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Genes Oct 2022Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases.... (Review)
Review
Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases. In this review, we examine 25 selected hereditary metabolic bone diseases and recognized genetic variations of 78 genes that represent each of the three groups, including sclerosing bone disorders, disorders of defective bone mineralization and disorder of bone matrix and cartilage formation. We also review pathophysiology, manifestation and treatment for each disease. Advances in molecular genetics and basic sciences has led to accurate genetic diagnosis and novel effective therapeutic strategies for some diseases. For other diseases, the genetic basis and pathophysiology remain unclear. Further researches are therefore crucial to innovate ways to overcome diagnostic challenges and develop effective treatment options for these orphan diseases.
Topics: Humans; Bone Diseases, Metabolic; Rare Diseases
PubMed: 36292765
DOI: 10.3390/genes13101880 -
European Journal of Nutrition Jun 2023In addition to the role of vitamin D in bone mineralization, calcium and phosphate homeostasis, and skeletal health, evidence suggests an association between vitamin D... (Review)
Review
BACKGROUND
In addition to the role of vitamin D in bone mineralization, calcium and phosphate homeostasis, and skeletal health, evidence suggests an association between vitamin D deficiency and a wide range of chronic conditions. This is of clinical concern given the substantial global prevalence of vitamin D deficiency. Vitamin D deficiency has traditionally been treated with vitamin D (cholecalciferol) or vitamin D (ergocalciferol). Calcifediol (25-hydroxyvitamin D) has recently become available more widely.
METHODS
By means of targeted literature searches of PubMed, this narrative review overviews the physiological functions and metabolic pathways of vitamin D, examines the differences between calcifediol and vitamin D, and highlights clinical trials conducted with calcifediol in patients with bone disease or other conditions.
RESULTS
For supplemental use in the healthy population, calcifediol can be used at doses of up to 10 µg per day for children ≥ 11 years and adults and up to 5 µg/day in children 3-10 years. For therapeutic use of calcifediol under medical supervision, the dose, frequency and duration of treatment is determined according to serum 25(OH)D concentrations, condition, type of patient and comorbidities. Calcifediol differs pharmacokinetically from vitamin D in several ways. It is independent of hepatic 25-hydroxylation and thus is one step closer in the metabolic pathway to active vitamin D. At comparable doses to vitamin D, calcifediol achieves target serum 25(OH)D concentrations more rapidly and in contrast to vitamin D, it has a predictable and linear dose-response curve irrespective of baseline serum 25(OH)D concentrations. The intestinal absorption of calcifediol is relatively preserved in patients with fat malabsorption and it is more hydrophilic than vitamin D and thus is less prone to sequestration in adipose tissue.
CONCLUSION
Calcifediol is suitable for use in all patients with vitamin D deficiency and may be preferable to vitamin D for patients with obesity, liver disease, malabsorption and those who require a rapid increase in 25(OH)D concentrations.
Topics: Adult; Child; Humans; Calcifediol; Dietary Supplements; Vitamin D; Vitamins; Cholecalciferol; Vitamin D Deficiency
PubMed: 36862209
DOI: 10.1007/s00394-023-03103-1 -
The British Journal of Radiology Jan 2019The concept of tumour hypoxia as a cause of radiation resistance has been prevalent for over 100 years. During this time, our understanding of tumour hypoxia has matured... (Review)
Review
The concept of tumour hypoxia as a cause of radiation resistance has been prevalent for over 100 years. During this time, our understanding of tumour hypoxia has matured with the recognition that oxygen tension within a tumour is influenced by both diffusion and perfusion mechanisms. In parallel, clinical strategies to modify tumour hypoxia with the expectation that this will improve response to radiation have been developed and tested in clinical trials. Despite many disappointments, meta-analysis of the data on hypoxia modification confirms a significant impact on both tumour control and survival. Early trials evaluated hyperbaric oxygen followed by a generation of studies testing oxygen mimetics such as misonidazole, pimonidazole and etanidazole. One highly significant result stands out from the use of nimorazole in advanced laryngeal cancer with a significant advantage seen for locoregional control using this radiosensitiser. More recent studies have evaluated carbogen and nicotinamide targeting both diffusion related and perfusion related hypoxia. A significant survival advantage is seen in muscle invasive bladder cancer and also for locoregional control in hypopharygeal cancer associated with a low haemoglobin. New developments include the recognition that mitochondrial complex inhibitors reducing tumour oxygen consumption are potential radiosensitising agents and atovaquone is currently in clinical trials. One shortcoming of past hypoxia modifying trials is the failure to identify oxygenation status and select those patient with significant hypoxia. A range of biomarkers are now available including histological necrosis, immunohistochemical intrinsic markers such as CAIX and Glut 1 and hypoxia gene signatures which have been shown to predict outcome and will inform the next generation of hypoxia modifying clinical trials.
