Efficacy And Tolerability Of Oral Iron Chelator, Deferasirox.

BACKGROUND: Thalassemia major is the severe form of ß thalassemia characterized by severe anaemia, hepatosplenomegaly and facioskeletal changes due to increased haemolysis of defective red blood cells. In iron overload states, high levels of iron exceed the iron-carrying capacity of transferrin within the plasma, leading to the formation of nontransferrin-bound iron form. These nontransferrin-bound iron forms can be taken up into cells, including liver, heart, and endocrine cells leading to organ damage. To prevent complications associated with hemosiderosis, iron chelation therapy remains one of the main objectives of clinical management of the patients affected by Thalassemia Major. METHODS: Thirty-seven patients were enrolled using non randomized convenience sampling technique after the written consent from patients. Patients age 2-30 years were enrolled in this study. Serum Ferritin, ALT, Serum Creatinine were checked at the start of the study, 3 months, 6months and then at the end of the study, i.e., at 9 months of the commencement of the study. They were also assessed for other side effects pertaining to oral tolerability of the drug like vomiting, nausea, GI upset, diarrhoea, urinary complaints or any other subjective complaint. RESULTS: Of the 37 patients, 20 were male (54.1%) and 17 were female (45.9%). Mean age of the patients was 10.2 years (Min. 3 years, Max 21 years). The average serum Ferritin at baseline was noted as 3440 which increased after a period of 3 months, 6 months and 9 months with average of 3359, 3677 and 4394 respectively. After the period of 9 months largest 95% confidence interval of serum Ferritin levels was observed in the range of 3420.17 to 5368.63. In our study, 17 patients required alternative chelation (46%). These patients needed IV Deferioxamine because of the rising trend of Serum Ferritin after the study. CONCLUSIONS: From the results of our study, we infer that oral Deferasirox is not an effective iron chelator. If the patients are taking oral deferasirox, their Serum Ferritin should be checked 3 monthlies. The drug is effective only in maintaining Serum Ferritin levels with levels less than 1500ng/ml. Intravenous Deferioxamine still should be preferred over oral iron chelators for effective control of iron overload and its complications.

Potential Angiotensin Converting Enzyme Inhibitors from Moringa oleifera.

BACKGROUND: Hypertension is the chronic medical condition and it affected billions of people worldwide. Natural medicines are the main alternatives to treatment for a majority of people suffering from hypertension. Niazicin-A, Niazimin-A, and Niaziminin-B compounds from Moringa oleifera ethanolic leave extract were reported to have potent antihypertensive activity. OBJECTIVE: These compounds were targeted with Angiotensin-converting enzyme [ACE] which is one of the main regulatory enzymes of the renin-angiotensin system. METHODS: Protein-ligand docking of these compounds with [ACE] [both domain N and C] was conceded out through Autodock vina and visualization was done by chimera. Pharmacokinetics study of these compounds was predicted by ADME-Toxicity Prediction. RESULTS: Niazicin-A, Niazimin-A, and Niaziminin-B showed high binding affinity with ACE and partially blocked the active sites of the enzyme. Niazicin-A, Niazimin-A and Niaziminin-B showed the estimated free binding energy of -7.6kcal/mol kcal/mol, -8.8kcal/mol and -8.0kcal/mol respectively with C-domain of ACE and -7.9kcal/mol, -8.5kcal/mol and -7.7kcal/mol respectively with N-domain of ACE. The compounds showed better binding energy with angiotensinconverting enzyme in comparison to Captopril -5.5kcal/mol and -5.6kcal/mol and Enalapril [standard] -8.4kcal/mol and -7.5kcal/mol with C and N domain, respectively. CONCLUSION: Computationally, the selected bioactive molecules have shown better binding energy to known standard drugs which have been already known for inhibition of ACE and can further act as a pharmacophore for in vitro and in vivo studies in the development of alternative medicine.

Phytochemical and Biological Activities of Pseudocalymma elegans: A False Garlic.

Evaluation of phytochemical constituents and antioxidant and antimicrobial activities of hexane (PELH), dichloromethane (PELDCM), ethyl acetate (PELEA), and MeOH (PELM) extracts of young leaves of Pseudocalymma elegans have been carried out. Moreover, extracts have also been explored for the presence of sulphur containing compounds, 1,2-dithiolane (33), diallyl disulfide (35), 3-vinyl-1,2-dithiacyclohex-5-ene (37), and diallyl trisulfide (38) responsible for the garlic like smell of P. elegans. All the extracts were found to be antioxidant and showed potent inhibition with IC50 values of 0.168 ± 0.001, 0.128 ± 0.002, 0.221 ± 0.011, and 0.054 ± 0.001, respectively, as compared to standard drugs ascorbic acid (AA) and butylated hydroxytoluene (BHT). The ethyl acetate extract (PELE) showed excellent activities against few Gram-positive and Gram-negative bacteria and some fungi as compared with standard drug ceftriaxone (3rd generation cephalosporin) and nystatin, respectively. Chemical constituents of hexane, dichloromethane, and ethyl acetate extracts were identified by gas chromatography-mass spectrometry and mass spectral library search. Over all 55 chemical constituents were first time identified from the leaves which included branched and n-hydrocarbons, fatty acids, fatty acid methyl esters, fatty alcohols, terpenes, alkaloid, vitamins, glycosides, aromatic compounds, and sulfur containing compounds. Two known chemical constituents, ursolic acid (1) and ß-amyrin (2), were also purified for the first time from the MeOH extract. To elucidate the structures of these compounds, UV, IR, EI-MS, 1 H- and 13 C-NMR spectroscopy were used.

Role of oxidative injury in affecting the foetal & placental weights on exposure to tobacco smoke.

OBJECTIVE: To investigate the role of oxidative injury in affecting foetal and placental weights in mice by exposing them to tobacco smoke with or without supplementation with antioxidants. METHODS: The randomized control trial of pregnant mice at day one of gestation was conducted at Anatomy Department CPSP Regional Center Islamabad, from March 2005 to October 2005. The mice were divided into three groups: Group C had controls, while the two other groups, groups S and SV were exposed to secondary tobacco smoke in a whole body exposure chamber with and without supplementation with vitamins respectively. At term, the animals were sacrificed and the placentae and foetuses were weighed. The average values were calculated. The means for each group were analysed and the foetal placental ratio was calculated. SPSS 17 was used for statistical analysis. RESULTS: There were 44 mice; 15(34%) each in S and SV groups, while Group C had 14(32%) mice who acted as the controls. The mean foetal weight in Group S was 0.65±0.52g which was significantly less (p<0.0001) than1.48±0.19g in Group C. The mean foetal weight in Group SV was 0.97±0.65g which was not significantly different from S (p=0.124). The mean placental weight in Group S was 0.16±0.02g which was significantly less than 0.21±0.05gin Group C (p=0.014). In Group SV it was significantly more than Group S (p<0.0001). The ratio of mean foetal and mean placental weights in the groups C, S and SV were 7.05, 3.92 and4.41 respectively. CONCLUSIONS: Prenatal exposure to tobacco smoke decreased the mean foetal and placental weights and the foetal-placental ratio. This may partly be attributed to oxidative injury induced by free radicals in the tobacco smoke as it is prevented to some extent by simultaneous administration of antioxidants.