Interleukin, tumor necrosis factor-α and C-reactive protein profiles in melancholic and non-melancholic depression: A systematic review.

OBJECTIVE: The current diagnostic criteria for major depressive disorder (MDD) do not allow prediction of prognosis and therapeutic response. A possible strategy to improve this situation is the identification of depression subtypes on the bases of biomarkers reflecting underlying pathological processes such as neuro-inflammation. METHODS: The PubMed/Medline database was searched until Apr 25th, 2017. In the initial search 1018 articles were retrieved, which were subsequently screened and only selected when the inclusion and exclusion criteria were fulfilled. RESULTS: Eight eligible studies were found. Overall, serum interleukin-6 and 1ß values were increased in the melancholic MDD subtype compared to controls and the non-melancholic MDD subtype. C-reactive protein was increased in non-melancholic MDD in 2 out of 4 studies, while there was no difference for tumor necrosis factor-α and interleukin-2 and 10. CONCLUSION: Given the paucity of eligible studies the tentative conclusion must be drawn that peripheral inflammation markers have limited added value thus far to distinguish between melancholic and non-melancholic depression. To allow for a more definitive conclusion, further research is warranted using a broader panel of inflammatory markers in MDD subtypes, preferably based on a general consensus regarding diagnostic criteria and subtype definitions.

Reductive metabolism of the dinitrobenzamide mustard anticancer prodrug PR-104 in mice.

PURPOSE: PR-104, a bioreductive prodrug in clinical trial, is a phosphate ester which is rapidly metabolized to the corresponding alcohol PR-104A. This dinitrobenzamide mustard is activated by reduction to hydroxylamine (PR-104H) and amine (PR-104M) metabolites selectively in hypoxic cells, and also independently of hypoxia by aldo-keto reductase (AKR) 1C3 in some tumors. Here, we evaluate reductive metabolism of PR-104A in mice and its significance for host toxicity. METHODS: The pharmacokinetics of PR-104, PR-104A and its reduced metabolites were investigated in plasma and tissues of mice (with and without SiHa or H460 tumor xenografts) and effects of potential oxidoreductase inhibitors were evaluated. RESULTS: Pharmacokinetic studies identified extensive non-tumor reduction of PR-104A to the 5-amine PR-104H (identity of which was confirmed by chemical synthesis), especially in liver. However, high concentrations of PR-104H in tumors that suggested intra-tumor activation is also significant. The tissue distribution of PR-104M/H was broadly consistent with the target organ toxicities of PR-104 (bone marrow, intestines and liver). Surprisingly, hepatic nitroreduction was not enhanced when the liver was made more hypoxic by hepatic artery ligation or breathing of 10% oxygen. A screen of non-steroidal anti-inflammatory drugs identified naproxen as an effective AKR1C3 inhibitor in human tumor cell cultures and xenografts, suggesting its potential use to ameliorate PR-104 toxicity in patients. However, neither naproxen nor the pan-CYP inhibitor 1-aminobenzotriazole inhibited normal tissue reduction of PR-104A in mice. CONCLUSIONS: PR-104 is extensively reduced in mouse tissues, apparently via oxygen-independent two-electron reduction, with a tissue distribution that broadly reflects toxicity.

Is there a benefit to preoperative weight loss in gastric bypass patients? A prospective randomized trial.

BACKGROUND: Roux-en-Y gastric bypass surgery is the leading surgical treatment of morbid obesity in the United States. The role of preoperative weight loss in gastric bypass surgery remains controversial. We performed a prospective randomized trial to determine whether preoperative weight loss results in better outcomes after laparoscopic gastric bypass. METHODS: A total of 100 patients undergoing laparoscopic gastric bypass surgery from May 2004 to October 2005 were randomized preoperatively to either a weight loss group with a 10% weight loss requirement or a group that had no weight loss requirements. The patients were followed prospectively. The variables analyzed included perioperative complications, operative time, postoperative weight loss, and resolution of co-morbidities. RESULTS: Data were available for 26 patients in the weight loss group and 35 in the nonweight loss group. The 2 groups had similar preoperative characteristics, conversion and complication rates, and resolution of co-morbidities. The initial body mass index was 48.7 kg/m(2) and 49.3 kg/m(2) for the weight loss group and nonweight loss group, respectively (P = NS). The preoperative body mass index was 44.5 kg/m(2) and 50.7 kg/m(2) for the weight loss group and nonweight loss group, respectively (P = 0.0027). The operative time was 220.2 and 257.6 minutes for the 2 groups (P = 0.0084). The percentage of excess weight loss at 3 and 6 months for the weight loss group and nonweight loss group was 44.1% and 33.1% (P = 0.0267) and 53.9% and 50.9% (P = NS), respectively. The interval to surgery from the initial consultation was 5.4 months and 5.2 months for the 2 groups (P = NS). CONCLUSIONS: Preoperative weight loss before laparoscopic Roux-en-Y gastric bypass was associated with a decrease in the operating room time and an improved percentage of excess weight loss in the short term. Preoperative weight loss, however, did not affect the major complication or conversion rates, and its long-term effects were not apparent through this study. Also, preoperative weight loss did not have any bearing on the resolution of co-morbidities.