Open Access Short Research Article

Gene Expression Profiling of Triple Negative Breast Cancer Cells Treated with Afatinib

Qudus Ibrahim, Ruchi Patel, Elvis Boamah, Dolapo Ajayi, Michael Danquah

Journal of Pharmaceutical Research International, Page 1-13
DOI: 10.9734/JPRI/2017/36948

Purpose: To investigate gene expression profile changes in triple negative breast cancer cells (MDA-MB-231) treated with afatinib.

Methods: Differential expression of 84 genes commonly involved in breast cancer carcinogenesis was examined in MDA-MB-231 cells treated with afatinib (5 µM) and compared to untreated cells. Total RNA was extracted using RNeasy mini kit and subsequently assessed by real-time PCR using the Human Breast Cancer RT2 Profiler PCR Array. Relative gene expression was computed using the ΔΔCt approach and a fold change equal to or greater than 2 was considered significant.

Results: Treatment of MDA-MB-231 cells with afatinib (5 µM) for 24 h resulted in significant differential expression of several genes commonly involved in breast cancer carcinogenesis. Specifically, 33 of the 84 genes examined exhibited greater than two-fold differential expression when MDA-MB-231 cells were exposed to afatinib. Three genes (CTSD, ESR2 and ID1) were upregulated while thirty genes were downregulated in afatinib treated cells compared to control. Core analysis of differentially expressed genes using the Ingenuity Pathway Analysis (IPA) software identified five regulatory networks pertinent to cell cycle, cancer, cellular growth and proliferation. This led to phosphoinositide-3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/ERK being identified as pathways impacted by afatinib.

Conclusions: Our findings elucidate molecular targets with altered expression in MDA-MB-231 cells exposed to afatinib. Based on RT2-PCR array analysis, afatinib increased expression of key tumor suppressor genes and down-regulated expression of pivotal oncogenes. This knowledge could contribute to the design and development of effective afatinib based combination therapies for treating TNBC.

Open Access Original Research Article

Immunity and Sex Concerns on Behaviour

S. Cossy Isasi, C. Jalil, G. Giordano, J. Ortiz, J. C. Cosiansi, J. C. Muiño

Journal of Pharmaceutical Research International, Page 1-11
DOI: 10.9734/JPRI/2017/35335

Aims: To find evidence that the immune response modifies behavior by regulating sex hormones.

Study Design: Experimental transversal case control study and longitudinal experimental case control study.

Place and Duration of Study: Biochemistry and Molecular Biology Chair, School of Medicine, Medical Sciences Faculty, National University of Córdoba. 2009-2015.

Methodology: Albino Swiss mice Rockefeller strain (110) weighing 30g were assigned to two experimental designs. Transversal case control physiologic solution vs or Celtis tala pollen glycoprotein T evaluated in forced swimming test along the course of antibodies production. Similar study but cases were treated with spironolactone(S) and immunized as previous mice. Longitudinal case control study with cases and controls the same categories as the second study but followed and evaluated in FST. Climbing, swimming floating summing a total of 8 events and delated time to contact another mouse CT (seconds) were recorded. Plasma IgE and testosterone (Tt) were also measured.      

Results: Immunization with T increases the proportion of climbing in both sexes at day 7(c.male 0.42, T.male 0.72, c.female 0.28, T.female 0.68) and reverted at day 15 (c.male 0.8, T.male 0.35, c.female 0.47, T.female 0.43). Since climbing is more frequent in male we treated mice with S to determine if immunization effects were mediated by testosterone and reverted the changes triggered by C. tala (day 7, ST. males 0.22, STfemales 0.35, day 15 ST.male 0.23, ST.female 0.32). T caused a shortening of CT in males from day 7 to 15, S produced the opposite and ST was partly similar to T (T.male12.5 to 5, Smale 8,2 to 14, ST.male 11 to 4.2 in sec, T.female 2.9 to 6.2, S.female 7.8 to 17, ST.female 13 to 9.6 sec).  Plasma concentration ranges of Tt (ng/mL) were: CM 0.75-6.72, TM 31.1-58.5; STM 26-29.5; all females remained between 0.3-039.

Conclusion: The results presented in this paper support our hypothesis that immune response could modify mice FST performance by regulation of testosterone levels.

