Eugenia jambolana extract reduces the systemic exposure of Sitagliptin and improves conditions associated with diabetes: A pharmacokinetic and a pharmacodynamic herb-drug interaction study.

Eugenia jambolana (EJ) is an Indian traditional herb widely used for the treatment of diabetes mellitus. This herb is globally marketed as single or multi herb formulations. Many diabetes patients consume EJ extract oral hypoglycemic drugs together. This calls for a need to assess risks versus benefit of this co-administration. In present investigation, pharmacodynamic and pharmacokinetic interactions of aqueous extract of EJ seeds at the dose of 400 mg/kg are studied with 10 mg/kg of oral hypoglycaemic drug sitagliptin (SITA) by co-administrating them for 28 days in streptozotocin (STZ) induced diabetic rats. The pharmacokinetic parameters of SITA were determined using HPLC-ESI-MS/MS and it was found that the combination treatment reduces the systemic exposure of SITA by showing 38.70% reduction in concentration maximum (Cmax) and 22.40% reduction in area under curve (AUC). Despite low levels of SITA, the combination demonstrated a significant reduction in blood glucose level when compared with individual drug and individual extract administered groups during pharmacodynamic study. In addition, the liver function, the kidney function and the lipid parameters were found to be significantly improved and beneficial effects were found with respect to food intake and water intake and urine output in case of combination treatment groups when compared with individual treatment groups. Histopathological examination of pancreatic tissue suggests its significant recovery of having normal acinus with better cell protection in combination treatment. In conclusion, the combination treatment demonstrated reduced systemic exposure of SITA without compromising on its antihyperglycemic activity and improvement in conditions associated with diabetes.

Changes in the multidisciplinary management of rectal cancer from 2009 to 2015 and associated improvements in short-term outcomes.

AIM: Significant recent changes in management of locally advanced rectal cancer (LARC) include preoperative staging, use of extended neoadjuvant therapies and minimally invasive surgery (MIS). This study was aimed at characterizing these changes and associated short-term outcomes. METHOD: We retrospectively analysed treatment and outcome data from patients with T3/4 or N+ LARC ≤ 15 cm from the anal verge who were evaluated at a comprehensive cancer centre in 2009-2015. RESULTS: In total, 798 patients were identified and grouped into five cohorts based on treatment year: 2009-2010, 2011, 2012, 2013 and 2014-2015. Temporal changes included increased reliance on MRI staging, from 57% in 2009-2010 to 98% in 2014-2015 (P < 0.001); increased use of total neoadjuvant therapy, from 17% to 76% (P < 0.001); and increased use of MIS, from 33% to 70% (P < 0.001). Concurrently, median hospital stay decreased (from 7 to 5 days; P < 0.001), as did the rates of Grade III-V complications (from 13% to 7%; P < 0.05), surgical site infections (from 24% to 8%; P < 0.001), anastomotic leak (from 11% to 3%; P < 0.05) and positive circumferential resection margin (from 9% to 4%; P < 0.05). TNM downstaging increased from 62% to 74% (P = 0.002). CONCLUSION: Shifts toward MRI-based staging, total neoadjuvant therapy and MIS occurred between 2009 and 2015. Over the same period, treatment responses improved, and lengths of stay and the incidence of complications decreased.

Isolation and characterization of Cu/Zn-superoxide dismutase in Fasciola gigantica.

A full-length complementary DNA (cDNA) encoding Cu/Zn-superoxide dismutase was isolated from Fasciola gigantica that on nucleotide sequencing showed a close homology (98.9%) with Cu/Zn-superoxide dismutase (SOD) of the temperate liver fluke, F. hepatica. Expression of the gene was found in all the three developmental stages of the parasite viz. adult, newly excysted juvenile and metacercaria at transcriptional level by reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. F. gigantica Cu/Zn-SOD cDNA was cloned and expressed in Escherichia coli. Enzyme activity of the recombinant protein was determined by nitroblue tetrazolium (NBT)-polyacrylamide gel electrophoresis (PAGE) and this activity was inactivated by hydrogen peroxide but not by sodium azide, indicating that the recombinant protein is Cu/Zn-SOD. The enzyme activity was relatively stable at a broad pH range of pH 4.0-10.0. Native Cu/Zn-superoxide dismutase protein was detected in the somatic extract and excretory-secretory products of the adult F. gigantica by Western blotting. NBT-PAGE showed a single Cu/Zn-SOD present in the somatic extract while three SODs are released ex vivo by the adult parasite. The recombinant superoxide dismutase did not react with the serum from buffaloes infected with F. gigantica. The role of this enzyme in defense by the parasite against the host reactive oxygen species is discussed.

A case of adult chronic copper self-intoxication resulting in cirrhosis.

Copper "supplements" taken in a dose of 30-60 mg/day during 3 years caused severe liver cirrhosis necessitating orthotopic liver transplantation.

Non-volatile N-nitroso compounds in human feces.

A bacterial mutagen has been detected in ether extracts of freeze-dried feces of humans on Western diet. Several types of evidence suggest that nitroso compounds are present in human feces and the mutagen could be a nitroso compound. Ascorbic acid supplement in the diet reduces the levels of both the mutagens and nitroso compounds in the feces.