukemia cells invading the tunica media and the atheromatous plaque. Infiltration of the coronary arteries by CLL is not common and the possible role in coronary syndromes is discussed.     

Drainage vs. non-drainage after cholecystectomy for acute cholecystitis：a retrospective study

Many surgeons practice prophylactic drainage after cholecystectomy without reliable evidence,this study was conducted to answer the question whether to drain or not to drain after cholecystectomy for acute calculous cholecystitis.A retrospective review of all patients who had cholecystectomy for acute cholecystitis in Aseer Central Hospital,Abha,Saudi Arabia,was conducted from April 2010 to April 2012.Data were extracted from hospital case files.Preoperative data included clinical presentation,routine investigations and liver function tests.Operative data included excessive adhesions,bleeding,bile leak,and drain insertion.Complicated cases such as pericholecystic collections,mucocele and empyema were also reported.Patients who needed therapeutic drainage were excluded.Postoperative data included hospital stay,volume of drained fluid,time of drain removal,and drain site problems.The study included 103 patients allocated into two groups;group A（n = 38） for patients with operative drain insertion and group B（n = 65） for patients without drain insertion.The number of patients with preoperative diagnosis of acute non-complicated cholecystitis was significantly greater in group B（80%） than group A（36.8%）（P 〈 0.001）.Operative time was significantly longer in group A.All patients who were converted from laparoscopic to open cholecystectomy were in group A.Multivariate analysis revealed that hospital stay was significantly（P 〈 0.001） longer in patients with preoperative complications.There was no added benefit for prophylactic drain insertion after cholecystectomy for acute calculous cholecystitis in non-complicated or in complicated cases.     

Clinical and microbiological profiles of infective endocarditis in a tertiary hospital in Aseer region, Saudi Arabia

Objectives

We aimed to evaluate demographic data, underlying cardiac abnormalities, clinical profile, microbiological features, treatments and complications of infective endocarditis (IE) in a tertiary hospital in Aseer region, Saudi Arabia.

Methods

A retrospective study of all cases with the diagnosis of definite endocarditis according to modified Duke Criteria admitted to ACH between May 2002 and April 2007. Data were reviewed on demographic and clinical data, underlying cardiac disease, microbiological findings, treatments and complications of IE.

Results

The study included 44 patients (28 males and 16 females; mean age 31.1 ± 16 years; range 13–65 years). Infective endocarditis developed on a native valve in 31 (70.5%), a mechanical prosthetic valve in 10 (22.7%), mitral valve prolapse in 2 (4.5%) and ventricular septal defect in 1 (2.3%). Rheumatic heart disease in 31 cases (70.5%) was the most common preexisting valvular abnormality in native valve endocarditis. The mitral valve was the most commonly affected valve 28 (63.6%). Fever occurred in 40 (90.9%) of the cases. Electrocardiography was abnormal in 34 cases (77.3%). Trans-thoracic and/or trans-esophageal echocardiography showed a vegetation in 22 (50%). Staphylococci in 10 cases (22.7%) and Streptococci in 8 cases (18%) were the most common causative agents and cultures were negative in 20 cases (45.5%). Twenty-two patients (50%) underwent surgical treatment. Congestive heart failure occurred in 16 (36.4%) cases, atrial fibrillation in 6 (13.6%) cases, and cerebrovascular accidents in 4 (9%) cases.

Conclusion

Our data reflects the clinical and microbiological profiles of IE in a tertiary hospital in Aseer region, Saudi Arabia.     

Measurement of urinary collagen cross-links indicate response to therapy in patients with breast cancer and bone metastases.

Objective assessment of response in bone metastases from breast cancer using radiological techniques takes up to 6 months of treatment to be certain of a response, and sclerotic metastases are not evaluable. Standard serum and urinary tumour markers may not always be utilized to predict response, as they may not be elevated, and therefore may not change on treatment. The development of the urinary pyridinoline cross-link assays which measure mature bone breakdown products have been shown to be highly sensitive and specific as a measure of bone change in osteoporosis. We have measured pyridinoline (Pyr) and deoxypyridinoline (Dpyr) cross-links sequentially in 36 breast cancer patients with bone metastases, to determine if the measurement of these analytes predicts response at an earlier stage than radiological assessment. Response was assessed by UICC criteria. Seventeen women responded to hormonal therapy, whilst 19 developed progressive disease. Both Pyr and Dpyr increased sequentially in women with progressive disease with changes becoming apparent by 8 weeks (P<0.03). In responding women, cross-link levels did not change significantly. Pyr and Dpyr were more sensitive and specific than the standard serum tumour marker CA 15-3. Urinary cross-link measurements provide a novel objective method of assessing response to treatment in women with bone metastases. Initial elevated urinary cross-link markers identify patients who tend not to respond to changes in hormonal therapy.     

Microbiota profile in new-onset pediatric Crohn’s disease: data from a non-Western population

Background

The role of microbiota in Crohn’s disease (CD) is increasingly recognized. However, most of the reports are from Western populations. Considering the possible variation from other populations, the aim of this study was to describe the microbiota profile in children with CD in Saudi Arabia, a non-Western developing country population.

Results

Significantly more abundant genera in children with CD included Fusobacterium, Peptostreptococcus, Psychrobacter, and Acinetobacter; whereas the most significantly-depleted genera included Roseburia, Clostridium, Ruminococcus, Ruminoclostridium, Intestinibacter, Mitsuokella, Megasphaera, Streptococcus, Lactobacillus, Turicibacter, and Paludibacter. Alpha diversity was significantly reduced in stool (p?=?0.03) but not in mucosa (p?=?0.31). Beta diversity showed significant difference in community composition between control and CD samples (p?=?0.03).

Conclusion

In this developing country, we found a pattern of microbiota in children with CD similar to Western literature, suggesting a role of recent dietary lifestyle changes in this population on microbiota structure.