Topics: Animals; Cell Hypoxia; Female; Humans; Male; Misonidazole; Neoplasms; Niacinamide; Oxygen Consumption; Radiation-Sensitizing Agents; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis; Treatment Outcome; Tumor Hypoxia
PubMed: 29979089
DOI: 10.1259/bjr.20170966 -
Biomolecules Oct 2021Tumour hypoxia is significantly correlated with patient survival and treatment outcomes. At the molecular level, hypoxia is a major driving factor for tumour progression... (Review)
Review
Tumour hypoxia is significantly correlated with patient survival and treatment outcomes. At the molecular level, hypoxia is a major driving factor for tumour progression and aggressiveness. Despite the accumulative scientific and clinical efforts to target hypoxia, there is still a need to find specific treatments for tumour hypoxia. In this review, we discuss a variety of approaches to alter the low oxygen tumour microenvironment or hypoxia pathways including carbogen breathing, hyperthermia, hypoxia-activated prodrugs, tumour metabolism and hypoxia-inducible factor (HIF) inhibitors. The recent advances in technology and biological understanding reveal the importance of revisiting old therapeutic regimens and repurposing their uses clinically.
Topics: Animals; Humans; Prodrugs; Tumor Hypoxia
PubMed: 34827602
DOI: 10.3390/biom11111604 -
Nutrients Feb 2022It is remarkable how an invisible, inanimate particle-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19)-that is hell-bent on reproducing itself was...
It is remarkable how an invisible, inanimate particle-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19)-that is hell-bent on reproducing itself was able to bring our modern civilization to its knees [...].
Topics: COVID-19; Humans; SARS-CoV-2
PubMed: 35267938
DOI: 10.3390/nu14050963 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... Apr 2022Bone fractures and fracture healing are one of the most common problems among orthopedic surgeons. In this study, we investigated the effects of hyperbaric oxygen (HBO)...
BACKGROUND
Bone fractures and fracture healing are one of the most common problems among orthopedic surgeons. In this study, we investigated the effects of hyperbaric oxygen (HBO) and carbogen (C) treatment on fracture healing in the experimental animal model.
METHODS
Twenty-four male Wistar-Albino rats were randomly divided into three groups as Group 1 (C inhalation therapy), Group 2 (HBO inhalation therapy), and Group 3 (control group), with eight rats in each group. HBO and C treatment were given to the rats in Group 1 and Group 2 1 week before the surgical procedure and 3 weeks after the surgical procedure. Following the surgical procedure, all rats were killed at the end of the 3rd week and the healing tissue in the fracture line was evaluated clinically, radiologically, and histopathologically.
RESULTS
Although there were higher histopathological, radiological, and clinical scores in the HBO and C groups in terms of frac-ture healing compared to the control group, there was no statistically significant difference between the groups.
CONCLUSION
There are many studies in the literature that examine the systemic and local effects of HBO and C treatments and show that they increase tissue oxygenation. Our study showed that HBO and C groups had no beneficial or harmful effects on fracture healing compared to the control group.
Topics: Animals; Carbon Dioxide; Fracture Healing; Hyperbaric Oxygenation; Male; Oxygen; Rats; Rats, Wistar
PubMed: 35485502
DOI: 10.14744/tjtes.2021.02575 -
Magnetic Resonance in Medicine Jan 2009Magnetic resonance imaging has shown promise for evaluating tissue oxygenation. In this study differences in the tissue longitudinal relaxation rate (R(1)) and effective... (Comparative Study)
Comparative Study
Magnetic resonance imaging has shown promise for evaluating tissue oxygenation. In this study differences in the tissue longitudinal relaxation rate (R(1)) and effective transverse relaxation rate (R(*)(2)), induced by inhalation of pure oxygen and carbogen, were evaluated in 10 healthy subjects. Significant reductions in R(1) were demonstrated following both oxygen and carbogen inhalation in the spleen (both P < 0.001), liver (P = 0.002 air vs. oxygen; P = 0.001 air vs. carbogen), skeletal muscle (both P < 0.001), and renal cortex (P = 0.005 air vs. oxygen; P = 0.008 air vs. carbogen). No significant change in R(*)(2) occurred following pure oxygen in any organ. However, a significant increase in R(*)(2) was observed in the spleen (P < 0.001), liver (P = 0.001), skeletal muscle (P = 0.026), and renal cortex (P = 0.001) following carbogen inhalation, an opposite effect to that observed in many studies of tumor pathophysiology. Changes in R(1) and R(*)(2) were independent of the gas administration order in the spleen and skeletal muscle. These findings suggest that the R(1) and R(*)(2) responses to hyperoxic gases are independent biomarkers of oxygen physiology.
Topics: Administration, Inhalation; Adult; Algorithms; Carbon Dioxide; Female; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Metabolic Clearance Rate; Organ Specificity; Oxygen; Pattern Recognition, Automated; Reference Values; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution
PubMed: 19097212
DOI: 10.1002/mrm.21815 -
Journal of Cerebral Blood Flow and... May 2022Blood oxygenation level-dependent (BOLD) or arterial spin labeling (ASL) MRI with hypercapnic stimuli allow for measuring cerebrovascular reactivity (CVR). Hypercapnic...
