Polyvinylidene Fluoride Alters Inflammatory Responses by Activation-induced Cell Death in Macrophages

Carbon nanotubes (CNTs) are nanomaterials that have been employed in generating diverse materials. We previously reported that CNTs induce cell death in macrophages, possibly via asbestosis. Therefore, we generated CNT-attached polyvinylidene fluoride (PVDF), which is an established polymer in membrane technology, and then examined whether CNT-attached PVDF is immunologically safe for medical purposes compared to CNT alone. To test this, we treated RAW 264.7 murine macrophages (RAW cells) with CNT-attached PVDF and analyzed the production of nitric oxide (NO), a potent proinflammatory mediator, in these cells. RAW cells treated with CNT-attached PVDF showed reduced NO production in response to lipopolysaccharide. However, the same treatment also decreased the cell number suggesting that this treatment can alter the homeostasis of RAW cells. Although cell cycle of RAW cells was increased by PVDF treatment with or without CNTs, apoptosis was enhanced in these cells. Taken together, these results indicate that PVDF with or without CNTs modulates inflammatory responses possibly due to activation-induced cell death in macrophages.

Effects of Ascorbic and Dehydroascorbic Acids on Apoptotic Cell Death in Hippocampal Slice Culture

Ascorbic acid (AA) and dehydroascorbic acid (DHA) are known to have protective effects in experimental central nerve system disorder models such as stroke, ischemia, and epileptic seizures. The present study was conducted to examine the protective effect of AA and DHA on kainic acid (KA) neurotoxicity using organotypic hippocampal slice cultures (OHSC). Protective effects of AA and DHA on KA-induced cell death were evaluated by analyzing caspase-3. In addition, to determine if the prooxidant effect of AA is related to iron, the effect of AA on cell death was examined using desferrioxamine (DFO), an iron chelator. After 12h-KA treatment, significant delayed neuronal death was detected in CA3 region, but not in CA1. The AA (500 micrometer) and DHA (100 and 500 micrometer) pretreatments significantly prevented cell death by inhibiting caspase-3 activation in CA3 region. In the concentration of 1,000 micrometer, however, AA pretreatment might have prooxidant effect, but AA-induced oxidative reaction is mainly not related to transition metal ions. These data showed that the pretreatments of intermediate-dose AA and DHA protected KA-induced neuronal damage in OHSCs and co-pretreatment of AA and DFO did not affect cell death except for a few cases. These data suggest that both AA and DHA pretreatment have antioxidant or prooxidant effect depending on doses treated on KA-induced neuronal injury and the possible prooxidant effect of AA may not depend on the Fenton reaction.

Behavioral Characteristics of a Mouse Model of Cancer Pain

Pain is a major symptom in cancer patients, and most cancer patients with advanced or terminal cancers suffer from chronic pain related to treatment failure and/or tumor progression. In the present study, we examined the development of cancer pain in mice. Murine hepatocarcinoma cells, HCa-1, were inoculated unilaterally into the thigh or the dorsum of the foot of male C3H/HeJ mice. Four weeks after inoculation, behavioral signs were observed for mechanical allodynia, cold allodynia, and hyperalgesia using a von Frey filament, acetone, and radiant heat, respectively. Bone invasion by the tumor commenced from 7 days after inoculation of tumor cells and was evident from 14 days after inoculation. Cold allodynia but neither mechanical allodynia nor hyperalgesia was observed in mice that received an inoculation into the thigh. On the contrary, mechanical allodynia and cold allodynia, but not hyperalgesia, were developed in mice with an inoculation into the foot. Sometimes, mirror-image pain was developed in these animals. These results suggest that carcinoma cells injected into the foot of mice may develop severe chronic pain related to cancer. This animal model of pain would be useful to elucidate the mechanisms of cancer pain in humans.

Role of different peripheral components in the expression of neuropathic pain syndrome

Peripheral nerve injury frequently leads to neuropathic pain like hyperalgesia, spontaneous pain, mechanical allodynia, thermal allodynia. It is uncertain where the neuropathic pain originates and how it is transmitted to the central nervous system. This study was performed in order to determine which peripheral component may lead to the symptoms of neuropathic pain. Under halothane anesthesia, male Sprague-Dawley rats were subjected to neuropathic surgery by tightly ligating and cutting the tibial and sural nerves and leaving the common peroneal nerve intact. Behavioral tests for mechanical allodynia, thermal allodynia, and spontaneous pain were performed for 2 weeks postoperatively. Subsequently, second operation was performed as follows: in experiment 1, the neuroma was removed; in experiment 2, the dorsal roots of the L4-L6 spinal segments were cut; in experiment 3, the dorsal roots of the L2-L6 spinal segments were cut. Behavioral tests were performed for 4 weeks after the second operation. Following the removal of the neuroma, neuropathic pain remained in experiment 1. After the cutting of the L4-L6 or L2-L6 dorsal roots, neuropathic pain was reduced in experiments 2 and 3. The most remarkable relief was seen after the cutting of the L2-L6 dorsal roots in experiment 3. According to the fact that the sciatic nerve is composed of the L4-L6 spinal nerves and the femoral nerve is composed of the L2-L4 spinal nerves, neuropathic pain is transmitted to the central nervous system via not only the injured nerves but also adjacent intact nerves. These results also suggest that the dorsal root ganglion is very important in the development of neuropathic pain syndrome.

An analysis of the family medicine education of second-grade medical students

No abstract available.