The use of currently available antihyperglycemic agents can be limited by contraindications; cost; renal and hepatic dosage adjustments; dosing schedules; and adverse effects such as gastrointestinal upset, weight gain, and hypoglycemia. These limitations have led the pharmaceutical industry to identify and pursue alternative therapies. Sodium glucose cotransporter-2 (SGLT-2) inhibitors belong to a new class of diabetes drugs and have a novel mechanism of action. These agents are unique in that they increase glucose excretion, independent of insulin secretion, by inhibiting the renal reabsorption of glucose, inducing glycosuria. To summarize the current evidence for SGLT-2 inhibitor therapy, we reviewed abstracts and published data from human trials evaluating the efficacy and safety of dapagliflozin, canagliflozin, and empagliflozin through February 2013. Data from these trials suggest that SGLT-2 inhibitors are able to lower hemoglobin A1c and fasting blood glucose when used as either monotherapy or combination therapy. Cardiometabolic benefits included a reduction in systolic blood pressure, reduction in triglycerides, and weight loss of up to 3 kg. Common and serious adverse effects including infections, cancer, and pollakiuria were identified and reviewed. Although these agents have generally demonstrated efficacy, the adverse effects associated with dapagliflozin have caused a delay in its regulatory approval. Continued research in this area will determine the risk:benefit ratio of SGLT-2 inhibitor therapy.

A dvancements in the American health care system over the last 40 years have increased awareness of the effects of hypertension and appropriate antihypertensive treatment.1 Despite this increased awareness, more than 50 million Americans are estimated to still suffer from uncontrolled hypertension.

The prevalence of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) has increased in the United States over the past 40 years. These conditions, long linked with many cardiovascular complications, have recently been linked with androgen or testosterone deficiency in men. Several pathophysiologic hypotheses exist regarding this association, with the most widely reported a relationship to obesity and insulin resistance. Several randomized trials have confirmed that when testosterone replacement therapy is given to patients with T2DM, MetS, or both, metabolic parameters such as waist circumference, hemoglobin A1c , and systolic blood pressure are significantly reduced by up to 11 cm, 1.9%, and 23 mm Hg, respectively. This has not, however, resulted in improved cardiovascular outcomes, as evidenced in studies that found increased rates of cardiovascular events following testosterone replacement therapy. In this review, we summarize the relevant literature regarding the pathophysiology and management of androgen deficiency in men with T2DM, MetS, or both.

Changes in the diversity of fish populations have been monitored during a period of improving water quality in the Mersey estuary. Historically the Mersey estuary supported a wide range of locally important fisheries, particularly for salmon, mullet, sturgeon, eels and smelt (sparling). With the advent of the Industrial Revolution, increased quantities of sewage and industrial wastes discharged to the Mersey from the Manchester area dramatically reduced the water quality and led to the depletion of fish stocks in the upper estuary. By the time the Manchester Ship Canal opened in 1894 the R. Mersey and its tributaries were heavily polluted, salmon were effectively eradicated and the fisheries in the upper estuary severely limited. By 1920 the commercially important fisheries, for shrimp and flounder, had been displaced downstream to the middle part of the estuary. The dramatic increase in industrial development around the estuary itself in the 1940s caused further deteriorations such that throughout the 1950s and early 1960s anoxic conditions in the estuary were common and fish were reportedly absent from the upper estuary for much of the time. At this time major efforts were made to improve the river and its tributaries upstream of the estuary, and within a decade the quality of river water had improved markedly ( Fig. 1). This led to some improvement in estuarine water quality such that, for example, by 1976 less than 2% of samples from the upper estuary contained no detectable dissolved oxygen compared to nearly 20% of samples taken in 1963 (Fig. 2).In 1976 the North West Water Authority instituted a regular monitoring programme by collecting fish from two industrial intake screens at Stanlow and Runcorn on the Manchester Ship Canal, which has intermittent influxes of water from the estuary. Surveys in the middle and upper estuary with a 2-m beam trawl began in 1981, and electrofishing surveys of tributaries/streams around the estuary shortly afterwards. Within one year the intake screen monitoring programme recorded 19 different species of fish of which four were freshwater species, the remainder typically estuarine or marine. By 1987 the total had risen to 40 species, ten of which were freshwater (Fig. 1). The number of different species observed in any one year ranged from nine to 17. Most of the species were encountered rarely, 33 species being seen on fewer than 5% of occasions and only three species observed on more than 50% of sampling occasions when fish were taken. This pattern was confirmed by the results of the beam trawling which produced a total of 14 different species, a maximum of seven in any one year. Both the commercial intake screen and beam trawl samples were dominated by the same species, ' whitebait ' (predominately sprat, Sprattus sprattus, with lesser numbers of young herring, CIupea harengus) and sand-goby, Pomatoschistus minutus. All species caught by beam trawling had previously been recorded from the intake screens (Figs 3,4). Other species including codling, salmon and grey mullet a...

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