Ahmed Maher - Academia.edu (original) (raw)

Papers by Ahmed Maher

Research paper thumbnail of Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks

Drug Delivery, 2021

Abstract Ciclesonide (CIC), an inhaled corticosteroid for bronchial asthma is currently available... more Abstract Ciclesonide (CIC), an inhaled corticosteroid for bronchial asthma is currently available as metered dose inhaler (CIC–MDI) which possesses a major challenge in the management of the elderly, critically ill patients and children. In this work, nebulized CIC nano-structure lipid particles (CIC-NLPs) were prepared and evaluated for their deep pulmonary delivery and cytotoxicity to provide additional clinical benefits to patients in controlled manner and lower dose. The bio-efficacy following nebulization in ovalbumin (OVA) induced asthma Balb/c mice compared to commercial (CIC–MDI) was also assessed. The developed NLPs of 222.6 nm successfully entrapped CIC (entrapment efficiency 93.3%) and exhibited favorable aerosolization efficiency (mass median aerodynamic diameter (MMAD) 2.03 μm and fine particle fraction (FPF) of 84.51%) at lower impactor stages indicating deep lung deposition without imparting any cytotoxic effect up to a concentration of 100 μg/ml. The nebulization of 40 µg dose of the developed CIC-NLPs revealed significant therapeutic impact in the mitigation of the allergic airways inflammations when compared to 80 µg dose of the commercial CIC–MDI inhaler (Alvesco®). Superior anti-inflammatory and antioxidative stress effects characterized by significant decrease (p< .0001) in inflammatory cytokines IL-4 and 13, serum IgE levels, malondialdehyde (MDA), nitric oxide (NO), TNF-α, and activated nuclear factor-κB (NF-κB) activity were obvious with concomitant increase in superoxide dismutase (SOD) activity. Histological examination with inhibition of inflammatory cell infiltration in the respiratory tract was correlated well with observed biochemical improvement.

Research paper thumbnail of The Role of Nitric Oxide from Neurological Disease to Cancer

Advances in experimental medicine and biology, 2017

Until the beginning of the 1980s, nitric oxide (NO) was just a toxic molecule of a lengthy list o... more Until the beginning of the 1980s, nitric oxide (NO) was just a toxic molecule of a lengthy list of environmental pollutants such as cigarette smoke and smog. In fact, NO had a very bad reputation of being destroyer of ozone, suspected carcinogen and precursor of acid rain. However, by the early 1990s it was well recognized by the medical research community. Over the last two decades, the picture has been totally changed. Diverse lines of evidence have converged to show that this sometime poison is a fundamental player in the everyday business of the human body. NO activity was probed in the brain, arteries, immune system, liver, pancreas, uterus, peripheral nerves, lungs, and almost every system in the human body. NO is a major player in the cardiovascular system as it is involved in regulating blood pressure. In the CNS, it is involved in memory formation and the regulation of cerebral blood flow to ensure adequate supply of blood to the brain. Because NO is involved in many pathwa...

Research paper thumbnail of The Role of Systemic Inflammation, Nitric Oxide Signaling, and NMDA Receptors in an Experimental Model of Alzheimer’s Disease

Alzheimer’s disease is (AD) a common form of age-related dementia, characterized by deposition of... more Alzheimer’s disease is (AD) a common form of age-related dementia, characterized by deposition of amyloid A plaques, neuroinflammation and neurodegeneration. Nitric oxide (NO) signaling has been involved in related neuronal processes: NO is involved in memory development and neuroinflammation, neuronal NO synthase (nNOS) is believed to contribute to memory formation, while inducible NO synthase (iNOS) mediates inflammatory processes in the CNS. Here, we study the contribution of LPS-induced systemic inflammation, as well as the role of NO signaling on incidence and progression of induced AD, and whether L-arginine can ameliorate AD-related dysfunctions. AD was induced in mice by a single dose of lipopolysaccharide (LPS). Behavioral tests for spatial and non-spatial memory and locomotor activity were performed to assess disease severity and progression. The effects of L-NAME (general NOS inhibitor), 1400W (iNOS inhibitor), Diflunisal (systemic anti-inflammatory drug that does not cr...

