Genistein induces a protective immunomodulatory effect in a mouse model of cervical cancer.

BACKGROUND: Genistein (GEN), a naturally occurring flavonoid present in soy bean, has attracted scientific interest for its possible benefits in cancer. OBJECTIVE: The potential immunomodulatory effects of genistein on the immune system and against TC-1 tumor cell line were evaluated in adult female C57BL/6 mice. METHODS: Mice were treated with GEN 10 days before to 10 days after the tumor induction. Thirty days after the last GEN treatment, lymphocyte proliferation, Lactase Dehydrogenase (LDH) cytolytic activity and cytokine secretion were analyzed in GEN and control groups. RESULTS: The results showed that ingestion of genistein significantly increased lymphocyte proliferation and LDH release. Furthermore, the treatment with genistein also caused a significant increment in interferon gamma (IFN-γ). In addition, the treatment achieved significant therapeutic effect in tumor models compared to the control group. These results indicated that the effect of GEN on tumor growth may be attributed to its effect on lymphocyte proliferation, cytolytic activity and IFN-γ production. CONCLUSION: These results demonstrate that GEN exerts an immunomodulatory effect in a mouse model of Human Papillomavirus (HPV) associated-cervical cancer.

Protection of mice by a λ-based therapeutic vaccine against cancer associated with human papillomavirus type 16.

OBJECTIVE: Human papillomavirus (HPV) oncoproteins (i.e. E6 and E7) are constitutively expressed in cervical cancer cells. The proteins are ideal targets to be used for developing therapeutic vaccines against existing HPV-associated carcinomas. To date, whole bacteriophage ('phage')-λ particles, rather than purified 'naked' DNA, have been described as highly efficient delivery vehicles for a DNA vaccine. METHODS: In this study, a safe and efficient λ-based therapeutic cancer vaccine, recombinant λ-ZAP E7 phage, was developed by inserting a HPV16 E7 gene into the Lambda ZAP® cytomegalovirus vector. λ-ZAP E7 phages were employed to immunize mice against the E7-expressing murine tumor cell line (TC-1), which is used as a tumor model in an H-2b murine system. RESULTS: The tumor-bearing mice indicated a significant inhibition of tumor growth after 3 injections of 2 × 10(12) particles of recombinant phages. Released lactate dehydrogenase, interferon-γ and granzyme B from spleen cells and lymphocyte proliferation of spleen cells, which all demonstrate the enhancement of cell-mediated immunity, suggested the phages could be a potent gene delivery system in animal models. CONCLUSION: Our results suggest the recombinant phages can be used as effective biological tools for inducing E7-specific protective immune responses. Hence, the study introduces a possible therapeutic strategy against cervical cancer and other HPV-related neoplasia.

Lipid profile in cerebrovascular accidents.

BACKGROUND: Changes in the lipid profile have been suggested as a risk factor for developing ischemic stroke. Their role in intra-cerebral hemorrhage, however, is not clear. The present study was designed to evaluate the lipid profile levels of patients who had experienced an acute stroke during the first 24-hour and to compare these levels in different patients suffering from the stroke, either hemorrhagic or ischemic, and healthy individuals. METHODS: In this cross-sectional study, 258 consecutive patients with acute stroke admitted to the neurology department of our center during September 2006 and September 2007 were studied. As for the control group, 187 apparently healthy subjects living in the same community and matched for age and sex were selected. Lipid profile was measured and compared between the three groups. RESULTS: In the patients' group, 65 suffered from hemorrhagic stroke (group 1) and the other 193 had ischemic stroke (group 2). Except for TG values, there was no significant difference among the ischemic and hemorrhagic lipid profile. Age, cholesterol, and LDL influenced the risk of developing an ischemic stroke; TG was not reported as a risk factor or a protective one. While the comparison of data retrieved from patients suffering from hemorrhagic strokes with the controls, revealed LDL as the risk factor contributing to the development of ICH whereas TG was reported as a protective factor. CONCLUSION: It could be concluded that LDL level can be considered as a risk factor for both ischemic and hemorrhagic cerebral events.

A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease.