Blood oxygenation level-dependent (BOLD) or arterial spin labeling (ASL) MRI with hypercapnic stimuli allow for measuring cerebrovascular reactivity (CVR). Hypercapnic stimuli are also employed in calibrated BOLD functional MRI for quantifying neuronally-evoked changes in cerebral oxygen metabolism (CMRO). It is often assumed that hypercapnic stimuli (with or without hyperoxia) are iso-metabolic; increasing arterial CO or O does not affect CMRO. We evaluated the null hypothesis that two common hypercapnic stimuli, 'CO in air' and carbogen, are iso-metabolic. TRUST and ASL MRI were used to measure the cerebral venous oxygenation and cerebral blood flow (CBF), from which the oxygen extraction fraction (OEF) and CMRO were calculated for room-air, 'CO in air' and carbogen. As expected, CBF significantly increased (9.9% ± 9.3% and 12.1% ± 8.8% for 'CO in air' and carbogen, respectively). CMRO decreased for 'CO in air' (-13.4% ± 13.0%, p < 0.01) compared to room-air, while the CMRO during carbogen did not significantly change. Our findings indicate that 'CO in air' is not iso-metabolic, while carbogen appears to elicit a mixed effect; the CMRO reduction during hypercapnia is mitigated when including hyperoxia. These findings can be important for interpreting measurements using hypercapnic or hypercapnic-hyperoxic (carbogen) stimuli.
Topics: Adult; Brain; Carbon Dioxide; Cerebrovascular Circulation; Hemodynamics; Humans; Hypercapnia; Hyperoxia; Magnetic Resonance Imaging; Oxygen; Oxygen Consumption
PubMed: 34851757
DOI: 10.1177/0271678X211064572 -
The British Journal of Radiology Mar 2019Hypoxia is known to be a poor prognostic indicator for nearly all solid tumours and also is predictive of treatment failure for radiotherapy, chemotherapy, surgery and... (Review)
Review
Hypoxia is known to be a poor prognostic indicator for nearly all solid tumours and also is predictive of treatment failure for radiotherapy, chemotherapy, surgery and targeted therapies. Imaging has potential to identify, spatially map and quantify tumour hypoxia prior to therapy, as well as track changes in hypoxia on treatment. At present no hypoxia imaging methods are available for routine clinical use. Research has largely focused on positron emission tomography (PET)-based techniques, but there is gathering evidence that MRI techniques may provide a practical and more readily translational alternative. In this review we focus on the potential for imaging hypoxia by measuring changes in longitudinal relaxation [R; termed oxygen-enhanced MRI or tumour oxygenation level dependent (TOLD) MRI] and effective transverse relaxation [R*; termed blood oxygenation level dependent (BOLD) MRI], induced by inhalation of either 100% oxygen or the radiosensitising hyperoxic gas carbogen. We explain the scientific principles behind oxygen-enhanced MRI and BOLD and discuss significant studies and their limitations. All imaging biomarkers require rigorous validation in order to translate into clinical use and the steps required to further develop oxygen-enhanced MRI and BOLD MRI into decision-making tools are discussed.
Topics: Biomarkers; Contrast Media; Humans; Magnetic Resonance Imaging; Neoplasms; Oxygen; Tumor Hypoxia
PubMed: 30272998
DOI: 10.1259/bjr.20180642 -
Clinical and Translational Radiation... Nov 2021Bladder preservation with trimodality treatment (TMT) is an alternative strategy to radical cystectomy (RC) for the management of localised muscle invasive bladder... (Review)
Review
Bladder preservation with trimodality treatment (TMT) is an alternative strategy to radical cystectomy (RC) for the management of localised muscle invasive bladder cancer (MIBC). TMT comprises of transurethral resection of the bladder tumour (TURBT) followed by radiotherapy with concurrent radiosensitisation. TMT studies have shown neo-adjuvant chemotherapy with cisplatin-based regimens is often given to further improve survival outcomes. A hypofractionated radiotherapy regimen is preferable due to its non-inferiority in local control and late toxicities. Radiosensitisation can comprise concurrent chemotherapy (with gemcitabine, cisplatin or combination fluorouracil and mitomycin), CON (carbogen and nicotinomide) or hyperthermic treatment. Radiotherapy techniques are continuously improving and becoming more personalised. As the bladder is a mobile structure subject to volumetric changes from filling, an adaptive approach can optimise bladder coverage and reduce dose to normal tissue. Adaptive radiotherapy (ART) is an evolving field that aims to overcome this. Improved knowledge of tumour biology and advances in imaging techniques aims to further optimise and personalise treatment.
PubMed: 34466667
DOI: 10.1016/j.ctro.2021.08.003