β‐Lactam antibiotics are among the most important drugs used to fight bacterial infection. Overuse and misuse of β‐lactam antibiotics has caused the evolution of resistance mechanisms, allowing pathogenic bacteria to survive antibiotic treatment. The major source of resistance to β‐lactam antibiotics occurs through production of enzymes called β‐lactamases capable of catalyzing hydrolysis of the β‐lactam rings in these drug compounds. The metallo‐β‐lactamases have become a major threat due to their broad substrate specificities; there are no clinically useful inhibitors for these metalloenzymes. We have obtained single‐stranded DNA’s that are potent inhibitors of the Bacillus cereus 5/B/6 metallo‐β‐lactamase. These are rapid, reversible, non‐competitive inhibitors of the metalloenzyme, with Ki and Ki′ values in the nanomolar range. The inhibition patterns and metal ion dependence of their inhibition suggest that the oligonucleotides alter the coordination of the active site metal ion(s); inhibition is efficient and highly specific. Microbiological growth experiments, using combinations of ssDNA with the β‐lactam antibiotic cephalexin, reveal that the inhibitor is capable of causing cell death in liquid cultures of both Gram‐positive and Gram‐negative metallo‐β‐lactamase producing bacteria in the micromolar concentration range.
Background Among the restrictive procedures the role of restrictive vs. resecting the stomach is still ambiguous. This study evaluate which is the role of the stomach with respect to blood glucose levels (BG) and percent excess weight loss (EWL) over the 18 months after restrictive procedures in morbid obese diabetic patients. Methods We retrospectively compared a group of patients who underwent partial gastrectomy (just part of the gastric body) with gastric banding (GBSR; n = 27), sleeve gastrectomy (part of gastric body and complete fundus resection; LSG; n = 53) to laparoscopic gastric banding (LAGB; n = 100). Differences among groups at 3, 6, 12, and 18 months were evaluated by analysis of variance. The three cohorts were diabetic patients similar in BMI, age, and gender. Results At 12 and 18 months, LSG had higher EWL ( P < 0.05) and lower BG ( P < 0.05) than did either LAGB or GBSR. There were no operative deaths. Complications: LAGB—two staple-line oozing, two wound infections; LSG—one hemorrhage, two staple-line oozing, two leaks; GBSR—one hemorrhage, two wound infections. All complications were readily treated. Conclusions LSG provides better weight loss and glucose control at 1 year and 1.5 years after surgery than does either LAGB or GBSR, suggesting that gastric fundus resection plays an important, not yet well-defined, role.
Fat is either white or brown, the latter being found principally in neonates. White fat, which comprises adipocytes, pre-adipocytes, macrophages, endothelial cells, fibroblasts, and leukocytes, actively participates in hormonal and inflammatory systems. Adipokines include hormones such as leptin, adiponectin, visfatin, apelin, vaspin, hepcidine, chemerin, omentin, and inflammatory cytokines, including tumor necrosis factor alpha (TNF), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator protein (PAI). Multiple roles in metabolic and inflammatory responses have been assigned to adipokines; this review describes the molecular actions and clinical significance of the more important adipokines. The array of adipokines evidences diverse roles for adipose tissue, which looms large in the mediators of inflammation and metabolism. For this reason, treating obesity is more than a reduction of excess fat; it is also the treatment of obesity's comorbidities, many of which will some day be treated by drugs that counteract derangements induced by adipokine excesses.