scholarly journals In Vivo Calcium and Phosphate Iontophoresis for the Topical Treatment of Osteoporosis

2012 ◽  
Vol 92 (2) ◽  
pp. 289-297 ◽  
Author(s):  
Izabella Gomez ◽  
Andrea Szabó ◽  
Lajos Pap ◽  
Lajos Pap ◽  
Krisztina Boda ◽  
...  

Background In addition to systemic treatment, osteoporosis may be treated topically by incorporating calcium and phosphate into the bone. Objective This article describes the use of a recently developed, novel iontophoretic apparatus suitable for local ion delivery into bones. In this study, in vivo experiments were performed to compare the effects of local electrotherapy and those of systemic hormone replacement on bone. Design In this study, local iontophoresis was carried out in ovariectomized and control rats. Bone density, biomechanical, and elemental studies were performed. Methods Forty 12-week-old Sprague-Dawley rats received an ovariectomy (OVX) or were sham-operated (sham). Twenty-one weeks later, tibias of subgroups of sham-operated and OVX animals were subjected to serial local iontophoresis (IOP) treatments, received systemic subcutaneous 17β-estradiol (E2), or were treated with the combination of IOP and E2. Changes in bone density were detected by quantitative ultrasound densitometry and expressed as amplitude-dependent speed of sound (AD-SoS). Biomechanical studies and elemental analysis were performed at the end of the experiments. Results Osteopenia developed 21 weeks after OVX in the proximal tibial regions; the mean difference estimate (95% confidence intervals) of AD-SoS values between the sham-operated and OVX animals was 188.7 (140.4–237.1). Serial iontophoretic treatment resulted in an increase in bone density in both sham-operated and OVX animals (sham+IOP versus sham: 121.4 [73.01–169.7]; OVX+IOP versus OVX: 241.6 [193.2–289.9]). Similar changes in AD-SoS were detected after 17β-estradiol (E2) treatment; however, even greater changes occurred after OVX+E2+IOP versus OVX+E2 (123.4 [75.1–171.8]). Similar improvements also were evident regarding the biomechanical features of the tibias. Limitations A limitation of this study was the relatively small number of rats. Conclusions The efficacy of local IOP using calcium- and phosphate-donating microparticles is comparable to that of estrogen therapy as evidenced by steadily increasing bone density, restoration of the calcium and phosphate balance, and improvement in the biomechanical properties of the bone.

Author(s):  
John R Burnett ◽  
Samuel D Vasikaran

Atherosclerotic heart disease and osteoporosis are both diseases of old age. Evidence is accumulating for a link between vascular and bone disease. Calcification is a common feature of atherosclerotic plaques, and osteoporosis is associated with both atherosclerosis and vascular calcification. However, the relationship of vascular calcification to the pathogenesis of atherosclerosis remains incompletely understood. Hormone replacement therapy has beneficial effects in the prevention of both atherosclerosis and osteoporosis. Bisphosphonates inhibit bone resorption and are used in the treatment of osteoporosis, whereas the statins inhibit cholesterol biosynthesis and are used for the treatment of atherosclerosis. We have reviewed recent advances in the knowledge of the actions of bisphosphonates and statins at the cellular, molecular and end-organ levels in order to examine the relationship between cardiovascular disease and osteoporosis and to explore the link between lipids and bones. These studies suggest that the mechanism of actions of these two classes of drugs at the cellular level may not be mutually exclusive. There are some early clinical data to complement these findings, suggesting that statins increase bone density and bisphosphonates may have a beneficial effect in vivo on plasma lipid levels and on the atherosclerotic process. Properly designed prospective studies that examine the effect of statins on bone density and fractures, as well as the effects of bisphosphonates on lipid profiles, atherosclerotic progression and cardiovascular morbidity and mortality are needed to define clearly the clinical effects and potential new roles for these agents.


2020 ◽  
pp. 155335062097800
Author(s):  
Ian A. Makey ◽  
Nitin A. Das ◽  
Samuel Jacob ◽  
Magdy M. El-Sayed Ahmed ◽  
Colleen M. Makey ◽  
...  

