Effects of vitamin treatment or supplements with purported antioxidant properties on skin cancer prevention: a meta-analysis of randomized controlled trials.

AIMS: To investigate the effect of vitamin treatment or supplements with purported antioxidant properties on the primary and secondary prevention of skin cancer using a meta-analysis of randomized controlled trials (RCTs). METHODS: We searched PubMed, Embase and the Cochrane Library in June 2009. Among 398 articles searched, 11 articles on 10 RCTs were included in the final analysis. RESULTS: In a fixed-effects meta-analysis of all 10 trials, vitamin treatment or supplements with purported antioxidant properties were found to have no preventive effect on skin cancer [relative risk (RR) = 0.98; 95% confidence interval (CI) = 0.94-1.03]. Similar findings were observed in a subgroup meta-analysis of 10 studies on both primary prevention trials (RR = 0.98; 95% CI = 0.93-1.03) and secondary prevention trials (RR = 0.97; 95% CI = 0.83-1.13). Further, subgroup meta-analyses revealed no preventive effect on cancer by type of antioxidant, type of cancer and the methodological quality of the studies. CONCLUSION: The current meta-analysis of RCTs indicated that there is no clinical evidence to support an overall primary and secondary preventive effect of vitamin treatment or supplements with purported antioxidant properties on skin cancer. The effect of vitamin supplements on skin cancer should not be overemphasized.

[The proportional mortality ratios of specific-cause mortality by occupation and education among men aged 20-64 in Korea (1993-2004)].

OBJECTIVES: This study investigated the relationship of occupational class and educational background with proportional mortality ratios in Korea. METHODS: Mortality was investigated using the entire registered death data from 1993 to 2004, obtained from the Korean National Statistics Office. Proportional mortality ratios (PMRs) for specific diseases were calculated according to the occupational class and educational background of men aged 20-64. RESULTS: Manual workers were found to have higher PMRs for liver disease and traffic accidents, as did the lower educated group. Especially, this study showed trends of an increasing of the wide gap between lower and higher socioeconomic stati for liver disease, traffic accidents, diabetes mellitus and cerebral vascular disease. The mortality for cerebrovascular disease, diabetes mellitus, heart disease, traffic accident and liver disease showed increasing trends according to the calendar year for the lower than the higher social class. CONCLUSIONS: The specific conditions that had higher PMRs in the Korean lower social class were liver disease and traffic accidents. Especially, there was an increasing trend for a widening of the gap between manual and non-manual groups in relation to mortality from liver disease, diabetes mellitus and traffic accidents.

Lack of reciprocity between opioid and 5-HT3 receptors for antinociception in rat spinal cord.

We examined the properties of the drug interaction between morphine and 5-HT(3) receptor antagonist at the spinal level. The nociceptive state was induced by subcutaneously injecting formalin solution (5%, 50 microl) into the hindpaw of the rats. Intrathecal morphine and m-CPBG (5-HT(3) receptor agonist) dose-dependently decreased the flinching response during phase 1 and phase 2 in the formalin test. Intrathecal 5-HT(3) receptor antagonists (LY-278,584 and ondansetron) did not reverse the antinociceptive effect of intrathecal morphine. Intrathecal naloxone had little effect on attenuation of the antinociception of intrathecal m-CPBG. Taken together, no reciprocal interaction was noted between 5-HT(3) receptor and opioid receptors at the spinal level. Thus, the 5-HT(3) receptor antagonist may be useful to manage opioid-induced emesis at the spinal level.

Roles of adenosine receptor subtypes in the antinociceptive effect of intrathecal adenosine in a rat formalin test.

