SGLT2 inhibitors: are they safe?

Sodium–glucose linked transporter type 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs with positive cardiovascular and kidney effects. The aim of this review is to present the safety issues associated with SGLT2 inhibitors. Urogenital infections are the most frequently encountered adverse events, although tend to be mild to moderate and are easily manageable with standard treatment. Although no increased acute kidney injury risk was evident in the major trials, the mechanism of action of these drugs requires caution when they are administered in patients with extracellular volume depletion or with drugs affecting renal hemodynamics. Canagliflozin raised the risk of amputations and the rate of fractures in the CANVAS trial, although more data are necessary before drawing definite conclusions. The risk of euglycemic diabetic ketoacidosis seems to be minimal when the drugs are prescribed properly. Regarding other adverse events, SGLT2 inhibitors do not increase the risk of hypoglycemia even when co-administered with insulin, but a decrease in the dose of sulphonylureas may be needed. The available data do not point to a causative role of SGLT2 inhibitors on malignancy risk, however, these drugs should be used with caution in patients with known hematuria or history of bladder cancer. SGLT2 inhibitors seem to be safe and effective in the treatment of diabetes but more studies are required to assess their long-term safety.     

Evolution of Ebola Virus Disease from Exotic Infection to Global Health Priority,Liberia, Mid-2014

Over the span of a few weeks during July and August 2014, events in West Africa changed perceptions of Ebola virus disease (EVD) from an exotic tropical disease to a priority for global health security. We describe observations during that time of a field team from the Centers for Disease Control and Prevention and personnel of the Liberian Ministry of Health and Social Welfare. We outline the early epidemiology of EVD within Liberia, including the practical limitations on surveillance and the effect on the country’s health care system, such as infections among health care workers. During this time, priorities included strengthening EVD surveillance; establishing safe settings for EVD patient care (and considering alternative isolation and care models when Ebola Treatment Units were overwhelmed); improving infection control practices; establishing an incident management system; and working with Liberian airport authorities to implement EVD screening of departing passengers.     

Assembly of microtubules onto kinetochores of isolated mitotic chromosomes of HeLa cells.

The kinetochores of isolated HeLa cell chromosomes attached to an electron microscope specimen grid, fixed in formaldehyde, and stained with alcoholic phosphotungstic acid are visible as dark, preferentially stained structures distinct from the chromatin with which they are associated. When unfixed chromosomes are immobilized by attachment to grids and incubated with chick brain tubulin, microtubules are observed to assemble onto the kinetochores. This demonstrates the competence of kinetochores in isolated chromosomes to act in vitro as microtubule assembly sites and suggests that they also possess this capacity in vivo. In addition, the results provide a possible means for isolating and characterizing kinetochores.     

Role of the endothelium in modulating neointimal formation: vasculoprotective approaches to attenuate restenosis after percutaneous coronary interventions

Restenosis at the site of an endoluminal procedure remains a significant problem in the practice of interventional cardiology. We present current data on intimal hyperplasia, which identify the major role of endothelial cells (ECs) in the development of restenosis. Considering endothelial denudation as one of the most important mechanisms contributing to restenosis, we focus more attention on methods of accelerating restoration of endothelial continuity. Prevention of restenosis may be achieved by promoting endothelial regeneration through the use of growth factors, EC seeding, vessel reconstruction with autologous EC/fibrin matrix, and the use of estrogen-loaded stents and stents designed to capture progenitor ECs.     

Palliative dilation of esophageal carcinoma

The authors' experience with palliative dilation of 46 consecutive patients evaluated for squamous cell carcinoma of the esophagus was retrospectively reviewed. Thirty-nine of 46 patients (85%) underwent dilation in order to palliate symptoms, enable endoscopy and biopsy, or prepare for placement of an esophageal prosthesis. Thirty-two of the 46 patients (70%) were treated with radiation therapy and seven (15%) underwent placement of an esophageal prosthesis. Thirty-five of the 39 patients dilated (90%) noted improvement in swallowing, allowing resumption of a soft or regular diet. Complications were noted in three of the 39 patients dilated (8%). The authors conclude that peroral dilation is a safe, effective, and probably underutilized method of palliation in patients with squamous cell esophageal carcinoma.     

The interaction of signal transduction pathways in FRTL5 thyroid follicular cells: studies with stable expression of beta 2-adrenergic receptors.

Multiple signal transduction pathways interact in FRTL5 cells to promote thyroid follicular cell differentiated function and cell proliferation. In these cells, TSH is a tissue-specific mitogen that promotes DNA synthesis primarily through activation of adenylate cyclase. To further test the role of adenylate cyclase in regulating cell growth and differentiated function we have introduced into FRTL5 the human beta 2-adrenergic receptor (BAR) complementary DNA and have studied the ability of isoproterenol, alone and in combination with insulin-like growth factor I (IGF-I), to stimulate cAMP accumulation, iodide transport, [3H]thymidine incorporation into DNA, and cell growth. Wild-type FRTL5 were infected with a PLJ retroviral construct containing the BAR in either a sense (FRTL BAR) or antisense (FRTL RBAR) orientation, and cell populations were selected on the basis of resistance to the antibiotic geneticin. FRTL BAR expressed approximately 1.3 x 10(5) high affinity binding sites per cell for the beta 2-specific ligand, CGP-12177, while neither FRTL5 wild-type nor RBAR cells demonstrated any specific binding. FRTL BAR had significantly higher levels of intracellular cAMP, [3H]thymidine incorporation, and iodide uptake in the absence of added isoproterenol than FRTL RBAR or wild-type cells. In FRTL BAR, but not RBAR cells, isoproterenol stimulated a dose-dependent accumulation of cAMP, iodide uptake, [3H]thymidine incorporation, and cell growth. FRTL BAR and RBAR cells were equally responsive to TSH and to IGF-I. Isoproterenol enhanced the ability of IGF-I to stimulate [3H]thymidine incorporation in BAR but not RBAR cells. Isoproterenol partially inhibited the ability of TSH to stimulate cAMP generation and DNA synthesis. These studies demonstrate that activation of adenylate cyclase through the BAR introduced into FRTL5 cells by retroviral infection reproduces the range of biological effects in these cells stimulated by TSH and suggest that activation of adenylate cyclase is sufficient to stimulate thyroid differentiated function and cell growth. FRTL BAR cells will provide an interesting model system with which to study the heterologous regulation of both TSH and BARs through activation of a common signal transduction pathway, adenylate cyclase.     

Controlling HIV in Africa: effectiveness and cost of an intervention in a high-frequency STD transmitter core group

Since 1985, a population of over 1,000 predominantly HIV-positive female prostitutes residing in a low-income area of Nairobi, has been enrolled in a sexually transmitted disease (STD)/HIV control programme. The major elements of the programme include the diagnosis and treatment of conventional STD, and the promotion of condom use to prevent the transmission of HIV and other sexually transmitted infections. Using estimates of numbers of HIV-seropositive prostitutes, numbers of sexual contacts, susceptibility of clients to HIV, HIV transmission efficiency, rates of condom use and the basic reproductive rate of HIV infection in Kenya, we estimate that the programme is responsible for preventing between 6,000 and 10,000 new cases of HIV infection per year among clients and contacts of clients. The total annual operating cost of the programme is approximately US$77,000 or between US$8.00 and US$12.00 for each case of HIV infection prevented. Programmes to reduce the transmission of HIV and other sexually transmitted infections which are targeted at high-frequency STD transmitters, such as prostitutes, can be effective and relatively inexpensive to undertake. More such programmes should be developed and evaluated in different settings.