Background. Retained hemothorax (RH) is a common problem in cardiothoracic and trauma surgery. We aimed to determine the optimum agitation technique to enhance thrombus dissolution and drainage and to apply the technique to a porcine-retained hemothorax. Methods. Three agitation techniques were tested: flush irrigation, ultrasound, and vibration. We used the techniques in a benchtop model with tissue plasminogen activator (tPA) and pig hemothorax with tPA. We used the most promising technique vibration in a pig hemothorax without tPA. Statistics. We used 2-sample t tests for each comparison and Cohen d tests to calculate effect size (ES). Results. In the benchtop model, mean drainages in the agitation group and control group and the ES were flush irrigation, 42%, 28%, and 2.91 ( P = .10); ultrasound, 35%, 27%, and .76 ( P = .30); and vibration, 28%, 19%, and 1.14 ( P = .04). In the pig hemothorax with tPA, mean drainages and the ES of each agitation technique compared with control (58%) were flush irrigation, 80% and 1.14 ( P = .37); ultrasound, 80% and 2.11 ( P = .17); and vibration, 95% and 3.98 ( P = .06). In the pig hemothorax model without tPA, mean drainages of the vibration technique and control group were 50% and 43% (ES = .29; P = .65). Discussion. In vitro studies suggested flush irrigation had the greatest effect, whereas only vibration was significantly different vs the respective controls. In vivo with tPA, vibration showed promising but not statistically significant results. Results of in vivo experiments without tPA were negative. Conclusion. Agitation techniques, in combination with tPA, may enhance drainage of hemothorax.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Michael DeLong ◽  
Mauricio Gil-Silva ◽  
Veronica Minsu Hong ◽  
Olivia Babyok ◽  
Benedict J. Kolber

Abstract Background The regulation and control of pressure stimuli is useful for many studies of pain and nociception especially those in the visceral pain field. In many in vivo experiments, distinct air and liquid stimuli at varying pressures are delivered to hollow organs such as the bladder, vagina, and colon. These stimuli are coupled with behavioral, molecular, or physiological read-outs of the response to the stimulus. Care must be taken to deliver precise timed stimuli during experimentation. For example, stimuli signals can be used online to precisely time-lock the stimulus with a physiological output. Such precision requires the development of specialized hardware to control the stimulus (e.g., air) while providing a precise read-out of pressure and stimulus signal markers. Methods In this study, we designed a timed pressure regulator [termed visceral pressure stimulator (VPS)] to control air flow, measure pressure (in mmHg), and send stimuli markers to online software. The device was built using a simple circuit and primarily off-the-shelf parts. A separate custom inline analog-to-digital pressure converter was used to validate the real pressure output of the VPS. Results Using commercial physiological software (Spike2, CED), we were able to measure mouse bladder pressure continuously during delivery of unique air stimulus trials in a mouse while simultaneously recording an electromyogram (EMG) of the overlying abdominal muscles. Conclusions This device will be useful for those who need to (1) deliver distinct pressure stimuli while (2) measuring the pressure in real-time and (3) monitoring stimulus on–off using physiological software.


2013 ◽  
Vol 135 (10) ◽  
Author(s):  
Clare Y. L. Chao ◽  
Gabriel Y. F. Ng ◽  
Kwok-Kuen Cheung ◽  
Yong-Ping Zheng ◽  
Li-Ke Wang ◽  
...  

An evaluation of wound mechanics is crucial in reflecting the wound healing status. The present study examined the biomechanical properties of healing rat skin wounds in vivo and ex vivo. Thirty male Sprague-Dawley rats, each with a 6 mm full-thickness circular punch biopsied wound at both posterior hind limbs were used. The mechanical stiffness at both the central and margins of the wound was measured repeatedly in five rats over the same wound sites to monitor the longitudinal changes over time of before wounding, and on days 0, 3, 7, 10, 14, and 21 after wounding in vivo by using an optical coherence tomography-based air-jet indentation system. Five rats were euthanized at each time point, and the biomechanical properties of the wound tissues were assessed ex vivo using a tensiometer. At the central wound bed region, the stiffness measured by the air-jet system increased significantly from day 0 (17.2%), peaked at day 7 (208.3%), and then decreased progressively until day 21 (40.2%) as compared with baseline prewounding status. The biomechanical parameters of the skin wound samples measured by the tensiometer showed a marked reduction upon wounding, then increased with time (all p < 0.05). On day 21, the ultimate tensile strength of the skin wound tissue approached 50% of the normal skin; while the stiffness of tissue recovered at a faster rate, reaching 97% of its prewounded state. Our results suggested that it took less time for healing wound tissues to recover their stiffness than their maximal strength in rat skin. The stiffness of wound tissues measured by air-jet could be an indicator for monitoring wound healing and contraction.


2006 ◽  
Vol 12 (1_suppl) ◽  
pp. 4-7 ◽  
Author(s):  
Malcolm Whitehead

A new form of continuous combined hormone replacement therapy has become available that contains estradiol and drospirenone as the progestogen component. Drospirenone is a synthetic progestogen, the only one in hormone replacement therapy in the UK that possesses clinically relevant anti-mineralocorticoid activity. The combination of estradiol and drospirenone has been shown to provide relief from estrogen-deficiency symptoms of the menopause. It also helps to prevent osteoporosis in postmenopausal women by increasing bone density. Further, it has been shown to provide protection against endometrial hyperplasia associated with unopposed estrogen therapy.


2020 ◽  
Author(s):  
Emily A. McGlade ◽  
Gerardo G. Herrera ◽  
Kalli K. Stephens ◽  
Sierra L. W. Olsen ◽  
Sarayut Winuthayanon ◽  
...  