Research paper thumbnail of Detection of Pulmonary Embolism on CT-Angiography Using Contrast Attenuation of Pulmonary Veins

Acta Angiologica, 2021

Introduction: In areas of pulmonary embolism (PE), the enhancement of pulmonary veins on computed... more Introduction: In areas of pulmonary embolism (PE), the enhancement of pulmonary veins on computed tomography pulmonary angiography (CTPA) should be decreased due to reduced arterial perfusion. The purpose of this study was to investigate the accuracy of contrast density measurements (differences) in all pulmonary veins and the left atrium for the prediction of PE. Material and methods: Seventy-five patients with PE and 22 patients without PE on CTPA were included. Four readers measured the enhancement of the blood in the pulmonary vein immediately before the entrance to the left atrium, right after the aperture, in the center of the left atrium, in the pulmonary trunk and in the aorta. Enhancement of the pulmonary veins with and without upstream PE, and ROC curves with HU thresholds for optimal sensitivity and specificity for PE were calculated. Results: More PEs were found in the right and lower lobes. PE-affected lobes demonstrated 13.8 ± 45 HU less enhancement in the pulmonary vein, compared to a paired non-affected pulmonary vein of the same patient (P < 0.0001). On average, non-affected pulmonary veins demonstrated no difference in enhancement compared to each other: 0.2 ± 21 HU. The optimal cutoff level in the ROC curve analysis for PE affection proved to be decreasing enhancement in the pulmonary vein of more than 10 HU compared to the atrium. Conclusion: Decreasing enhancement in the pulmonary vein of more than 10 HU compared to the atrium could provide additional information and confidence in the diagnosis of PE.

Research paper thumbnail of Enhanced alveo pulmonary deposition of nebulized ciclesonide for attenuating airways inflammations: a strategy to overcome metered dose inhaler drawbacks

Drug Delivery, 2021

Abstract Ciclesonide (CIC), an inhaled corticosteroid for bronchial asthma is currently available... more Abstract Ciclesonide (CIC), an inhaled corticosteroid for bronchial asthma is currently available as metered dose inhaler (CIC–MDI) which possesses a major challenge in the management of the elderly, critically ill patients and children. In this work, nebulized CIC nano-structure lipid particles (CIC-NLPs) were prepared and evaluated for their deep pulmonary delivery and cytotoxicity to provide additional clinical benefits to patients in controlled manner and lower dose. The bio-efficacy following nebulization in ovalbumin (OVA) induced asthma Balb/c mice compared to commercial (CIC–MDI) was also assessed. The developed NLPs of 222.6 nm successfully entrapped CIC (entrapment efficiency 93.3%) and exhibited favorable aerosolization efficiency (mass median aerodynamic diameter (MMAD) 2.03 μm and fine particle fraction (FPF) of 84.51%) at lower impactor stages indicating deep lung deposition without imparting any cytotoxic effect up to a concentration of 100 μg/ml. The nebulization of 40 µg dose of the developed CIC-NLPs revealed significant therapeutic impact in the mitigation of the allergic airways inflammations when compared to 80 µg dose of the commercial CIC–MDI inhaler (Alvesco®). Superior anti-inflammatory and antioxidative stress effects characterized by significant decrease (p< .0001) in inflammatory cytokines IL-4 and 13, serum IgE levels, malondialdehyde (MDA), nitric oxide (NO), TNF-α, and activated nuclear factor-κB (NF-κB) activity were obvious with concomitant increase in superoxide dismutase (SOD) activity. Histological examination with inhibition of inflammatory cell infiltration in the respiratory tract was correlated well with observed biochemical improvement.