RATIONALE: There is increasing evidence to suggest the possible efficacy of Crocus sativus (saffron) in the management of Alzheimer's disease (AD). OBJECTIVE: The purpose of the present investigation was to assess the efficacy of C. sativus in the treatment of patients with mild-to-moderate AD. METHODS: Fifty-four Persian-speaking adults 55 years of age or older who were living in the community were eligible to participate in a 22-week, double-blind study of parallel groups of patients with AD. The main efficacy measures were the change in the Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Dementia Rating Scale-Sums of Boxes scores compared with baseline. Adverse events (AEs) were systematically recorded. Participants were randomly assigned to receive a capsule saffron 30 mg/day (15 mg twice per day) or donepezil 10 mg/day (5 mg twice per day). RESULTS: Saffron at this dose was found to be effective similar to donepezil in the treatment of mild-to-moderate AD after 22 weeks. The frequency of AEs was similar between saffron extract and donepezil groups with the exception of vomiting, which occurred significantly more frequently in the donepezil group. CONCLUSION: This phase II study provides preliminary evidence of a possible therapeutic effect of saffron extract in the treatment of patients with mild-to-moderate Alzheimer's disease. This trial is registered with the Iranian Clinical Trials Registry (IRCT138711051556N1).

Cinnarizine in refractory migraine prophylaxis: efficacy and tolerability. A comparison with sodium valproate.

This was a double-blind clinical trial designed to assess the efficacy and safety of the cinnarizine (CIN) in patients with migraine who were refractory to propranolol and tricyclic antidepressants in comparison with sodium valproate (SV) to investigate whether CIN could be at least as effective as SV. A total of 125 patients were treated in a treatment period of 12 weeks. All patients had at least one intake of trial medication and 2-week post baseline efficacy observation which all were included in the ITT analysis. Of the 125 subjects treated, 46 discontinued prematurely: 25 from the CIN and 21 from the SV group. The main reasons for premature discontinuation were: lost to follow up (25/46, 63.2%), insufficient response (16/46, 20%), and adverse events (5/46, 12.8%). No statistically significant inter-group differences in the number of discontinuation was observed (p > 0.05). In both groups, number of attacks, intensity, and duration of attacks significantly decreased (p < 0.05). No statistically significant inter-group differences were observed regarding the mean number of attacks, duration, and intensity of migraine attacks for any of the time intervals analysed, except for the mean reduction of third and fourth visits intensity from baseline which were significantly different in two groups (p < 0.05), with the CIN group showing more reduction. Analysis of the number of responders showed that in the CIN group 61.2% subjects were responders, and 63.8% in the SV group. No statistically significant differences between the treatment groups were found for any of the secondary parameters. Overall 26 subjects reported one or more adverse events during the study period: 13 subjects in each group. Five subjects discontinued prematurely due to adverse events; two in the CIN group with significant weight gain, and 3 in the SV group with significant weight gain and severe tremor. These results suggest that CIN is an effective and safe prophylactic agent even in severe migraine headache.

Allopurinol as adjunctive therapy in intractable epilepsy: a double-blind and placebo-controlled trial.

BACKGROUND: Adenosine has been proposed to be an endogenous anticonvulsant agent. It inhibits glutamate release from excitatory neurons and neuronal firing. Therefore, adenosine agonists have potential clinical application as antiepileptics. In this double-blind randomized, placebo-controlled trial, we assessed the antiepileptic effect of allopurinol as an adjuvant agent in 38 patients with refractory epilepsy. METHODS: Thirty eight patients were randomly allocated equally to allopurinol+preexisting antiepileptic (Group A) or placebo+preexisting antiepileptic (Group B) for a 6-month, double-blind, placebo-controlled study. The dose of allopurinol was titrated up to 300 mg/day (100 mg TDS). The dose of preexisting medications was maintained without change over the trial. The effect of allopurinol was evaluated by a reduction in the total number of seizures per month and duration of seizure attacks. RESULTS: Of 38 participants, 32 patients completed the study. There were significant differences between the two groups in terms of reduction in the total number of seizure over the trial. Seizures reduction of >30% in 66%, >50% in 55%, and >60% in 44% of cases in the allopurinol group was achieved after 2 months and persisted during the study. Nevertheless, only during month 4 was there a significant difference between the two groups regarding reduction in seizure duration. In the allopurinol group, two patients had transient rashes, two patients had mild nausea, and two experienced dizziness, but only one patient discontinued the drug due to dizziness. In the placebo group, one patient had rash and one patient had nausea. In addition, no significant hematological or hepatic changes were found during the trial in both groups. CONCLUSIONS: The results suggest allopurinol as a safe and effective adjuvant agent in refractory epilepsy. Based on this study, we suggest that purine metabolism pathways and the specific use of allopurinol should be further investigated with regards to neurobiology and treatment of refractory epilepsy.