Gamma-linolenic acid therapy of human gliomas

OBJECTIVES: We investigated the effect of intratumoral administration of gamma-linolenic acid (GLA) in human gliomas. METHODS: We evaluated the effect of the administration of 1 mg of GLA for 7 d via a cerebral reservoir placed into the tumor bed or by direct intratumoral delivery in nine patients who had grade 4 disease and recurrent glioma after surgery, radiation, or chemotherapy. RESULTS: There was some, but not dramatic, improvement in patients' survival. No significant prolongation of life span was expected considering the advanced nature of the disease. Nevertheless, it was encouraging that GLA produced no significant side effects in any patient. Regression of the cerebral gliomas was visualized on computed tomography and magnetic resonance imaging. CONCLUSIONS: Based on results of the present and previous studies, we believe that GLA is a safe antitumor agent and that higher doses of GLA should be investigated in future studies.     

Molecular characterization of new melanoma cell lines from C3H mice induced by ethanol plus ultraviolet radiation

A major obstacle in understanding the etiology of malignant melanoma is the lack of mouse models and transplantable cell lines. We have recently developed a model of primary melanoma in C3H mice induced by ethanol and UV light. The present study characterizes three cell lines, SM190.2, SM190.626, and SD0302, derived from two melanomas produced in the dorsal skin of two C3H mice treated thrice weekly for 28-33 weeks with UV radiation and ethanol. In both tumors, the N-ras oncogene was mutated. Tumor SM190 lacked exon 2 of the p16(INK4a) tumor suppressor gene. Cell line SM190.2, which was derived from tumor SM190, produced pigmented tumors when transplanted into syngeneic severe combined immunodeficient mice and normal mice. None of the cell lines produced metastases. All three cell lines were highly aneuploid, even at low passage numbers. SM190.2 and SD0302 cells contained an interstitial deletion in the long arm of chromosome 4, where the p16(INK4a) gene resides, and SM190.2 had an additional segment in chromosome 6. The third cell line, SM190.626, had three consistent Robertsonian translocation markers involving chromosomes 7, 14, and 17. The translocation involving mouse chromosome 14 may prove especially valuable because translocations in this chromosome are associated with metastatic behavior. These reagents will provide opportunities to search for new tumor suppressor genes that may contribute to the growth and metastasis of primary melanoma.     

Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer

Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human blood lymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma.     

Mid latency and slow vertex responses during pregnancy

Central auditory pathways picked up electro-physiologically as mid latency responses (MLRs) and slow vertex responses (SVRs) have been studied least in women during their critical periods of life although auditory brainstem responses (ABRs) have been studied by many researchers. In the present study MLRs and SVRs were recorded in 20 pregnant women of age group 18-28 years. Their period of gestation ranged between 26-40 weeks and pregnancy had been uneventful and normal. MLRs and SVRs were recorded from Cz-A1 and Cz-A2 positions with alternating 90 dB sound pressure click stimuli delivered at 5 Hz and 0.5 Hz respectively. 256 stimuli for mid-latency and 64 stimuli for slow vertex responses were averaged and analyzed. Different waves of these auditory evoked responses were compared with 20 age matched non-pregnant females. The data obtained was analyzed for each variable by using unpaired student's T test. Present study did not reveal any difference in MLR waves during pregnancy when compared with the non-pregnant females whereas all the SVR waves were found to be significantly delayed in pregnant females. As SVR generators are found in different cortical areas, it can be said that auditory information processing at the higher centers is slow during pregnancy which in turn could be due to elevated levels of sex hormones specially estrogen and progesterone during pregnancy.     

A model to aid in the prediction of discharge location for stroke rehabilitation patients

OBJECTIVE: To determine which demographic and medical factors recorded on admission to a rehabilitation unit best predict discharge accommodation outcomes. DESIGN: Retrospective chart review. SETTING: Inpatient rehabilitation unit in an academic hospital in southwestern Ontario, Canada. PARTICIPANTS: One hundred four stroke patients (54 women, 50 men; mean age, 72.0y) admitted to the rehabilitation unit over a 4-year period. INTERVENTIONS: All patients underwent evaluations by the physical therapy, occupational therapy, social work, speech pathology, and psychology departments. Patients were divided into 2 groups: (1) no change in premorbid accommodation and (2) change in premorbid accommodation. MAIN OUTCOME MEASURES: Demographic, clinical, and housing information (premorbid, discharge) and functional data (FIM trade mark instrument, Chedoke-McMaster Stroke Assessment [CMSA] Impairment Inventory, Berg Balance Scale [BBS]) were recorded for each patient. RESULTS: Of 104 patients, 24 were discharged with a change in premorbid accommodation. Change in discharge location was significantly associated with age, gender, and the presence of premorbid social support (P<.01), but not with type of premorbid living arrangement. Statistically significant differences were noted between total FIM scores (P<.001), BBS scores (P<.001), and the postural component of the CMSA Impairment Inventory (P<.03). A logistic regression model, predicting 67% of the variance, was created to predict discharge accommodations. CONCLUSIONS: Patients admitted to the rehabilitation unit can be scored to obtain their predicted chance of being discharged with a change from their premorbid accommodations. The equation is relatively easy to calculate and is based on data that are commonly collected in rehabilitation.     

Interactive and delayed effects of pyridostigmine and physical stress on biochemical and histological changes in peripheral tissues of mice

Gulf War veterans were taking pyridostigmine orally against possible exposure to nerve agents as well as being under physical stress. This study was designed to investigate the delayed effects of pyridostigmine and treadmill exercise on cholinesterase activity, lipid peroxidation and histology of peripheral tissues of mice. Male NIH Swiss mice were divided into four groups of 15 animals each and treated as follows: sedentary control; exercise training for 10 weeks; pyridostigmine (1.2 mg kg(-1), p.o.) for 2 weeks during weeks 5 and 6; and pyridostigmine plus exercise training. The mice were sacrificed 24 h after the last exercise, and blood, triceps muscle and sciatic nerve were isolated and analyzed. The group treated with pyridostigmine alone showed decreased plasma butyrylcholinesterase (BChE) activity (87% of control), whereas pyridostigmine plus exercise significantly decreased the BChE activity (79% of control), indicating an interactive effect of the combination. Acetylcholinesterase (AChE) activity did not alter significantly in red blood cells, platelets or sciatic nerve with either of the treatments. However, AChE activity in triceps muscle decreased significantly (78% of control) in the group treated with pyridostigmine plus exercise. Creatine phosphokinase activity in plasma increased slightly (compared to control, pyridostigmine or exercise group) in mice treated with pyridostigmine plus exercise, which may be indicative of perturbation in the integrity of the skeletal muscle due to combination. However, there were no obvious histological abnormalities in the triceps muscle detected between experimental and control groups. Interaction of pyridostigmine and exercise significantly increased the concentration of the end product of lipid peroxidation (malondialdehyde) (124% of control) in triceps muscle, indicating an oxidative stress response of the combination. These results indicate that physical stress enhanced the delayed toxic effects of a subchronic oral dose of pyridostigmine primarily in the skeletal muscle of mice.