European Journal of Pharmaceutical Sciences, Feb 12, 2015
Appropriate therapeutics for wound treatments can be achieved by studying the pathophysiology of ... more Appropriate therapeutics for wound treatments can be achieved by studying the pathophysiology of tissue
repair. Here we develop formulations of lamellar gel phase (LGP) emulsions containing marigold
(Calendula officinalis) oil, evaluating their stability and activity on experimental wound healing in rats.
LGP emulsions were developed and evaluated based on a phase ternary diagram to select the best LGP
emulsion, having a good amount of anisotropic structure and stability. The selected LGP formulation
was analyzed according to the intrinsic and accelerated physical stability at different temperatures. In
addition, in vitro and in vivo studies were carried out on wound healing rats as a model. The LGP emulsion
(15.0% marigold oil; 10.0% of blend surfactants and 75.0% of purified water [w/w/w]) demonstrated good
stability and high viscosity, suggesting longer contact of the formulation with the wound. No cytotoxic
activity (50–1000 lg/mL) was observed in marigold oil. In the wound healing rat model, the LGP
(15 mg/mL) showed an increase in the leukocyte recruitment to the wound at least on days 2 and 7,
but reduced leukocyte recruitment after 14 and 21 days, as compared to the control. Additionally, collagen
production was reduced in the LGP emulsion on days 2 and 7 and further accelerated the process of
re-epithelialization of the wound itself. The methodology utilized in the present study has produced a
potentially useful formulation for a stable LGP emulsion-containing marigold, which was able to improve
the wound healing process.
Idiopathic osteonecrosis of the femoral head (ION) is a devastating pathological condition of unk... more Idiopathic osteonecrosis of the femoral head (ION) is a devastating pathological condition of unknown etiology. In this study, we developed a simple murine model of osteonecrosis and investigated the underlying molecular mechanisms. In this model, the central portion of the tails of male C57BL/6 mice were tightly ligated to produce ischemic regions at sites distal to the ligatures. The occlusive ligatures were maintained for the indicated periods and then removed to induce reperfusion. The tails were histologically examined, and gene expression was analyzed by PCR array. The effect of p53 expression on osteocytes apoptosis was examined using preosteocytic MLO-A5 cells. In addition, the expression of p53 was analyzed in the femoral head samples obtained from hip osteoarthritis (OA) patients and ION patients. Caudal vertebrae distal to the ligatures (distal region) exhibited histological changes mimicking those observed in ION. Expression of p53 was increased in the distal region, and overexpression of p53 induced apoptosis in MLO-A5 cells. Treatment with a p53 inhibitor suppressed osteocyte apoptosis in the distal region. Strong p53 immunostaining was observed in osteocytes, vascular endothelial cells, and bone marrow cells in the femoral heads from ION patients but not from OA patients. Ischemia/reperfusion of the caudal vertebrae is a useful murine model of osteonecrosis, mimicking the histological changes found in ION. Using this model, we found the possible involvement of p53 in the osteocyte apoptosis observed in ION. Therapeutics targeting p53 might be a useful approach to ameliorating or even preventing osteonecrosis in ION patients.
European Journal of Pharmaceutical Sciences, Feb 12, 2015
Appropriate therapeutics for wound treatments can be achieved by studying the pathophysiology of ... more Appropriate therapeutics for wound treatments can be achieved by studying the pathophysiology of tissue
repair. Here we develop formulations of lamellar gel phase (LGP) emulsions containing marigold
(Calendula officinalis) oil, evaluating their stability and activity on experimental wound healing in rats.
LGP emulsions were developed and evaluated based on a phase ternary diagram to select the best LGP
emulsion, having a good amount of anisotropic structure and stability. The selected LGP formulation
was analyzed according to the intrinsic and accelerated physical stability at different temperatures. In
addition, in vitro and in vivo studies were carried out on wound healing rats as a model. The LGP emulsion
(15.0% marigold oil; 10.0% of blend surfactants and 75.0% of purified water [w/w/w]) demonstrated good
stability and high viscosity, suggesting longer contact of the formulation with the wound. No cytotoxic
activity (50–1000 lg/mL) was observed in marigold oil. In the wound healing rat model, the LGP
(15 mg/mL) showed an increase in the leukocyte recruitment to the wound at least on days 2 and 7,
but reduced leukocyte recruitment after 14 and 21 days, as compared to the control. Additionally, collagen
production was reduced in the LGP emulsion on days 2 and 7 and further accelerated the process of
re-epithelialization of the wound itself. The methodology utilized in the present study has produced a
potentially useful formulation for a stable LGP emulsion-containing marigold, which was able to improve
the wound healing process.
