Volume 12, Issue 1, Summer and Autumn 2012, Page 1-85

Evaluation of CA 15-3, Her-2/neu and estrogen/progesterone status in breast cancer patients treated by surgical removal and chemotherapy

Taha H Taha Al-siagh; Shahbaa A Al-bayati; Faris A Ahmed

Iraqi Journal of Pharmacy, 2012, Volume 12, Issue 1, Pages 1-7
DOI: 10.33899/iphr.2012.62338

Objective: This study was conducted to evaluate serum CA 15-3 in breast cancer patients after surgery and chemotherapy. The relationship between serum CA 15-3 and Her-2/neu, estrogen, or progesterone receptors were also studied in the breast cancer patients.
Patients and methods: This study was conducted at Al-Jammhori Teaching Hospital, and Al-Zahrawi Private Hospital, Mosul, Iraq, during the period from January to Jun 2011. Fifty breast cancer women diagnosed by using triple assessments by a surgeon (history examination, ultrasound mammography, and fine needle aspiration cytology) were included in the study. Blood samples (5 mL) were taken from the patients and analyzed for serum CA 15-3 by monoclonal antibody technique. The blood samples were taken from the patients a week before and after one week of the operation and other blood samples were taken after two weeks of the first cycle of chemotherapy treatment. Combination therapy of 5-fluorouracil, epirubicin, cyclophosphamide, for three cycles every 21 days, was given to the patients, followed by three cycles docytaxil every 21 days. Samples from the tumor on paraffin sections taken from the patients were analyzed for Her-2/neu, estrogen and progesterone receptors by immunochemical methods.
Results: Serum CA 15-3 was significantly decreased by 54% (p ≤ 0.001) after surgical removal of the cancer compared with results before surgery. Chemotherapy of the patients further decreased serum CA 15-3 significantly by 78% (p ≤ 0.001) compared with the results before surgery. CA 15-3 and tumor size in positive Her-2/neu patients were significantly higher than in negative Her-2/neu patients. However, serum CA 15-3 and tumor size in positive estrogen patients were significantly lower than in negative estrogen patients. In progesterone positive patient's serum CA 15-3 was only significantly (p ≤ 0.001) lower than in the negative progesterone patients. Mean ages was significantly (p ≤ 0.001) higher in positive Her-2/neu patients than in negative Her-2/neu patients. However, mean ages was significantly (p ≤ 0.001) higher in positive estrogen and progesterone patients than in negative receptors. Metastasis occurred in 39 patients (78 %) out of the studied patients. Negative significant correlation was noticed between Her 2/neu and estrogen receptors (r= - 0.745, p ≤ 0.001). Negative significant correlation was also noticed between Her 2/neu and progesterone receptors (r= - 0.786, p ≤ 0.001). Weak but significant correlation was found between serum CA 15-3 and tumor size (r= 0.281, p≤ 0.05).
Conclusion: CA 15-3 and Her 2/neu are useful tumor markers for diagnosis of breast cancer in the treatment through surgery and chemotherapy. The co-expression between hormonal and Her-2/neu receptors is negative. The need for more sensitive tumor markers is still wanted.

Evaluation of combined biochemical markers in the diagnosis of acute coronary syndrome in Nineveh governorate

Samir B Al-mukhtar; Akram J Ahmad

Iraqi Journal of Pharmacy, 2012, Volume 12, Issue 1, Pages 8-19
DOI: 10.33899/iphr.2012.62339

