Room scatter studies in the air kerma strength standardization of the Amersham CDCS-J-type 137Cs source: a Monte Carlo study

Corrections for room scatter, [kSC (d, H)]RM, as a function of source-to-detector distance, d, and source-to-floor-height, H, and also departure from constant room scatter. ks1, have been computed for rooms of various sizes using Monte Carlo methods for air kerma strength standardization of the Amersham CDCS-J-type 137Cs brachytherapy source. These corrections will also be applicable to any type of 137Cs source that may be considered for standardization. It was found that, depending upon the relative position of the source with respect to the surrounding concrete scattering surfaces (side walls, floor and ceiling) and different set of d values, the assumption of constant room scatter overestimated the air kerma strength, Sk, by between 0.2% and 0.6%.     

Effects of carbenoxolone on syncytial electrical properties and junction potentials of guinea-pig vas deferens

The effects of the putative gap junction blocker carbenoxolone on smooth muscle syncytial properties and junction potentials were studied in guinea pig vas deferens (GPVD). Treatment with 50 μM carbenoxolone reversibly and significantly increased input resistance (R _in) (by 682.5 ± 326.0 %, P < 0.05) and abolished cable potentials within 6–7 mins of incubation, without disturbing resting membrane potential. Carbenoxolone reversibly and significantly increased the amplitude of spontaneous excitatory junction potentials (sEJPs) by 96.9 ± 35.45% (P < 0.05), shifted their amplitude distribution rightwards, and reduced their frequency of occurrence by 58.17 ± 17.7% (P < 0.05), without altering their time courses. Similarly, carbenoxolone increased the amplitude of evoked excitatory junction potentials (eEJPs) by 17.7 ± 5.88% and τ _decay by 19.43 ± 8.29% (P < 0.05). Our results indicate that carbenoxolone alters the electrical properties and junctional potentials of the GPVD by a mechanism consistent with a relatively specific block of gap junctions. These results suggest that gap junction mediated cell-to-cell communication may significantly modulate the electrical properties and junctional potentials of the GPVD and consequently the physiological functioning of this tissue.     

Biaryl ureas as potent and orally efficacious melanin concentrating hormone receptor 1 antagonists for the treatment of obesity

Herein, we report a small molecule MCH-R1 antagonist which demonstrates oral efficacy in chronic rodent models. Substituted phenyl biaryl urea derivatives were synthesized and evaluated as MCH-R1 antagonists for the treatment of obesity. The structure-activity relationship studies in this series resulted in identification of urea 1 as a potent and selective MCH-R1 antagonist. Compound 1 exhibited oral efficacy in chronic (28 d) rodent models at 3-30 mpk showing significant reduction in food intake and weight gain relative to controls.     

Discovery of 4-[(Z)-(4-bromophenyl)- (ethoxyimino)methyl]-1'-[(2,4-dimethyl-3- pyridinyl)carbonyl]-4'-methyl-1,4'- bipiperidine N-oxide (SCH 351125): an orally bioavailable human CCR5 antagonist for the treatment of HIV infection

Structure-activity studies on piperidino-piperidine 3 led to the discovery of SCH 351125 (1), a selective CCR5 antagonist with potent activity against RANTES binding (K(i) = 2 nM), which possesses subnanomolar activity in blocking viral entry and has excellent antiviral potency versus a panel of primary HIV-1 viral isolates. Compound 1, which has good oral bioavailability in rats, dogs, and monkeys, is proposed as a potential therapeutic agent for the treatment of HIV-1 and has entered human clinical trials.     

Serum amylase on the night of surgery predicts clinically significant pancreatic fistula after pancreaticoduodenectomy

Objectives

Drainage after pancreaticoduodenectomy (PD) remains controversial because the risk for uncontrolled postoperative pancreatic fistula (POPF) must be balanced against the potential morbidity associated with prolonged and possibly unnecessary drainage. This study investigated the utility of the level of serum amylase on the night of surgery [postoperative day (PoD) 0 serum amylase] to predict POPF.

Methods

A total of 185 patients who underwent PD were studied. Occurrences of POPF were graded using the International Study Group on Pancreatic Fistula (ISGPF) classification. Receiver operating characteristic (ROC) analysis identified a threshold value of PoD 0 serum amylase associated with clinically significant POPF (ISGPF Grades B and C) in a test cohort (n = 45). The accuracy of this threshold value was then tested in a validation cohort (n = 140).

Results

Overall, 43 (23.2%) patients developed clinically significant POPF. The threshold value of PoD 0 serum amylase for the identification of clinically significant POPF was ≥130 IU/l (P = 0.003). Serum amylase of <130 IU/l had a negative predictive value of 88.8% for clinically significant POPF (P < 0.001). Serum amylase of ≥130 IU/l on PoD 0 and a soft pancreatic parenchyma were independent risk factors for clinically significant POPF.

Conclusions

Postoperative day 0 serum amylase of <130 IU/l allows for the early and accurate categorization of patients at least risk for clinically significant POPF and may identify patients suitable for early drain removal.     

Hemangiomas revisited: the useful,the unusual and the new Part 2: endangering hemangiomas and treatment

Hemangiomas, although benign tumors, can when located in particular regions threaten vital structures or in certain clinical circumstances be associated with other abnormalities, carrying significant morbidity and mortality. We review these endangering hemangiomas. We also discuss briefly the treatment with emphasis on the recent use of propranolol.     

Effects of the inhibition of cytosolic phospholipase A<Subscript>2</Subscript>α in non-small cell lung cancer cells

Purpose  

The aim of this study was to investigate the expression of cPLA₂α in non-small lung cancer cell lines and tissues, and we sought to determine the in vitro effects of the pyrrolidine-2 inhibitor on cPLA₂α sensitivity in three different non-small lung cancer cell lines.