Loperamide misuse and abuse.

OBJECTIVE: The epidemic of opioid prescription deaths in recent years resulted in the recent rescheduling of hydrocodone-containing products to restrict access to them. Opioid users have recognized that loperamide can ameliorate withdrawal symptoms and also produce euphoria in very high doses. This article discusses the potential for loperamide misuse and abuse and examines trends in the increasing number of published cases of loperamide toxicity. DESIGN: PubMed was used to search MEDLINE for case reports of loperamide abuse. SETTING: United States. MAIN OUTCOME MEASURES: Numbers of cases of loperamide misuse, characteristics of patients, reported toxicities. RESULTS: From 1985 to 2016, 54 case reports of loperamide toxicity were published, with 21 cases between 1985 and 2013 and 33 cases between 2014 and 2016. In addition, 179 cases of intentional loperamide misuse were reported to the National Poison Database System between 2008 and 2016, with more than half reported after January 1, 2014. CONCLUSION: Loperamide misuse and abuse is increasing in the United States, and pharmacists are encouraged to monitor and restrict their sales.

Endotoxin, Toll-like Receptor-4, and Atherosclerotic Heart Disease.

BACKGROUND: Endotoxin is a lipopolysaccharide (LPS) constituent of the outer membrane of most gram negative bacteria. Ubiquitous in the environment, it has been implicated as a cause or contributing factor in several disparate disorders from sepsis to heatstroke and Type II diabetes mellitus. Starting at birth, the innate immune system develops cellular defense mechanisms against environmental microbes that are in part modulated through a series of receptors known as toll-like receptors. Endotoxin, often referred to as LPS, binds to toll-like receptor 4 (TLR4)/ myeloid differentiation protein 2 (MD2) complexes on various tissues including cells of the innate immune system, smooth muscle and endothelial cells of blood vessels including coronary arteries, and adipose tissue. Entry of LPS into the systemic circulation ultimately leads to intracellular transcription of several inflammatory mediators. The subsequent inflammation has been implicated in the development and progression atherosclerosis and subsequent coronary artery disease and heart failure. OBJECTIVE: The potential roles of endotoxin and TLR4 are reviewed regarding their role in the pathogenesis of atherosclerotic heart disease. CONCLUSION: Atherosclerosis is initiated by inflammation in arterial endothelial and subendothelial cells, and inflammatory processes are implicated in its progression to clinical heart disease. Endotoxin and TLR4 play a central role in the inflammatory process, and represent potential targets for therapeutic intervention. Therapy with HMG-CoA inhibitors may reduce the expression of TLR4 on monocytes. Other therapeutic interventions targeting TLR4 expression or function may prove beneficial in atherosclerotic disease prevention and treatment.

Impact of Flipped Classroom Design on Student Performance and Perceptions in a Pharmacotherapy Course.

Objective. To determine whether a flipped classroom design would improve student performance and perceptions of the learning experience compared to traditional lecture course design in a required pharmacotherapy course for second-year pharmacy students. Design. Students viewed short online videos about the foundational concepts and answered self-assessment questions prior to face-to-face sessions involving patient case discussions. Assessment. Pretest/posttest and precourse/postcourse surveys evaluated students' short-term knowledge retention and perceptions before and after the redesigned course. The final grades improved after the redesign. Mean scores on the posttest improved from the pretest. Postcourse survey showed 88% of students were satisfied with the redesign. Students reported that they appreciated the flexibility of video viewing and knowledge application during case discussions but some also struggled with time requirements of the course. Conclusion. The redesigned course improved student test performance and perceptions of the learning experience during the first year of implementation.

Are epigenetic drugs for diabetes and obesity at our door step?

Recent interest in epigenetics has focused on small molecules aimed at modifying disease-specific gene expression, including diabetes and obesity. Several major classes of epigenetic modifier include drugs already in the marketplace as well as several in various stages of study. These classes include histone deacetylase inhibitors (HDACi), histone acetyltransferase inhibitors (HATi), protein arginine methyltransferase inhibitors (PRMTis), DNA methyltransferase inhibitors (DNMTis), histone demethylating inhibitors (HDMis), and sirtuin-activating compounds (STACs). In this review, we discuss drugs with epigenetic properties that have been identified as potential therapeutic agents in the treatment of diabetes and obesity, including those currently in clinical trials.

Predatory publishing, questionable peer review, and fraudulent conferences.

Open-access is a model for publishing scholarly, peer-reviewed journals on the Internet that relies on sources of funding other than subscription fees. Some publishers and editors have exploited the author-pays model of open-access, publishing for their own profit. Submissions are encouraged through widely distributed e-mails on behalf of a growing number of journals that may accept many or all submissions and subject them to little, if any, peer review or editorial oversight. Bogus conference invitations are distributed in a similar fashion. The results of these less than ethical practices might include loss of faculty member time and money, inappropriate article inclusions in curriculum vitae, and costs to the college or funding source.

Is Community-Acquired Methicillin-Resistant Staphylococcus aureus Coverage Needed for Cellulitis?

Methicillin-resistant Staphylococcus aureus (MRSA) has become the dominant strain of Staphylococcus aureus in many communities of the United States. As a result, many clinicians are now empirically covering for this pathogen in the treatment of various skin and soft-tissue infections. Should this practice apply to cellulitis? In order to answer this question, we defined cellulitis and reviewed the pathogenesis, microbiology, and current studies of inpatient and outpatient antimicrobial therapy. The current evidence suggests empirical MRSA coverage for community-acquired cellulitis may not be necessary in non-purulent (non-suppurative) forms of this infection. Most cases are non-purulent and not amenable to culture although antibody studies indicate streptococci are the most common etiologic agents. Current studies of antimicrobial therapy tend to agree with this finding. Empirical beta-lactam therapy directed primarily at streptococci appears sufficient for non-purulent cellulitis regardless of the prevalence of MRSA in the community.

Drug-induced gynecomastia.

Drugs account for about 20% of gynecomastia cases in men. As a number of factors can alter the estrogen:androgen ratio, several pathophysiologic mechanisms are associated with drugs causing this disorder. Antiandrogens, protease inhibitors, and nucleoside reverse transcriptase inhibitors are the most common drug causes of gynecomastia, whereas first-generation antipsychotics, spironolactone, verapamil, and cimetidine are less common causes. Other drugs have been reported rarely as causes. Treatment may involve switching to an alternative agent or may require surgery or irradiation if the causative agent cannot be discontinued. We reviewed the literature on drug-induced gynecomastia and provided another perspective by reviewing data from the United States Food and Drug Administration's Adverse Event Reporting System. Epidemiologic studies are needed to provide a more accurate description of the frequency of drug-induced gynecomastia.

Single amino acid change in the fifth transmembrane segment of the TRP Ca2+ channel causes massive degeneration of photoreceptors.

The trp gene encodes subunits of a highly Ca(2+)-permeable class of light-activated channels of Drosophila photoreceptors. The recently characterized mutation in this gene, Trp(P365), is semidominant and causes massive degeneration of photoreceptors by making the TRP channel constitutively active. We show that a single amino acid change, Phe-550 to Ile, near the beginning of the fifth transmembrane domain of TRP channel subunits is necessary to induce, and sufficient to closely mimic, the original mutant phenotypes of Trp(P365). Hypotheses are presented as to why the amino acid residues at position 550 and its immediate vicinity might be important in influencing the regulation of the TRP channel and why the substitution of Phe for Ile at this position, in particular, could result in constitutive activity of the channel.