Objective: To evaluate the importance of combination of biochemical markers in patients with Acute Coronary Syndrome (ACS) and to determine the optimal biochemical strategy for highly sensitive, early diagnosis of myocardial injury.
Patients and methods: This study was carried out in coronary care unit in Ibn- Sena Teaching Hospital in Mosul city from January to November, 2008. Two hundred and forty nine patients with (ACS) presented with chest pain and one hundred and eleven apparently healthy subjects. Four cardiac markers Creatine Kinase (CK) and Creatine Kinase-MB (CK-MB) activities (markers of necrosis), myoglobin (marker of muscle injury), and troponin I (marker of necrosis) were estimated in addition to CK-MB index. The collected data were analyzed by chi square, unpaired t-test and analysis of variance (ANOVA). Receiver Operating Characteristics (ROC) analysis was used to assess the role of selected parameters in the diagnosis of ACS and to determine optimal cut-off values for all biochemical markers.
Results: The optimal cut-off value of each of 5 parameters with reasonable validity were used to define single test criteria. The serum troponin I was with highest validity among other parameters. The serum troponin I was used in combination with each of the remaining 4 criteria and the test performance was assessed. All combinations were associated with higher specificity than that of serum troponin I alone. However, the accuracy of serum troponin I alone 94.0% was higher than the accuracy of all other combinations.
Conclusion: The study has suggested that combining troponin I, myoglobin and CK-MB index yields satisfactory diagnostic sensitivity and thus provide valuable information for clinicians in managing Acute Coronary Syndrome (ACS).

Synthesis of new coumarin derivatives with suspected anticoagulant activity

Yasser Fakri Mustafa

Iraqi Journal of Pharmacy, 2012, Volume 12, Issue 1, Pages 20-32
DOI: 10.33899/iphr.2012.62340

Objectives: To synthesize three series of new coumarin derivatives and to screen their anticoagulant activity in rabbits in order to define in more exact terms the structural features that responsible for the anticoagulant activity of coumarins.
Methods: the first series was synthesized by esterification the 7-hydroxycoumarin with benzoic acid, salicylic acid and 5-amino salicylic acid to give derivatives I-III; the second series was synthesized by the formation of amide linkage between 6-aminocoumarin and benzoic acid, salicylic acid and 5-amino salicylic acid to give derivatives IV-VI while the third series was synthesized by esterification the coumarin-6-carboxylic acid with phenol, resorcinol and m-chlorophenol to give derivatives VII-IX.
The anticoagulant activity of these derivatives (I-IX) was investigated in rabbits via Quick's one-stage method; the initial effect of each derivative on the prothrombine time for five rabbits before and after oral administration was measured.
Results: The chemical structure of these derivatives was characterized by physical and spectroscopic techniques as FTIR, UV and 13C-NMR spectra. Depending on prothrombin time measurements, derivatives II and VIII showed a significant anticoagulant activity through increasing the prothrombine time while the other derivatives showed an insignificant anticoagulant activity.
Conclusion: This study proposed that the coumarin derivatives contained an ester linkage at position 6 or 7 separated from a hydroxyl group by short carbon side chain may show anticoagulant activity.

Effect of typical and atypical antipsychotic drugs on serum C-reactive protein and lipid profile in schizophrenic patients

Faris A Ahmed

Iraqi Journal of Pharmacy, 2012, Volume 12, Issue 1, Pages 33-40
DOI: 10.33899/iphr.2012.62341

