In vitro investigation of the apoptotic effect of heparin on lymphoblasts by using flow cytometric DNA analysis and fluorometric caspase-3 and -8 activities

The apoptotic effect of heparin on the lymphoblasts obtained from 12 newly diagnosed children with acute lymphoblastic leukemia (ALL) was investigated in vitro. The lymphoblasts were incubated with 0, 10, and 20 U/mL heparin concentrations at 0, 1, and 2 h. The percentages of the apoptotic lymphoblasts were calculated by flow cytometry (FCM), and activities of caspase-3 and -8 were simultaneously measured by fluorometric protease activity method. The apoptotic effect of heparin on the lymphoblasts was determined in 10 and 20 U/mL heparin concentrations (p < 0.005 and p < 0.001, respectively) while no apoptosis was detected in 0 U/mL heparin concentration at 0, 1, and 2 h. The apoptotic percentages of the lymphoblasts were higher at the first hour than those at 0 and 2 h in 10 and 20 U/mL heparin levels (p < 0.001). The highest apoptosis was found at first hour in 20 U/mL heparin concentration. Increased concentrations of heparin had an increasing effect on the percentages of the apoptotic lymphoblasts. Significantly higher caspase-3 and -8 activities were determined in 10 and 20 U/mL heparin concentrations than those in 0 U/mL heparin concentration at 0, 1, and 2 h (p < 0.001). There were no significant differences between the caspase-3 and -8 activities in 10 and 20 U/mL heparin concentrations at 1 and 2 h (p > 0.05), while statistically significant differences were simultaneously detected in the apoptotic rates of the lymphoblasts (p < 0.001). This may be due to that the study included the limited patients, or measurement of the caspase activities is a more sensitive method than the FCM analysis for determination of apoptosis because the activation time of the caspases takes a long time period. It was concluded that the apoptotic effect of heparin in vitro on lymphoblasts developed due to the extrinsic pathway of apoptosis via the caspase-3 and -8 activations in newly diagnosed ALL patients.     

Synthesis and biological evaluation of 6,7-disubstituted 4-aminopyrido[2,3-d]pyrimidines as adenosine kinase inhibitors

The synthesis and structure-activity relationship of a series of 6,7-disubstituted 4-aminopyrido[2,3-d]pyrimidines as novel non-nucleoside adenosine kinase inhibitors is described. A variety of substituents, primarily aryl, at the C6 and C7 positions of the pyridopyrimidine core were found to yield analogues that are potent inhibitors of adenosine kinase. In contrast to the 5,7-disubstituted and 5,6,7-trisubstituted pyridopyrimidine series, these analogues exhibited only modest potency to inhibit AK in intact cells.     

Binding of lead ion to bovine serum albumin studied by ion selective electrode

The binding of Pb2+ to bovine serum albumin (BSA) at neutral pH was studied using lead ion selective electrode. The binding data was treated according to Scatchard Equation. The number of binding classes and the number of binding sites, intrinsic dissociation constants and stepwise binding constants for each class were determined. Two binding classes were found. Four binding sites in the first class and five binding sites in the second class were determined. Binding in the first class was stronger than in the second. Similar binding studies were carried out with heat treated BSA. It was found that not only the number of binding sites but also the strength of binding increases upon heat treatment.     

Bone mass toxicity associated with inhalation exposure to toluene

The inhalation of a wide range of organic solvents has become popular among young adults. Toluene is one of the most commonly used solvents in industry; it is easily available and conventient to use. Many toxicologic effects on biological systems secondary to deliberate inhalation of toluene have been reported, but investigations on adverse effects associated with bone morbidity is limited. The purpose of this study is to determine bone mineralization and investigate the adverse effects of toluene on bone. The bone mineral density and content of the femoral neck of mice exposed to toluene at 300 ppm for 8 wk were measured by dual X-ray absorptiometry and found significantly reduced compared to the control group. Chronic exposure to toluene was found to affect bone metabolism, and toluene-induced changes could contribute to bone resorption and inhibition of bone formation. Toluene seems to be the responsible component for the demineralizating effects of commonly abused substances, and medical doctors must promote their education about the health hazards in those who abuse solvents especially in areas where inhalant abuse is endemic.     

Haematuria as a presentation of metastatic oesophageal carcinoma

Haematuria is a classical symptom of urological disease often signifying a primary bladder cancer. Rarely, however, the presence of blood in the urine can be due to secondary spread of tumours into the bladder from distant sites. Notably this has been reported to occur in breast cancer, malignant melanoma and gastric cancers. Haematuria due to spread from a primary oesophageal cancer to the bladder has never been reported. We present a case of haematuria confirmed histologically to be due to metastases from a primary oesophageal tumour. Oesophageal cancer is capable of spread to all three neighbouring compartments (abdomen, chest and neck) and therefore has the potential to spread to unusual sites. Clinicians should always carefully regard haematuria in a patient previously treated for cancer and retain a high index of suspicion for distant metastases as being the cause.