Low Anterior Resection Syndrome.

PURPOSE OF REVIEW: Low anterior resection syndrome is a highly prevalent condition that can develop after anal sphincter-sparing surgery for rectal cancer and impair quality of life. In this review, we summarize the major features and pathophysiology of this syndrome and discuss treatment approaches. RECENT FINDINGS: Quality of life correlates significantly with severity of low anterior resection syndrome. Prompt assessment and initiation of therapy are essential to rehabilitating damaged mechanical and neural structures. Anorectal manometry demonstrates a global decrease in sphincteric function postoperatively, though in many patients, function does recover. Transanal irrigation, pelvic floor rehabilitation, and biofeedback are the mainstays of the treatment of major LARS. Definitive stoma can be considered in therapy refractory LARS > 2 years. The development of low anterior resection syndrome likely involves an interplay between mechanical and neural pathways. Clinically, patients present at varying levels of severity, and scoring systems are available to help assess patient symptoms and guide therapy. Treatment approaches range from conservative therapies to biofeedback and sacral nerve stimulation. Future randomized controlled trials aimed at risk stratification of patients and development of severity-based treatment algorithms are warranted.

Detoxification of chlorella supplement on heterocyclic amines in Korean young adults.

Heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) have been established as carcinogenic chemicals in Western diet. This study was performed to estimate HCA exposure levels in Korean daily life and to assess the ability of Chlorella vulgaris to detoxify carcinogenic HCAs in a randomized, double blind, placebo-controlled crossover study with chlorella supplement (N=6, all females, age: 27.17±7.73yr) for 2 weeks. We analyzed HCAs in hydrolyzed urine specimens using LC/TOF-MS. As results, urinary levels of MeIQx, PhIP, and IQx-8-COOH were 323.36±220.11ng/L, 351.59±254.93ng/L, and 130.85±83.22ng/L, respectively. Effects of chlorella to reduce urinary MeIQx were marginally significant (before, 430±226.86pg/mL vs. after, 174.45±101.65pg/mL: 0.05

Critical review of preclinical approaches to investigate cytochrome p450-mediated therapeutic protein drug-drug interactions and recommendations for best practices: a white paper.

Drug-drug interactions (DDIs) between therapeutic proteins (TPs) and small-molecule drugs have recently drawn the attention of regulatory agencies, the pharmaceutical industry, and academia. TP-DDIs are mainly caused by proinflammatory cytokine or cytokine modulator-mediated effects on the expression of cytochrome P450 enzymes. To build consensus among industry and regulatory agencies on expectations and challenges in this area, a working group was initiated to review the preclinical state of the art. This white paper represents the observations and recommendations of the working group on the value of in vitro human hepatocyte studies for the prediction of clinical TP-DDI. The white paper was developed following a "Workshop on Recent Advances in the Investigation of Therapeutic Protein Drug-Drug Interactions: Preclinical and Clinical Approaches" held at the Food and Drug Administration White Oak Conference Center on June 4 and 5, 2012. Results of a workshop poll, cross-laboratory data comparisons, and the overall recommendations of the in vitro working group are presented herein. The working group observed that evaluation of TP-DDI for anticytokine monoclonal antibodies is currently best accomplished with a clinical study in patients with inflammatory disease. Treatment-induced changes in appropriate biomarkers in phase 2 and 3 studies may indicate the potential for a clinically measurable treatment effect on cytochrome P450 enzymes. Cytokine-mediated DDIs observed with anti-inflammatory TPs cannot currently be predicted using in vitro data. Future success in predicting clinical TP-DDIs will require an understanding of disease biology, physiologically relevant in vitro systems, and more examples of well conducted clinical TP-DDI trials.

Folate status of gut microbiome affects Caenorhabditis elegans lifespan.

In a paper in BMC Biology Virk et al. show that Caenorhabditis elegans lifespan is extended in response to a diet of folate-deficient Escherichia coli. The deficiencies in folate biosynthesis were due to an aroD mutation, or treatment of E. coli with sulfa drugs, which are mimics of the folate precursor para-aminobenzoic acid. This study suggests that pharmacological manipulation of the gut microbiome folate status may be a viable approach to slow animal aging, and raises questions about folate supplementation.

Bilateral pneumothoraces secondary to acupuncture therapy.

Acupuncture is becoming increasingly popular in the United States for a wide variety of uses, ranging from the treatment of chronic back pain to aiding in addiction therapy. As this form of complementary and alternative medicine becomes more prevalent in certain areas of the country, it is of paramount importance that the emergency physician be familiar with its methods and potential complications. In general, acupuncture is perceived as fairly safe. However, it is not without risks or side effects. In this case report, we discuss the history, methods, and common complications of acupuncture in the context of a patient who presented to the Emergency Department (ED) with bilateral pneumothoraces secondary to acupuncture therapy.

Inhibition of Abeta42 aggregation using peptides selected from combinatorial libraries.

Increasing evidence suggests that the aggregation of the small peptide Abeta42 plays an important role in the development of Alzheimer's disease. Inhibiting the initial aggregation of Abeta42 may be an effective treatment for preventing, or slowing, the onset of the disease. Using an in vivo screen based on the enzyme EGFP, we have searched through two combinatorially diverse peptide libraries to identify peptides capable of inhibiting Abeta42 aggregation. From this initial screen, three candidate peptides were selected and characterized. ThT studies indicated that the selected peptides were capable of inhibiting amyloid aggregation. Additional ThT studies showed that one of the selected peptides was capable of disaggregating preformed Abeta42 fibers.