Effects of CMF and MET on glutamate and dopamine levels in the brain, and their impact on cognitive function.

OBJECTIVE: Chemotherapy can cause cognitive impairment in cancer survivors. CMF, the combination of cyclophosphamide (CYP), methotrexate (MTX), and 5-fluorouracil (5-FU), is employed for the treatment of several types of cancers, such as metastatic breast cancer. Metformin (MET) is an antidiabetic medication used to treat type 2 diabetes that can reportedly alleviate some toxic effects. In the current study, we investigated the ability of MET to alleviate the effects of CMF in neuronal toxicity. MATERIALS AND METHODS: Rats were treated with two doses of CMF (intraperitoneal injection) and MET (in the daily drinking water). Rats were subjected to fear conditioning memory tests to evaluate memory function following treatment, and brain samples were collected and homogenized using neuronal lysis buffer for assessment of glutamate and dopamine levels by high-performance liquid chromatography (HPLC). RESULTS: Fear conditioning memory tests revealed a significant reduction in memory function in CMF and CMF+MET groups vs. controls, but no significant change in MET groups vs. controls was detected. Similarly, CMF and CMF+MET groups revealed a significant increase in glutamate and dopamine levels in the brain of MET, CMF, and MET+CMF groups vs. controls based on HPLC results. In addition, although glutamate and dopamine levels were increased, levels varied between groups, with highest levels in the CMF+MET group. CONCLUSIONS: Our results demonstrate that cognitive impairment in CMF and CMF+MET groups could result from increased glutamate and dopamine levels in the brain, leading to brain toxicity and failure of MET to alleviate the toxic effects of CMF.

Co-administration of imipramine and doxorubicin reduces the survival rate and body weight of mice.

OBJECTIVE: Doxorubicin (DOX) is a chemotherapeutic agent widely used to treat cancers, particularly breast cancer. DOX has side effects, including cardiotoxicity, hepatotoxicity, and nephrotoxicity. Imipramine is an antidepressant that increases the release of neurotransmitters. This study aimed to investigate the effect of co-administration of imipramine and DOX on DOX-induced toxicity. MATERIALS AND METHODS: Forty female mice (10-12-weeks-old, 30-38 g) were divided into four groups (n = 10 per group). The animals in the control group received a single-dose saline injection. The animals in the DOX group received a single dose of DOX (20 mg/kg) by intraperitoneal (i.p.) injection. The animals in the imipramine group received the drug daily in their drinking water (0.13 mg/mL) for 9 days, starting 1 day before the DOX injection received by the DOX group. The animals in the combination group (DOX+imipramine) received a single dose of DOX (20 mg/kg, i.p. injection), and a daily dose of imipramine in their drinking water (0.13 mg/mL) for 9 days starting 1 day before the DOX injection. The animals were observed daily to record mortality, and their body weights were recorded every alternate day. RESULTS: DOX treatment increased the rate of mortality compared with that for control animals. Imipramine co-administration with DOX increased the rate of mortality significantly (p < 0.05) compared with DOX treatment alone. The mortality rate in both the control and imipramine-treatment groups was zero. DOX co-administered with imipramine resulted in significantly reduced body weight compared with control animals. CONCLUSIONS: The combination of DOX and imipramine reduced the survival rate of female mice, suggesting that imipramine increases the toxic effects of DOX.

Ameliorative effect of metformin on cyclophosphamide-induced memory impairment in mice.

OBJECTIVE: Cyclophosphamide (CYP) is a chemotherapeutic agent that is widely used as an adjuvant cancer treatment. Unfortunately, this drug is associated with secondary side effects, including cognitive impairment up to 70% of cancer survivors. The mechanism of this memory impairment is unclear. Thus, to understand the cognitive impairments caused by this chemotherapeutic agent, a clinically relevant dose to cancer treatment was used in mice to establish the chemobrain models, and the spatial memory of these mice was assessed using multiple behavior tests. In addition, metformin (MET) is widely used as an anti-diabetic drug and protects against oxidative stress and hepatotoxicity. Thus, this study tested the protective effects of MET in the chemobrain models. MATERIALS AND METHODS: Four groups of mice, which weighed about 18-30 g, were collected and divided into 4 groups: control, CYP, MET, and CYP+MET groups. A 100 mg/kg dose of CYP was administered intraperitoneal (on alternate days) for a total of 4 doses. MET was dissolved in the mice's drinking water bottles at a 5 mg/ml concentration from day zero to the end of the treatment period. The mice's memory was tested using hippocampal-dependent tests, including the Y-maze, novel object recognition, and elevated plus maze tests. These tests were performed for three consecutive days after 24 h of the last dose of CYP. RESULTS: The mice treated with CYP exhibited a decline in memory function in all the behavioral test studies, and this decline was significant in the Y-maze test. However, this decline was rescued by MET administration. CONCLUSIONS: The clinically relevant model suggests that CYP treatment causes a decline in mice models spatial memory that might be improved by MET administration.

A 35 Year Old Bangladeshi Lady with Hereditary Mucinous Ovarian Cancer, Complicated with Omental Metastasis.

Approximately 80% ovarian tumors are benign, and these arise mostly in young adult females. Malignant tumors are more prevalent in ageing women, between the ages of 45-65 years. Mucinous ovarian cancer represents about 5% of epithelial ovarian cancers (EOC). We have reported a case of mucinous cystadenocarcinoma in 35-year-old lady with metastasis to momentum. Imaging (Radiograph & CT scan) studies showed a large right sided pelvic mass with probable origin in the right ovary. Cancer antigen-125 was elevated, while carcinoembrionic antigen and alpha-fetoprotein were normal. Mutational profiles shown distinct finding, as KRAS mutations positive nevertheless p53 and BRCA mutations are absent. She had undergone total abdominal hysterectomy with bilateral salphingo-oopherectomy along with pelvic dissection for removal of lymph nodes at the age of 35. She was given 3 cycles of chemotherapy with cisplatin and paclitaxel. To the best of our knowledge, this is the one of the little cases of ovarian mucinous cystadenocarcinoma being reported at a relatively young age and the first case being reported from Bangladesh.

Beta voxel S values for internal emitter dosimetry.

Monte Carlo volume integration of dose point kernels was used for calculating voxel S values of beta emissions of radionuclides of interest for internal radiotherapy. The method was verified by comparing our results with others derived from Monte Carlo radiation transport simulation. The algorithm has been implemented in a C++ program that can be used by any laboratory to calculate voxel S values of beta emissions from tabulated dose point kernels and for any combination of pixel edges and the thickness of SPECT and PET images without the complexity and expertise needed for direct Monte Carlo radiation transport simulations.