Open Access Original Research Article

Compression and Compaction Behaviour of Microcrystalline Cellulose from Sorghum and Andropogon Stalks

J. Alfa, A. Chukwu, O. K. Udeala

Journal of Pharmaceutical Research International, Page 1-11
DOI: 10.9734/JPRI/2017/37055

Sources and processing techniques could affect performance of Microcrystalline Cellulose (MCC). This study therefore evaluated the suitability of some agricultural wastes as novel sources of MCC; Sorghum Bicolour and Andropogon gayanus. The physics of compaction of the new grades of cellulose; Sorghum MCC (SOMCC) or Andropogon MCC (AMCC) was compared with Avicel PH101. The SOMCC and AMCC were isolated from mineral acid hydrolysed de-lignified α-cellulose of the plant stalks. Particle size distribution was analysed.  The carver hydraulic press was used for compaction study. Heckle plots, tensile strength, reworking potentials (RWP), disintegration and friability profiles were used as basis for assessment. The median particle size was 52.5 or 80 µm for AMCC and SOMCC with interquartile coefficient of skewness (IQCS) of 19.2 and 21.5%.respectively. Particle size fractions of 125-250 µm produced compacts with similar strength profiles. The polymer grades, AMCC, SOMCC and Avicel PH101 at fixed compression pressure of 62.4 N/mm2 exhibited similar tensile strength in the range of 2.7- 2.8 N/mm2. Heckel plot analysis showed similarity in yield pressure of 152.3 N/mm2 or 151.5 N/mm2 for Avicel PH101 and SOMCC with notable higher value in AMCC at 192.1 N/mm2.  The degree of packing achieved by the particles at low compression pressure was 1.23, 1.39 and 1.12 for SOMCC, Avicel PH101 or AMCC while the extent of particle rearrangement at initial compression vide the relative densities (DB) was in the order 0.519, 0.539 and 0.454 respectively.  The results are heavily suggestive of deformation by plastic flow mechanism for the new polymers. In ranking, the degree of compaction and consolidation of SOMCC ≈ Avicel PH101 > AMCC. The reworking potential was in the order AMCC < SOMCC ≈ Avicel PH101.

The indication is that SOMCC and AMCC could find application as excipients in the pharmaceutical and allied industries.

Open Access Original Research Article

Efficacy of Vitamin B6 on Pregnancy Outcomes: A Randomized Clinical Trial

Maryam Khodadad, Gholamreza Kheirabadi, Parvin Bahadoran

Journal of Pharmaceutical Research International, Page 1-9
DOI: 10.9734/JPRI/2017/32675

Background: Postpartum depression is a common and disabling disorder. A low level of vitamin B6 might theoretically causes symptoms of depression. The aim of this study was to investigate the effect of vitamin B6 on Pregnancy outcomes among the mothers at risk for postpartum depression during third trimester.

Methods: A single blind randomized clinical trial was conducted via using B6 and placebo on 86 at risk postpartum depression pregnant subjects at six selected health center in Isfahan, Iran with a simple random sampling method (Feb-July, 2016). The main inclusion criteria in this study was at least a risk factor of postpartum depression; evaluated by Hospital Anxiety-Depressive Scale, Social Support Appraisals Scale, Holmes and Rahe Life Change and Stress Evaluation Questioner. Data was analyzed applying SPSS20 and statistical tests (chi-square, t-test, Mann-Whitney, Fisher’s exact test).

Results: In case group after intervention mean depression score was (4.2±2.7) significantly lower than before intervention (10.4±1.4) (p<0/001) Control group mean depression score was no significant difference after (10.4±3.4) and before intervention (9.3±4.2) (p= 0.10).

Mean maternal weight gain (P=0.32), delivery type (P=0.56), infant birth weight (P=0.37), gestational age (P=0.31) were not significant difference between two groups.

Conclusion: Vitamin B6 may have a positive effect to decreasing of postpartum depression score, and no effects on another pregnancy outcome.

Open Access Original Research Article

The Effect of Creatine Supplementation with Resistance Training on the Levels of Renin and Aldosterone in Wistar Rats

Shadi Hamedi, Gholam Reza Sharifi, Marzieh Kafeshani

Journal of Pharmaceutical Research International, Page 1-7
DOI: 10.9734/JPRI/2017/36504

Objective: The aim of the present study was to compare the effect of creatine 2% and 5% supplementation with resistance training on the levels of renin and aldosterone

Methods: The 60 Wistar rats were randomly assigned to six groups (resistance training, creatine 2% and creatine 5%, resistance training plus creatine 2% supplementation, resistance training plus creatine 5% supplementation, control). The training included 8 weeks and 5 sessions a week climbing a 1-meter ladder with 26 rungs with 2-cm distances. The One – way analysis of variance (ANOVA) test was used for comparing the variables between groups and LSD test was used for pair-wise comparisons.

Results: There was no significant difference between mean differences of renin level in different groups compared to the control group. Butthere was a significant difference between mean difference of aldosterone level in creatine 5% groups and control group as well as between resistance training plus creatine 2% and creatine 5% groups (p < 0.05). Also, there was significant difference between mean difference of aldosterone level in resistance training and creatine 5% groups (p < 0.05).

Conclusion: As regard to result of the present study consumption of creatine 2% and 5% supplementation may be useful and safe for human so further studies is suggested.