RhoA affects oral morphine analgesia depending on functional variation in intestinal P-glycoprotein induced by repeated etoposide treatment.

In early palliative care, drug-drug interactions between opioids and anticancer agents may be caused by combined treatment with these drugs. We previously reported that repeated administration of oral etoposide (ETP), an anticancer drug that is a substrate of P-glycoprotein (P-gp), caused attenuation of the analgesic effect of oral morphine through up-regulation of intestinal P-gp. Recent studies have revealed that RhoA, a small G-protein, is involved in the regulation of P-gp expression and activity.

Involvement of ubiquitination in the decrease of intestinal P-glycoprotein in a streptozotocin-induced diabetic mouse model.

P-Glycoprotein (P-gp), one of the drug efflux pumps, is expressed in some tissues and may affect the pharmacokinetics of its substrates. We have previously reported that a decrease of intestinal P-gp expression affects the pharmacokinetics of orally-administered P-gp substrate drugs in a streptozotocin (STZ)-induced type 1 diabetic mice model. Although we have found the participation of nitric oxide synthase (NOS) activation as a mechanism of the decrease in intestinal P-gp expression under diabetic conditions, more detailed mechanisms other than NOS remain unknown.

The involvement of cleavage of neural cell adhesion molecule in neuronal death under oxidative stress conditions in cultured cortical neurons.

Neural cell adhesion molecule (NCAM) is a member of the immunoglobulin superfamily with an important function in the central nervous system, particularly in synapse stabilization and neurite outgrowth. Our recent study clearly demonstrated that cleavage of NCAM-180 by matrix metalloproteinase-9 (MMP-9) exacerbated the neuronal damage induced by in vivo ischemic stress. In the present study, we investigated the effect of oxidative stress on the expression levels of full-length NCAM-180 and NCAM-cleavage product (65 kDa) and the relationship between NCAM-180 and MMP-9 in cultured cortical neurons.

Involvement of matrix metalloproteinase-9 in the development of morphine tolerance.

Matrix metalloproteinase-9 (MMP-9) is involved in tissue remodeling or neural plasticity in various clinical states (e.g. inflammation, neuropathic pain).

Etoposide modulates the effects of oral morphine analgesia by targeting the intestinal P-glycoprotein.

Objectives: Opioids and anticancer compounds such as etoposide (ETP) are substrates of P-glycoprotein (P-gp), an ATP-dependent efflux pump. Chemotherapy compounds may impact on the analgesic effect of opioids such as morphine when the two drugs are co-administered. In this study, we used a mouse model to determine if there is a pharmacological interaction between ETP and morphine, focusing on the involvement of intestinal P-gp.

[Altered intestinal P-glycoprotein expression levels affect pharmacodynamics under diabetic condition].

P-glycoprotein (P-gp), one of the important drug-efflux pumps, is known to affect pharmacokinetics and pharmacodynamics of P-gp substrate drugs. We have previously reported that intestinal P-gp expression levels are transiently decreased in streptozotocin (STZ)-induced type 1 diabetic mouse model. Herein, we examined the analgesic effects of orally administered morphine and its pharmacokinetic properties under diabetic conditions, specifically focusing on the involvement of intestinal P-gp in a type 1 diabetic mouse model.

Honokiol suppresses the development of post-ischemic glucose intolerance and neuronal damage in mice.

Honokiol, a constituent of Magnolia obovata, has various pharmacological effects, including protection against cerebral ischemia. However, few studies have been conducted to evaluate the possible neuroprotective effects of honokiol against cerebral ischemia. We recently reported that cerebral ischemic neuronal damage could be triggered by glucose intolerance that develops after the onset of ischemic stress (i.

RETRACTED: Ameliorating Effect of Hypothalamic Brain-Derived Neurotrophic Factor Against Impaired Glucose Metabolism After Cerebral Ischemic Stress in Mice.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).

Ischemic Stroke and Glucose Intolerance: a Review of the Evidence and Exploration of Novel Therapeutic Targets.

Stroke is one of the leading causes of death and disability worldwide. It is well known that hyperglycemia and/or diabetes potentially exacerbate the neuronal damage observed following ischemic stroke. Recent reports have shown that hyperglycemia/glucose intolerance may be induced by cerebral ischemic stress, and that normalization of blood glucose levels during the first 48 h of hospitalization appears to confer greater survival outcomes in stroke patients.

Ameliorating effect of hypothalamic brain-derived neurotrophic factor against impaired glucose metabolism after cerebral ischemic stress in mice.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has potent neuroprotective effects against brain injury. We recently reported that glucose intolerance/hyperglycemia could be induced by ischemic stress (i.e.

Ischemic stroke and glucose intolerance: a review of the evidence and exploration of novel therapeutic targets.

Stroke is one of the leading causes of death and disability worldwide. It is well known that hyperglycemia and/or diabetes potentially exacerbate the neuronal damage observed following ischemic stroke. Recent reports have shown that hyperglycemia/glucose intolerance may be induced by cerebral ischemic stress, and that normalization of blood glucose levels during the first 48 h of hospitalization appears to confer greater survival outcomes in stroke patients.

Altered intestinal P-glycoprotein expression levels in a monosodium glutamate-induced obese mouse model.

