Elevated expression of ISG15 in tumor cells interferes with the ubiquitin/26S proteasome pathway

IFN-stimulatory gene factor 15 (ISG15) is a ubiquitin-like protein, which is conjugated to many cellular proteins. However, its role in protein degradation is unclear. Here, we show that ISG15 is highly elevated and extensively conjugated to cellular proteins in many tumors and tumor cell lines. The increased levels of ISG15 in tumor cells were found to be associated with decreased levels of polyubiquitinated proteins. Specific knockdown of ISG15 expression using ISG15-specific small interfering RNA (siRNA) was shown to increase the levels of polyubiquitinated proteins, suggesting an antagonistic role of ISG15 in regulating ubiquitin-mediated protein turnover. Moreover, siRNA-mediated down-regulation of the major E2 for ISG15 (UbcH8), which blocked the formation of ISG15 protein conjugates, also increased the levels of polyubiquitinated proteins. Together, our results suggest that the ISG15 pathway, which is deregulated during tumorigenesis, negatively regulates the ubiquitin/proteasome pathway by interfering with protein polyubiquitination/degradation.     

Evaluation of an algorithmic approach to pediatric back pain

Pediatric patients require a systematic approach to treating back pain that minimizes the number of diagnostic studies without missing specific diagnoses. This study reviews an algorithm for the evaluation of pediatric back pain and assesses critical factors in the history and physical examination that are predictive of specific diagnoses. Eighty-seven pediatric patients with thoracic and/or lumbar back pain were treated utilizing after this algorithm. If initial plain radiographs were positive, patients were considered to have a specific diagnosis. If negative, patients with constant pain, night pain, radicular pain, and/or an abnormal neurological examination obtained a follow-up magnetic resonance imaging. Patients with negative radiographs and intermittent pain were diagnosed with nonspecific back pain. Twenty-one (24%) of 87 patients had positive radiographs and were treated for their specific diagnoses. Nineteen (29%) of 66 patients with negative radiographs had constant pain, night pain, radicular pain, and/or an abnormal neurological examination. Ten of these 19 patients had a specific diagnosis determined by magnetic resonance imaging. Therefore, 31 (36%) of 87 patients had a specific diagnosis. Back pain of other 56 patients was of a nonspecific nature. No specific diagnoses were missed at latest follow-up. Specificity for determining a specific diagnosis was very high for radicular pain (100%), abnormal neurological examination (100%), and night pain (95%). Radicular pain and an abnormal neurological examination also had high positive predictive value (100%). Lumbar pain was the most sensitive (67%) and had the highest negative predictive value (75%). This algorithm seems to be an effective tool for diagnosing pediatric back pain, and this should help to reduce costs and patient/family anxiety and to avoid unnecessary radiation exposure.     

Metastatic prostate carcinoma presenting as supraclavicular lymphadenopathy - is it unusual?

Prostate carcinoma presenting initially as supraclavicular lymphadenopathy has been increasingly reported as an uncommon presentation of the disease. The diagnosis is often made on lymph node biopsy as these patients rarely undergo digital rectal examination or serum prostate-specific antigen level measurement as part of their initial investigations. A 74-year-old man presented with supraclavicular lymphadenopathy and subsequently deteriorated with severe shortness of breath associated with venous congestion of the head and neck. The diagnosis of metastatic prostate adenocarcinoma was made only after cervical lymph node biopsy. Following the diagnosis, he was confirmed as having an abnormal prostate on digital rectal examination and a raised serum prostate-specific antigen level. The authors propose that a digital rectal examination and a serum prostate specific antigen level be included in the initial investigation process of male patients with persistent supraclavicular lymphadenopathy. This would prevent delay in diagnosis, allow early intervention and decrease patient morbidity.     

Effect of graded doses of Momordica charantia seed extract on rat sperm: scanning electron microscope study

Morphological changes in sperm of albino rats observed under scanning electron microscopy illustrate the disturbance in the plasma membrane as well as in the acrosomal membrane on treatment with effect of graded doses of alcohol seed extract from Momordica charantia. Considerable changes in the shape and size of the sperm head were observed, with the middle region of the sperm head being slightly constricted dorsoventrally. Most sperm appeared morphologically abnormal in the mid-region of the tail, with formation of a balloon-like cytoplasmic droplet. The results of this study suggest that such effects may have resulted from a general disturbance in proteins and an alteration in the cauda epididymal milieu, probably due to androgen deficiency consequent to the anti-androgenic property of Momordica charantia seeds.     

Comparative evaluation of propolis and triantibiotic mixture as an intracanal medicament against Enterococcus faecalis

Introduction

The aim of this study was to evaluate and compare the antimicrobial activity of calcium hydroxide, triantibiotic mixture (TAM), and an ethanol extract of propolis as intracanal medicaments on Enterococcus faecalis-infected root canals.

Methods

One hundred twenty extracted intact human permanent incisors were decoronated, and chemomechanical preparation of the root canal was performed. After sterilization of the samples, they were inoculated with pure culture of E. faecalis and incubated. After incubation, colony-forming units were recorded before medication. Then, samples were divided randomly into five groups (n = 24). Each group was then exposed to various intracanal medicaments, namely calcium hydroxide (group 1), TAM (group 2), propolis (group 3), ethanol (group 4), and saline as the control group (group V). The antibacterial effectiveness of the different intracanal medicament was recorded by determining the percentage reduction in colony counts (%RCC) at the end of days 1, 2, and 7. The data were statistically analyzed using one-way analysis of variance and Tukey Honestly Significant Difference (HSD) post hoc test.

Results

The %RCC was highest for propolis showing 100% reduction on day 2 followed by TAM showing 82.5%, 92.2%, and 98.4% of reduction on days 1, 2, and 3, respectively. Calcium hydroxide showed a gradual increase in antibacterial activity with a maximum of 59.4% on day 7.

Conclusions

Propolis was more effective than TAM against E. faecalis at a 2-day time period, and both were equally effective at 7 days.     

Adherence to secondary prophylaxis and disease recurrence in 536 Brazilian children with rheumatic fever

Background  

More than 15 million people worldwide have rheumatic fever (RF) and rheumatic heart disease due to RF. Secondary prophylaxis is a critical cost-effective intervention for preventing morbidity and mortality related to RF. Ensuring adequate adherence to secondary prophylaxis for RF is a challenging task. This study aimed to describe the rates of recurrent episodes of RF, quantify adherence to secondary prophylaxis, and examine the effects of medication adherence to the rates of RF in a cohort of Brazilian children and adolescents with RF.