Objectives: To assess the effect of quetiapine and fluphenazine on serum high sensitivity C-reactive protein (hs-CRP) and serum lipid profile in schizophrenic patients.
Patients and methods: The subjects comprised two groups of twenty seven newly diagnosed schizophrenic patients for each group. The first group was treated orally with quetiapine at a dose 200-500 mg/day. The second group was treated with fluphenazine intramuscularly at a dose 25 mg every 4 weeks. Twenty seven healthy volunteers were also included as a control group. The patient and the control groups were age and sex matched. The patients were diagnosed by a psychiatrist on the basis of semi-structured interview to determine DMS-IV diagnosis. Clinical symptoms were assessed in 14 of the 18 Brief individual Psychiatry Rating Scale (BPRS) items in order to measure the severity of schizophrenia. Fasting blood samples from the patients were taken for analysis before the beginning of quetiapine or fluphenazine treatment and after 8 weeks of the study. Other blood samples were taken from healthy subjects as a control group.
Results: Serum hs-CRP was significantly (p  0.01) higher in the schizophrenic patients before treated by quetiapine or fluphenazine (difference = 382.9% and 395.1% of control, respectively) than controls. The measurement of hs-CRP decreased significantly (p  0.01) after quetiapine treatment by 19.1%, while it was increased significantly (p  0.01) after fluphenazine by 12.3% compared with before treatment values. In the schizophrenic patients, serum total cholesterol (TC) and triglycerides (TG) were significantly higher (p  0.01) than controls, while high density lipoprotein cholesterol (HDL-C) was lower than controls. Quetiapine caused significant increase (p  0.01) in serum TC and TG, while serum HDL-C decreased significantly (p  0.01) compared with the results before treatment. Fluphenazine did not cause any significant change in the lipid parameters. Quetiapine treatment significantly increased (p  0.05) body mass index (BMI), whereas fluphenazine did not change BMI compared with before treatment values. Base time and after 8 weeks of quetiapine or fluphenazine treatment showed significant decrease in the score of BPRS by quetiapine and fluphenazine.
Conclusion: Quetiapine depressed CRP and caused dyslipidemia. Fluphenazine raised CRP but it had no effect on lipid profile.

Measurement of plasma cholinesterase activity in field workers

Ansam Naji Aboud Al-Haseni; Basil Mohammed Yahya

Iraqi Journal of Pharmacy, 2012, Volume 12, Issue 1, Pages 41-47
DOI: 10.33899/iphr.2012.62342

Objectives: Measurement of cholinesterase (ChE) activity is considered as an important diagnostic tool in the cases of human poisoning with organophosphate (OP) and carbamate insecticides.
Patients and methods: One hundred and seventy four subjects working in different fields and exposed to OP and carbamate compounds were conducted in this work plus fifty apparently healthy volunteers, who were neither exposed to OP and carbamate insecticides nor taken any drug during the course of this study (control group). Subjects were categorized into three groups according to the place of their work. An electrometric method was used for the measurement of blood ChE activity.
Results: The results showed significant differences at p < 0.05 of ChE activity in the 3 groups in comparison with the control. Also the relationship between ChE activities concerning the age of the subjects and the duration of exposure in the market group was significantly different at p < 0.05.
Conclusion: The electrometric method is simple and efficient for multiple samples and field conditions and offers a lower cost, also it is suitable for monitoring human exposure to OP and carbamate insecticides

Alleviation of cisplatin-induced nephrotoxicity in rats by aqueous extract of Salvia officinalis leaves

Kawa Dizaye

Iraqi Journal of Pharmacy, 2012, Volume 12, Issue 1, Pages 48-55
DOI: 10.33899/iphr.2012.62343

Objectives: To evaluate the protective effects of the aqueous extract of Salvia officinalis leaves against nephrotoxicity induced by cisplatin in rats.
Methods: Albino rats were divided into three groups, each group consist of six rats. Group I treated with vehicle (distilled water) was kept as a control. Group II injected with a single dose of cisplatin (12 mg/kg body weight; i.p.). Rats in Groups III were received a single daily dose of aqueous extract of S. officinalis 100 mg/kg (P.O.), for 7 days. On the seventh day, cisplatin (12 mg/kg body weight; i.p. was administered half an hour after the last dose of the plant extract. The rats in all groups were sacrificed 72 h after treatment. Renal injury was assessed using serum biochemical markers (creatinine and urea).
Malondialdehyde (MDA) concentration was measured as a marker of lipid peroxidation.The renoprotecive activity of S. officinalis was supported by histo- pathological studies of the kidney.
Results: Aqueous extract of S officinalis leaves significantly protected rat kidneys from cisplatin-induced histopathological changes. This extract also normalized cispaltin
induced increases in serum creatinine and blood urea. In vitro studies revealed that the S officinalis leaf extract possessed significant oxidative radical scavenging activities.
Conclusion: Both biochemical findings and histopathological evidence showed the renoprotective potential of aqueous extract of S. officinalis leaves against cisplatin-induced oxidative stress and renal dysfunction in rats.

