ABCB1 and BMI1 mRNA expression in patients with chronic myeloid leukemia: impact on imatinib efficacy

BACKGROUND: ATP-binding cassette transporters are important in the mechanism of multidrug resistance. ABCB1 displays a high affinity for imatinib. BMI1 is a polycomb group protein thought to be overexpressed in leukemic cells. METHODS: This study was conducted to investigate the prognostic value of ABCB1 and BMI1 expressions in chronic myeloid leukemia (CML). Expression levels were measured in 81 patients newly diagnosed with CML and 20 healthy controls by real time reverse transcription- PCR. RESULTS: The ABCB1 expression levels did not differ between patients with CML and controls. Low ABCB1 mRNA levels were observed in patients who achieved an optimal response compared to suboptimal and resistant cases (P=0.005). Non-responders showed the highest ABCB1 levels. ABCB1 expression did not affect the progression-free survival (PFS) of patients. BMI1 expression was higher in patients than that in controls (P=0.001). Patients in advanced phases expressed higher levels of BMI1 than those in the chronic phase (P=0.004). High BMI1 expression was associated with a shorter PFS. CONCLUSION: ABCB1 mRNA expression may serve as a predictor of the optimal response to imatinib treatment in patients with CML. BMI1 expression was higher in the accelerated and blastic crisis phases of CML and associated with a shorter PFS.

The prognostic value of glucocorticoid receptors for adult acute lymphoblastic leukemia

BACKGROUND: Therapeutic protocols used in adult acute lymphoblastic leukemia (ALL) are widely variable, and glucocorticoids (GCs) are essential components in ALL treatment. Therefore, this study aimed to evaluate the distribution of prominent glucocorticoid receptor (GR) gene polymorphic variants among adult ALL patients. We also investigated the association between GR messenger ribonucleic acid (mRNA) isoform expressions and the response to chemotherapy. METHODS: Fifty-two newly diagnosed Philadelphia-negative adult ALL patients and 30 healthy control subjects were enrolled in this study. Genotyping was carried out using a polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. GR mRNA isoform expressions were assayed by quantitative real-time PCR. RESULTS: ALL patients in this study had a median age of 34 years (range, 18-75). GRalpha expression was associated with complete remission (P=0.03), while GRgamma mRNA expression was significantly higher in GC resistant patients (P=0.032) and in non-responders (P=0.019). However, there were no significant associations with GC resistance. The BclI polymorphic variant of the GR gene was the most frequent in adult ALL patients and was not associated with the GC response. Both higher GRalpha expression and lower GRgamma expression were associated with achievement of complete remission, while higher GRgamma expression was associated with GC-resistance. CONCLUSION: Our data suggest that the level of GR isoform expression may be useful in predicting GC response, achievement of complete remission, and better event-free survival in ALL patients. However, further evaluation with a larger cohort of patients is warranted.

Synthesis, spectral characterization and antimicrobial activity of copper [II] complexes with 2,3-dihydroxyquinoxaline and their adducts with some heterocyclic Nitrogen donors

The reaction of 2,3-dihydroxyquinoxaline, H2dhq with Cu [Ac]2-H2O or CuX2-H2o [X = Cl or Br] gave complexes of stoichiometry [[Hdhq [2]Cu] and [[H2dhq]2CuX2], respectively. Mixed-ligand complexes [[Hdhq[2]CuL[2]] [L = pyridine, 3-picoIine, 4-pincoline, imidazole, 1-methylimidazole or 1,2-dimethylimidazole were also prepared. The complexes were characterized by elemental analyses as well as by infrared, electronic and ESR spectral studies. The IR data showed that H[2]dhq acted as a monobasic or neutral bidentate ligand bonded to copper[II] via enolate and ketoamide-O atoms in [[H[2]dhq[2]Cu] and via ketoamide-O atoms in [[H2dhq]2CuX2]. The electronic spectra indicated that both [[H2dhq]2CuX2] and [[Hdhq]2CuL2] complexes possessed distorted octahedral structures containing CuO[4]X2 and CuO4N2 chromophores, respectively. On the other hand, [[Hdhq[2]Cu] was associated with a square planar structure having a CuO[4] chromophore. ESR studies revealed that metal-ligand covalency increased upon bonding of nitrogen donors to copper [II]. Study of the antimicrobial activity showed that introduction of axial N-donors significantly increased the efficiency of inhibition

Study of some parameters of endothelial dysfunction and coagulopathies in schistosomal cor pulmonale patients