Idiopathic osteonecrosis of the femoral head (ION) is a devastating pathological condition of unk... more Idiopathic osteonecrosis of the femoral head (ION) is a devastating pathological condition of unknown etiology. In this study, we developed a simple murine model of osteonecrosis and investigated the underlying molecular mechanisms. In this model, the central portion of the tails of male C57BL/6 mice were tightly ligated to produce ischemic regions at sites distal to the ligatures. The occlusive ligatures were maintained for the indicated periods and then removed to induce reperfusion. The tails were histologically examined, and gene expression was analyzed by PCR array. The effect of p53 expression on osteocytes apoptosis was examined using preosteocytic MLO-A5 cells. In addition, the expression of p53 was analyzed in the femoral head samples obtained from hip osteoarthritis (OA) patients and ION patients. Caudal vertebrae distal to the ligatures (distal region) exhibited histological changes mimicking those observed in ION. Expression of p53 was increased in the distal region, and overexpression of p53 induced apoptosis in MLO-A5 cells. Treatment with a p53 inhibitor suppressed osteocyte apoptosis in the distal region. Strong p53 immunostaining was observed in osteocytes, vascular endothelial cells, and bone marrow cells in the femoral heads from ION patients but not from OA patients. Ischemia/reperfusion of the caudal vertebrae is a useful murine model of osteonecrosis, mimicking the histological changes found in ION. Using this model, we found the possible involvement of p53 in the osteocyte apoptosis observed in ION. Therapeutics targeting p53 might be a useful approach to ameliorating or even preventing osteonecrosis in ION patients.
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Papers by C Okuma
repair. Here we develop formulations of lamellar gel phase (LGP) emulsions containing marigold
(Calendula officinalis) oil, evaluating their stability and activity on experimental wound healing in rats.
LGP emulsions were developed and evaluated based on a phase ternary diagram to select the best LGP
emulsion, having a good amount of anisotropic structure and stability. The selected LGP formulation
was analyzed according to the intrinsic and accelerated physical stability at different temperatures. In
addition, in vitro and in vivo studies were carried out on wound healing rats as a model. The LGP emulsion
(15.0% marigold oil; 10.0% of blend surfactants and 75.0% of purified water [w/w/w]) demonstrated good
stability and high viscosity, suggesting longer contact of the formulation with the wound. No cytotoxic
activity (50–1000 lg/mL) was observed in marigold oil. In the wound healing rat model, the LGP
(15 mg/mL) showed an increase in the leukocyte recruitment to the wound at least on days 2 and 7,
but reduced leukocyte recruitment after 14 and 21 days, as compared to the control. Additionally, collagen
production was reduced in the LGP emulsion on days 2 and 7 and further accelerated the process of
re-epithelialization of the wound itself. The methodology utilized in the present study has produced a
potentially useful formulation for a stable LGP emulsion-containing marigold, which was able to improve
the wound healing process.
repair. Here we develop formulations of lamellar gel phase (LGP) emulsions containing marigold
(Calendula officinalis) oil, evaluating their stability and activity on experimental wound healing in rats.
LGP emulsions were developed and evaluated based on a phase ternary diagram to select the best LGP
emulsion, having a good amount of anisotropic structure and stability. The selected LGP formulation
was analyzed according to the intrinsic and accelerated physical stability at different temperatures. In
addition, in vitro and in vivo studies were carried out on wound healing rats as a model. The LGP emulsion
(15.0% marigold oil; 10.0% of blend surfactants and 75.0% of purified water [w/w/w]) demonstrated good
stability and high viscosity, suggesting longer contact of the formulation with the wound. No cytotoxic
activity (50–1000 lg/mL) was observed in marigold oil. In the wound healing rat model, the LGP
(15 mg/mL) showed an increase in the leukocyte recruitment to the wound at least on days 2 and 7,
but reduced leukocyte recruitment after 14 and 21 days, as compared to the control. Additionally, collagen
production was reduced in the LGP emulsion on days 2 and 7 and further accelerated the process of
re-epithelialization of the wound itself. The methodology utilized in the present study has produced a
potentially useful formulation for a stable LGP emulsion-containing marigold, which was able to improve
the wound healing process.