Effects of valsartan vs captopril on some renal function tests in hypertensive patients

Shamil Hashim Othman

Iraqi Journal of Pharmacy, 2012, Volume 12, Issue 1, Pages 56-64
DOI: 10.33899/iphr.2012.62344

Objectives: To investigate the effects of valsartan and captopril on some renal function tests (RFTs) in patients with essential hypertension.
Patients and methods: A total of 40 patients with stage I essential hypertension were recruited and investigated for RFTs which include, blood urea, serum creatinine, creatinine clearance, serum sodium and serum potassium. The patients were divided into 2 groups, namely the valsartan group which consisted of 20 patients and the captopril group which consisted of 20 patients. The patient groups were followed- up for 8 weeks during which RFTs were measured before starting therapies and at the end of the follow-up period using commercially available kits. The patient groups were compared with a control group consisted of 30 apparently healthy subjects.
Results: The RFTs at baseline in both patient groups were found elevated as compared to the control group (p < 0.001), except for serum potassium concentration which was comparable . The RFTs in patient groups were comparable before and after therapies.
Conclusion: The use of valsartan and captopril for 8 weeks in hypertensive patients has no adverse effects on RFTs.

Modified high performance liquid chromatographic method for the identification of chlordiazepoxide in animal blood

Zena Sattam Hamad; Basil Mohammed Yahya

Iraqi Journal of Pharmacy, 2012, Volume 12, Issue 1, Pages 65-74
DOI: 10.33899/iphr.2012.62345

Objective: A method for simultaneous determination of chlordiazepoxide in rat plasma using liquid-liquid extraction followed by high performance liquid chromatography (HPLC) is described.
Methods: The analytes were separated employing a LC-18 column (250mm×4.6mm,5µm) at ambient temperature using methanol and water (60 : 40 v/v) as a mobile phase at a flow rate 1.2 ml/min. Ultra violet (UV) detection was carried out at 254 nm. Employing liquid-liquid extraction (LLE), the best conditions were achieved with the extraction of 0.5 ml plasma using 7.5 ml deionized water, 0.5ml of 0.1M NaOH and 2.5 ml diethyl ether, the mixture was shaken for 15 min, centrifuged, and an aliquot of the ether phase evaporated off in a water bath at 30 °C. The residue was reconstituted with the mobile phase 50 µl followed by HPLC analysis.
Results and conclution: This method was validated for specificity and linearity with excellent correlation coefficient (r=0.99) showed their suitable applicability in order to examine chlordiazepoxide in rat plasma.

Facial visible spectrophotometric determination of metformin hydrochloride in glucosam tablets and industrial waste water: Application to content uniformity testing

Nief Rahman Ahmad

Iraqi Journal of Pharmacy, 2012, Volume 12, Issue 1, Pages 75-85
DOI: 10.33899/iphr.2012.62346

Objectives: To determine simple, accurate and highly sensitive spectrophotometric method for determination metformin hydrochloride in pharmaceutical preparations and in industrial waste water sample.
Materials and Method: The method is based on the oxidation of metformin by a known excess of sodium hypochlorite in alkaline medium.
Results: Formation of a yellow-colored chromophore having maximum absorbance at 385nm. Molar absorptivity was found to be 2 × 104 L.mol-1.cm-1. Beer’s law is obeyed in the concentration range of 0.5-4 µg .ml-1, relative standard deviation (RSD) is better than ±1.8 (n =10) .The limits of detection and quantitation are 0.083 and 0.25 µg .mL-1, respectively. The method is applied successfully to determination of metformin pharmaceutical formulation (tablets).The common excipients do not interfere with the proposed method. A statistical comparison of these results with those of official method using t and F values at 95% confidence level shows good agreements and indicated no significant difference in the precision, and the present method has good validity.
Conclusion: The proposed method can be used as a routine quality control and content uniformity tests for determination of metformin in pure form, tablet formulations and industrial waste water sample.