Aims: P-glycoprotein (P-gp) is an important drug efflux transporter located in many tissues such as the blood-brain barrier, intestines, liver and kidneys. We have previously reported that ileal P-gp expression levels decrease via a nitric oxide synthase (NOS)-mediated pathway in a streptozotocin (STZ)-induced type 1 diabetic mouse model. Herein, our objective was to assess whether there are differences in the expression of intestinal P-gp in an obesity-induced hyperglycemic mouse model versus the type 1 diabetic mouse model.

Decreased expression of intestinal P-glycoprotein increases the analgesic effects of oral morphine in a streptozotocin-induced diabetic mouse model.

Morphine is one of the strongest analgesics and is commonly used for the treatment of chronic pain. The pharmacokinetic properties of morphine are, in part, modulated by P-glycoprotein (P-gp). We previously reported that intestinal P-gp expression levels are influenced via the activation of inducible nitric oxide synthase (iNOS) in streptozotocin (STZ)-induced diabetic mice.

Aβ and Aδ but not C-fibres are involved in stroke related pain and allodynia: an experimental study in mice.

Objectives: Cerebral ischaemia is a leading cause of death and disability, including severe complications such as memory disturbance, palsy, and spasticity. Central post-stroke pain (CPSP) is a complication of cerebral ischaemia, and is characterized clinically by spontaneous pain and attacks of allodynia and dysaesthesia. However, the detailed mechanisms of CPSP are not well established.

Involvement of matrix metalloproteinase-mediated proteolysis of neural cell adhesion molecule in the development of cerebral ischemic neuronal damage.

Neural cell adhesion molecule (NCAM) is a membrane protein abundantly expressed in the central nervous system. Recently, it has been reported that dysfunction of NCAM is linked to human brain disorders. Furthermore, NCAM is one of the proteolysis targets of matrix metalloproteinase (MMP), whose activation is implicated in neuronal damage.

Involvement of NCAM and FGF receptor signaling in the development of analgesic tolerance to morphine.

This study examined the involvement of neural cell adhesion molecule (NCAM), a member of the immunoglobulin superfamily, in the development of tolerance to morphine. Furthermore, we focused on fibroblast growth factor (FGF) receptor and protein kinase C (PKC)-α as part of the intracellular signal transduction pathways underlying NCAM stimulation. The development of analgesic tolerance to morphine was gradually observed during daily treatment of morphine (10mg/kg, s.

[Effectiveness of metformin in prevention of development of hyperglycemia and neuronal damage caused by ischemic stress].

Hyperglycemia is a known exacerbating factor in ischemic stroke. It has been reported that hyperglycemia and post-ischemic glucose intolerance can develop after stroke and be involved in the development of neuronal damage, as we described previously. Here, we focus on the effectiveness of metformin, a hypoglycemic drug, in preventing the development of neuronal damage using the middle cerebral artery occlusion (MCAO) model mice.

[Nitric oxide synthase-mediated alteration of intestinal P-glycoprotein under hyperglycemic stress].

P-glycoprotein (P-gp), one of the important drug-efflux pumps, is known to be affected by pathological conditions such as inflammation or infection. Recently, it is reported that high glucose or hyperglycemia can alter P-gp expression levels at the blood-brain barrier or in kidney, although the details are still unknown. Here, we analyzed the alteration of intestinal P-gp expression and function in the development of diabetes and elucidated the mechanisms.

Regulatory action of nitric oxide synthase on ileal P-glycoprotein expression under streptozotocin-induced diabetic condition.

P-glycoprotein (P-gp), a drug efflux transporter, affects the pharmacokinetics of a wide range of substrate drugs. Our previous study clearly revealed that intestinal P-gp expression levels were decreased via an inducible nitric oxide synthase (iNOS)-mediated mechanism in the early phases of diabetes. Here, we focused on changes in ileal P-gp expression and the influences of NOS on the P-gp expression levels in the later phase of diabetic condition using streptozotocin (STZ)-induced diabetic mice.

Effect of orexin-A on post-ischemic glucose intolerance and neuronal damage.

Orexin-A is a newly identified neuropeptide expressed in the lateral areas of the hypothalamus that plays a role in various physiological functions, including regulation of glucose metabolism. We have previously reported that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage. Therefore, the aim of this study was to determine the effects of orexin-A on the development of post-ischemic glucose intolerance and ischemic neuronal damage.

The antinociceptive and anti-inflammatory action of the CHCl3-soluble phase and its main active component, damnacanthal, isolated from the root of Morinda citrifolia.

Morinda citrifolia (Rubiaceae, Noni) is a traditional medicine with various pharmacological activities. We investigated if the MeOH-, CHCl(3)- and BuOH-soluble phase and its main active component, damnacanthal, isolated from the Noni root, have antinociceptive and anti-inflammatory actions in mice. The CHCl(3)-soluble phase (3 g/kg, per os (p.

RETRACTED: Effect of Orexin-A on Post-ischemic Glucose Intolerance and Neuronal Damage.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).

Involvement of kappa opioid receptors in the formalin-induced inhibition of analgesic tolerance to morphine via suppression of conventional protein kinase C activation.

Objectives: Repeated morphine treatment results in a decreased analgesic effect or the development of analgesic tolerance. However, we reported that some inflammatory chronic pain may inhibit morphine tolerance via kappa opioid receptor (KOR) activation. In this study, we further investigated the role of KOR in the inhibition of morphine tolerance in a chronic pain condition with a focus on the regulation of protein kinase C (PKC) activity.