The contributions of adenosine receptor subtypes to antinociception produced by adenosine were determined at the spinal level. There are 4 types of adenosine receptors, namely A1, A(2A), A(2B) and A3. The authors investigated the properties of the subtypes of spinal adenosine receptors in terms of nociceptive modulation. The nociceptive state was induced by subcutaneously injecting formalin solution (5%, 50 microl) into the hind paws of male Sprague-Dawley rats. After observing the effect of intrathecal adenosine during the formalin test, the effects of intrathecal adenosine A1 (CPT), A(2A) (CSC), A(2B) (alloxazine) and A3 (MRS 1220) receptor antagonists on the action of adenosine were examined. Intrathecal adenosine inhibited phase 2 flinching response without affecting phase 1 response. CPT, CSC, alloxazine and MRS 1220 antagonized the antinociceptive action of adenosine during phase 2 of the formalin test. These results suggest that spinal adenosine A1, A(2A), A(2B) and A3 receptors may play an important role in the antinociception of adenosine in the formalin-induced facilitated state.

Antinociceptive effects and synergistic interaction with morphine of intrathecal metabotropic glutamate receptor 2/3 antagonist in the formalin test of rats.

Spinal metabotropic glutamate receptors (mGluRs) have been known to be involved in the modulation of nociception. While the antinociceptive effects of the mGluR1/5 have been demonstrated, the role of mGluR2/3 for nociception is less clear. This study investigated the effects of an intrathecal mGluR2/3 agonist, APDC, and a mGluR2/3 antagonist, LY341495, for inflammatory and acute pain in the formalin test and thermal stimulation test. We also examined their interaction with intrathecal morphine for the antinociceptive effect. APDC had little effect on the formalin-induced nociception. In contrast, LY341495 caused a dose-dependent suppression of the phase 2 flinching response to the formalin stimulus without affecting phase 1 flinching response. Furthermore, the suppression of pain behavior by LY341495 during phase 2 was reduced significantly by pretreatment with APDC. LY341495 and morphine also showed synergistic drug interaction for antinociception during phase 2 in the formalin test.

Evaluation of interaction between intrathecal adenosine and MK801 or NBQX in a rat formalin pain model.

Adenosine and excitatory amino acids have been known to be involved in modulating nociceptive transmission at the spinal level. The authors assessed the characteristics of the interaction of the adenosine-excitatory amino acid antagonist combinations in the spinal cord of rats on the formalin-induced nociception. Intrathecal NMDA antagonist ((5R, 10S)-(+)-5-methyl-10,11-dihydro-(5)H-dibenzo[a[,]d]cyclohepten-5,10-imine hydrogen maleate, MK801, 30 microg) and AMPA antagonist (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[F]quinoxaline-7-sulfonamide, NBQX, 3 microg) decreased the total number of flinches during both phases in the formalin test. Intrathecal adenosine (300 microg) had little effect on the phase 1 flinching response, but decreased the phase 2 response. The fixed dose analysis and the isobolographic analysis revealed that adenosine interacts additively with MK801 and NBQX in the spinal cord.

Lack of the nitric oxide-cyclic GMP-potassium channel pathway for the antinociceptive effect of intrathecal zaprinast in a rat formalin test.

Zaprinast is a phosphodiesterase inhibitor that is active in various models of pain when administered locally. In addition, the antinociception of zaprinast is involved in the nitric oxide (NO)-cGMP pathway. However, the effect of zaprinast administered spinally has not been examined. Therefore, this study examined the effect of zaprinast on the formalin-induced nociception at the spinal level. Next, the role of the NO-cGMP-potassium channel pathway on the effect of zaprinast was further clarified. Catheters were inserted into the intrathecal space of male Sprague-Dawley (SD) rats. Pain was induced by applying 50 microl of a 5% formalin solution to the hindpaw. The change in the zaprinast-induced effect was examined after an intrathecal pretreatment with a NO synthase inhibitor (l-NMMA), a guanylyl cyclase inhibitor (ODQ) or a potassium channel blocker (glibenclamide). Zaprinast produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Intrathecal l-NMMA, ODQ and glibenclamide did not reverse the antinociception of zaprinast in either phase of the formalin test. These results suggest that zaprinast is effective against both acute pain and the facilitated pain state at the spinal level. However, the NO-sensitive cGMP-potassium channel pathway is not contributable to the antinociceptive mechanism of zaprinast in the spinal cord.