Shistosomal cor-pulmonale [SCP] is one of the most important causes of vascular cor-pulmonale in Egypt. The aim of the work was to study the role of endothelial coagulation interaction in the initiation and /or progression of SCP. The study was carried out on 26 male schistosomal patients. They were divided into 2 groups: Group I [GI]: 16 patients with SCP. Group II [GII]: 10 schistosomal non-corpulmonale patients of matched age. All patients were subjected to cardiac Echo-Doppler study and right heart catheterization for measurement of blood pressure in the pulmonary artery and right ventricle. Blood samples obtained from the pulmonary artery were utilized for measurement of: - Fibrinogen. - vWF activity.-Platelet aggregation index.- Fibrin monomers. vWF activity was significantly higher in GI[173.4 +/- 58%] compared with GII [109.8 +/- 17.3%] and there was a statistically significant positive correlation between vWF activity and systolic pulmonary artery pressure [SPAP] [r = 0.654],P = 0.006] and a statistically significant negative correlation between vWF activity and platelet aggregation index [r = -0.6557,P 0.006]. Fibrinogen level was found to be significantly lower in GI [149 +/- 25.2 mg%] compared with GII [269 +/- 36.3 mg%]. Several signs indicating intra-vascular coagulopathy have been observed in GI since platelet aggregation index in that group [0.69 +/- 0.09] was markedly lower than its value in GII [0.95 +/- 0.02], signifying the increased propensity for thrombosis inside the pulmonary artery in GI compared with GII. Moreover, fibrin monomers have been detected in the pulmonary artery in 87% of cases of GI while they were not detected in any case in GII. We conclude that endothelial dysfunction and local coagulopathy in lung vasculature of SCP patients are important to proggression, if not initiation, of pulmonary hypertension

Effect of honey on tracheobronchial tree of adult male guinea pigs

The effect of honey on the bronchoconstriction induced by histamine [0.5%] and acetylcholine [4%] aerosols in normal conscious guinea pigs, as well as its antianaphylactic effect on sensitized guinea pigs exposed to the antigen [5% ovalbumin aerosol] have been evaluated. Pretreatment with honey [3 g/kg] prolonged the preconvulsive time of normal conscious guinea pigs exposed to histamine, acetylcholine aerosols, or sensitized guinea pigs exposed to the antigen [5% ovalbumin] aerosol. The effect in the latter one is better than the first two types. This denoted that honey can be used for treatment of bronchial asthma due to its antagonistic effect to hypersensitivity reactions

Effect of pretreatment with labetalol on gastric secretions altered by ethanol administration

The present work was carried out on 80 pylorus ligated rats to study the effects of oral 50% ethanol [1 ml/150 g rat] for a period of 3 hours on gastric secretion and the effect of pre-treatment with graded doses of labetalol administered by intraperitoneal [IP] route before oral ethanol on the same parameters. The collected gastric juice was analyzed for volume [ml], titratable acidity [Meq/l], total acid output [Meq/h], pepsin concentration [mg/ml] and glycoprotein content [mg hexose/ml]

use of soft laser for the treatment of lymphoepithelial lesion of the parotid gland, [Mikulicz's disease]

In the present-study, a case of lymphoepithelial lesion of the parotid gland was reported in which there was a symptomatic bilateral parotid gland enlargement, the histopathological features shows epimyoepithelial cell islands and marked lymphocytic infiltration. There was severe xerostomia with difficulty in deglutition. Using the recent diagnostic aids a trial was made to establish a definite criteria for this disease. Soft laser was used for the treatment of this case which resulted in marked decrease of the swelling and improvement of xerostomia to certain extent identified by easier swallowing of food and decreaseing of the daily water intake. Post treatment true cut needle biobsy for the left parotid showed disappearance of the tumor cells with marked regeneration of the glandular tissues, and the diagnosis was nonspecific granulation tissues

Porous hydroxyapatite blocks and ceramic as a bone substitute in bone defects

Porous hydroxyapatite blocks and ceramic were used to obliterate induced bone cavities in the femur of rats. The study demonstrated that PHA blocks give much better results than cermic material when used as a bone substiture

Comparative study between interpore 200TM porous hydroxyapatite granules and ceramic in induced bone defects in albino rats

The use of porous hydroxyapatite granules and ceramic in bony defects induced in the lower end of the femur of albino rats resulted in good healing with bone formation around and in the pores of hydroxyapatite granules. On the other hand bony defects obliterated with ceramic showed a slower rate of healing and less bone formation, around the material

Porous hydroxyapatite blocks and granules in bony defects in rats

The use of porous hydroxyapatite granules and blocks in obliteration of induced bony defects in rats showed superior results in case of the use of PHA granules in comparison with the results in case of the use of PHA blocks

Combined validity of minimal cardiac transit time and gated blood pool evaluation of the left ventricular function in schistosomiasis

The minimal cardiac transit time [MTT] and left ventricular ejection fraction percent [EF%] were measured for 25 patients with schistosomal hepatic fibrosis [SHF], 15 of them had also schistosomal cor pulmonale [SCP] in addition. The MTT was prolonged in patients with SCP in whom the EF% was significantly reduced at rest and after exercise than the patients without SCP [P <0.01]. These changes indicated that the pumping function of left ventricle is disturbed in patients with SCP. The possibility of schistosomal cardiomyopathy has been discussed

Cardiac performance in hypothyroidism

Study of the cardiac performance in ten patients suffering from hypothyroidism was done by systolic time intervals [STI]. STI measurements were repeated after triiodothyronine [T[3]] administration for 2 weeks and 4 weeks. Prolongation of the corrected electromechanical systole [QS[2 I]], pre-ejection period index [PEPI] and isovolumic contraction period [IVCP] was observed. Also the impairment of left ventricular function was evidenced by prolongation of the PEP/LVET ratio. Insignificant changes in these measurements were found after T[3] therapy for 2 weeks, while after 4 weeks correction of these intervals was observed. The significance of these results was discussed