Research paper thumbnail of The Role of Nitric Oxide from Neurological Disease to Cancer

Advances in experimental medicine and biology, 2017

Until the beginning of the 1980s, nitric oxide (NO) was just a toxic molecule of a lengthy list o... more Until the beginning of the 1980s, nitric oxide (NO) was just a toxic molecule of a lengthy list of environmental pollutants such as cigarette smoke and smog. In fact, NO had a very bad reputation of being destroyer of ozone, suspected carcinogen and precursor of acid rain. However, by the early 1990s it was well recognized by the medical research community. Over the last two decades, the picture has been totally changed. Diverse lines of evidence have converged to show that this sometime poison is a fundamental player in the everyday business of the human body. NO activity was probed in the brain, arteries, immune system, liver, pancreas, uterus, peripheral nerves, lungs, and almost every system in the human body. NO is a major player in the cardiovascular system as it is involved in regulating blood pressure. In the CNS, it is involved in memory formation and the regulation of cerebral blood flow to ensure adequate supply of blood to the brain. Because NO is involved in many pathwa...

Research paper thumbnail of The Role of Systemic Inflammation, Nitric Oxide Signaling, and NMDA Receptors in an Experimental Model of Alzheimer’s Disease

Alzheimer’s disease is (AD) a common form of age-related dementia, characterized by deposition of... more Alzheimer’s disease is (AD) a common form of age-related dementia, characterized by deposition of amyloid A plaques, neuroinflammation and neurodegeneration. Nitric oxide (NO) signaling has been involved in related neuronal processes: NO is involved in memory development and neuroinflammation, neuronal NO synthase (nNOS) is believed to contribute to memory formation, while inducible NO synthase (iNOS) mediates inflammatory processes in the CNS. Here, we study the contribution of LPS-induced systemic inflammation, as well as the role of NO signaling on incidence and progression of induced AD, and whether L-arginine can ameliorate AD-related dysfunctions. AD was induced in mice by a single dose of lipopolysaccharide (LPS). Behavioral tests for spatial and non-spatial memory and locomotor activity were performed to assess disease severity and progression. The effects of L-NAME (general NOS inhibitor), 1400W (iNOS inhibitor), Diflunisal (systemic anti-inflammatory drug that does not cr...

Research paper thumbnail of Detection of Pulmonary Embolism on CT-Angiography Using Contrast Attenuation of Pulmonary Veins

Acta Angiologica, 2021

Introduction: In areas of pulmonary embolism (PE), the enhancement of pulmonary veins on computed... more Introduction: In areas of pulmonary embolism (PE), the enhancement of pulmonary veins on computed tomography pulmonary angiography (CTPA) should be decreased due to reduced arterial perfusion. The purpose of this study was to investigate the accuracy of contrast density measurements (differences) in all pulmonary veins and the left atrium for the prediction of PE. Material and methods: Seventy-five patients with PE and 22 patients without PE on CTPA were included. Four readers measured the enhancement of the blood in the pulmonary vein immediately before the entrance to the left atrium, right after the aperture, in the center of the left atrium, in the pulmonary trunk and in the aorta. Enhancement of the pulmonary veins with and without upstream PE, and ROC curves with HU thresholds for optimal sensitivity and specificity for PE were calculated. Results: More PEs were found in the right and lower lobes. PE-affected lobes demonstrated 13.8 ± 45 HU less enhancement in the pulmonary vein, compared to a paired non-affected pulmonary vein of the same patient (P < 0.0001). On average, non-affected pulmonary veins demonstrated no difference in enhancement compared to each other: 0.2 ± 21 HU. The optimal cutoff level in the ROC curve analysis for PE affection proved to be decreasing enhancement in the pulmonary vein of more than 10 HU compared to the atrium. Conclusion: Decreasing enhancement in the pulmonary vein of more than 10 HU compared to the atrium could provide additional information and confidence in the diagnosis of PE.