Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells

Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of γ-rays (0.01 Gy) 4 or 20 hrs prior to high dose γ-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose γ-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose γ-ray irradiation to high dose γ-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.     

Ginsenoside Rs3, a genuine dammarane-glycoside from Korean red ginseng

A genuine dammarane-glycoside, named as ginsenoside Rs₃, was isolated from the MeOH extracts of Korean red ginseng (Panax ginseng C.A. Meyer) through repeated silica gel column chromatographies and its chemical structure was determined as (20S)-protopanaxadiol 3-O-[6″-O-acetyl-β-D-glucopyranosyl (1→2)-β-D-glucopyranoside on the basis of several spectral and physical evidences including HMBC and FAB-MS.     

Synthesis and biological evaluation of 9-[2-fluoro-4-hydroxy-3-hydroxymethyl-2-butenyl]adenine and its related compounds as open-chain analogues of neplanocin A

Novel 9-[2-fluoro-4-hydroxy-3-hydroxymethyl-2-butenyl]adenine and its related compounds were designed and synthesized as open-chain analogues of neplanocin A. Alkylation of adenine or pyrimidine bases with the mesylate4 was chosen as a simple approach to the synthesis of 2-fluoro-2-butenylated nucleosides. Mesylate4 was prepared from dihydroxyacetone dimervia four steps in 58% overall yield. The synthesized compounds were evaluated their antiviral activity against HSV, HIV and Polio viruses.     

Hydrodynamic steering effects in protein association.

Protein-ligand reaction rates are often limited by the rate of diffusional encounter of the protein and ligand in solution. Reaction rates, however, can be much greater than expected, given the necessity for correct orientation before reaction. A number of forces can affect the orientation of the protein and ligand in solution, and thus increase the reaction rate. We have considered hydrodynamic forces, produced when water molecules between protein and ligand must be pushed out of the way to allow their encounter. We have used the cleft enzymes as a model system, as they could be expected to show strong hydrodynamic effects. One particular type of hydrodynamic interaction stands out: a steering torque which occurs when the enzyme and substrate move toward each other in solution. The magnitude of this steering torque is compared to the mutual torque experienced by interacting "protein-sized" dipoles in solution. A simple model is used to demonstrate that the hydrodynamic steering torque can be 2 orders of magnitude greater than the electrostatic torque.     

Assessment of the accuracy of color Doppler flow mapping by digital image analysis

An in vitro steady flow experiment was performed in order to test the accuracy of velocity measurements obtained through color Doppler flow mapping (CDFM). Using the American Society of Echocardiography (ASE) flow phantom, low (maximum velocity = 60 cm/sec), medium (maximum velocity = 300 cm/sec) and high (maximum velocity = 600 cm/sec) speed accelerating flow fields, in which multiple aliases were visible, were imaged. A fully automatic computer algorithm was used to unwrap the aliases and to convert the CDFM to digital velocity. Packet size and wall filter frequency on the ultrasound machine were varied and the measured velocity compared to the true velocity. The results show that the velocity obtained in this way from the CDFM is very accurate at the low and medium velocities, but for the high velocity the turbulence is too intense to obtain an accurate result. There was no marked difference between the data for different packet sizes or wall filter settings.     

RENAL TRANSPLANTATION – AN EARLY EXPERIENCE

Renal transplant (RT) is now a therapy of choice for end stage renal disease (ESRD). The Nephrology Unit, Asvini started functioning in Dec 90 and to date 1298 sittings of hemodialysis have been given to 45 patients. Of these, 35 were in ESRD and 11 patients underwent renal transplantation at this hospital during the period Jan 91 – Dec 93. One patient expired after 18 months of transplantation due to infection. Early experience in screening patients for RT, use of immunosuppression, management of rejection episodes and protocol are presented with special emphasis on its relevance to the Armed Forces.KEY WORDS: Transplantation, Renal Failure, Immunosuppression, Rejection     

Inhibitory effect of the root ofCoptis japonica on catecholamine biosynthesis in PC12 cells

The effect of the root ofCoptis japonica (COPT), both the dichloromethane soluble (CH₂Cl₂) and insoluble (H₂O) fractions, on catecholamine contents and tyrosine hydroxylase (TH) activity in PC12 cells was investigated. CH₂Cl₂ and H₂O fractions showed 21 and 53% inhibitions on dopamine content, respectively, at a concentration of 40 μg/ml in medium: the H₂O fraction provided a greater inhibitory effect. The TH activity was reduced by the treatment of COPT (H₂O fraction). These results suggest that COPT has an inhibitory effect on the catecholamine biosynthesis by the reduction of TH activity in PC12 cells.     

Administration route dependency of distribution of PEGylated recombinant human tumor necrosis factor binding protein (rhTNFbp-PEG20K dimer) following i.v. and s.c. injection in rats

Administration route dependency on the distribution of PEGylated recombinant human tumor necrosis factor binding protein (rhTNFbp-PEG20K dimer) was observed following a subcutaneous (sc) and an intravenous (iv) administrationin rats. rhTNFbp-PEG20K dimer is composed of two rhTNFbp molecules (molecular weight 18,278 daltons each) joined by polyethylene glycol 2000 (PEG20K). The steady state distribution volume of rhTNFbp-PEG20K was 55 ml/kg and 359 ml/kg following the i.v. and s.c. administrations, respectively. These results suggest that the distribution of rhTNFbp-PEG20K is limited within the capillary space after i.v. administration, while rhTNFbp-PEG20K can distribute into a space (35.9% of body weight) which is between extracellular space and total body water. A lymphatic absorption may play a role in the distribution of rhTNFbp-PEG20K dimer following the sc administration. The present study suggests that the administration route of large protein molecule should be determined depending upon target sites.