AbstractOne of the endogenous estrogens, 17β-estradiol (E2) is a female steroid hormone secreted from the ovary. It is well established that E2 causes biochemical and histological changes in the uterus. The oviduct response to E2 is virtually unknown in an in vivo environment. In this study, we assessed the effect of E2 on each oviductal cell type, using an ovariectomized-hormone-replacement mouse model, single cell RNA-sequencing (scRNA-seq), in situ hybridization, and cell-type-specific deletion in mice. We found that each cell type in the oviduct responded to E2 distinctively, especially ciliated and secretory epithelial cells. The treatment of exogenous E2 did not drastically alter the transcriptomic profile from that of endogenous E2 produced during estrus. Moreover, we have identified and validated genes of interest in our datasets that may be used as cell- and region-specific markers in the oviduct. Insulin-like growth factor 1 (Igf1) was characterized as an E2-target gene in the mouse oviduct and was also expressed in human Fallopian tubes. Deletion of Igf1 in progesterone receptor (Pgr)-expressing cells resulted in female subfertility, partially due to an embryo developmental defect and embryo retention within the oviduct. In summary, we have shown that oviductal cell types are differentially regulated by E2 and support gene expression changes that are required for normal embryo development and transport in mouse models.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Tong Wang ◽  
Wanchun Tang ◽  
Shijie Sun ◽  
Min-shan Tsai ◽  
Max Harry Weil

Background: In settings of heart failure, infusion of bone marrow mesenchymal stem cells (MSCs) improves myocardial function both in experimental and clinical studies. The mechanism by which MSCs improve myocardial function remains unknown. Hypothesis: MSCs may differentiate into beating myocytes in vivo. The contractility of these cells is comparable with those of myocytes. Methods: A thoracotomy was performed in 10 male Sprague-Dawley rats, weighing 350 – 450g. Myocardial infarction was induced by ligation of the left anterior descending artery (LAD). One week later, animals were randomized to receive 5×10 6 MSCs marked with PKH26 in phosphate buffer solution (PBS) or as a PBS bolus injection into local infarcted myocardium. Six weeks after the MSCs or PBS injection, the hearts were harvested and digested with collagease type II and single cardiomyocytes were obtained. PKH26 labeled myocytes differentiating from MSCs were observed with a microscope Olympus I×71. The contractility of labeled and unlabeled beating cells in MSCs-treated animals was compared. The contractility of unlabeled myocytes was compared between MSCs-treated and control groups. Result: The beating fluorescent labeled myocytes can be found in MSCs-treated animals [(1.2±0.4) ×10 6 ] and contractility of these cells were the same as that of unlabeled beating myocytes (Table 1 ). The contractility of unlabeled myocytes, however, was significantly better in MSCs-treated animals. Conclusion: MSCs could differentiate into the beating myocytes. However, this may not be the sole mechanism of improved myocardial function. Table 1 Cells contractility (%)


2019 ◽  
Vol 3 (11) ◽  
Author(s):  
Julie A Cakebread ◽  
Olivia A M Wallace ◽  
Marlena C Kruger ◽  
Mark H Vickers ◽  
Alison J Hodgkinson

ABSTRACT Background Nondairy beverages, produced from soy, rice, oat, almond, or coconut, are increasingly being used as alternatives to dairy milk, with the perception that they are healthier and/or more sustainable products than dairy products. Objective The aim of this study was to compare the effects of supplementing either bovine milk, soy, or almond-based beverages to young, growing rats fed an intact-protein diet or a diet that had protein substituted with amino acids (AA-diet). Methods Three-week-old male Sprague-Dawley rats were randomly assigned to 5 groups (n = 10/group) and fed ad libitum for 4 wk. Two control groups were fed either standard AIN-93G food [20% casein (CN) protein] or AIN-93G with amino acids (AAs) equivalent to CN protein, and water to drink. Three treatment groups were fed AIN-93G AA and supplemented with either bovine ultra-heat treatment (UHT) milk or soy or almond UHT beverages. Rat weight gain and food intakes were recorded. During week 4, body composition was assessed using DEXA to determine lean soft tissue, fat, and bone mass. At trial end, bone biomechanical properties and blood plasma mineral concentrations were measured. Results At the end of the trial, animals supplemented with almond beverage were lightest (P > 0.05), with higher plasma calcium concentrations (P > 0.05) and lower bone mineral content (BMC) and bone density (P > 0.05) than animals supplemented with milk or soy beverage. Soy-supplemented animals had similar BMC and bone density compared with milk-supplemented animals, although the soy group gained most weight (P > 0.05) and had the highest fat:lean ratio (P > 0.05) compared with other groups. Conclusions In the model tested, supplementing rats with bovine UHT milk and soy UHT beverage provided favorable bone health outcomes. Conversely, almond UHT beverage was not an effective supplement and could be detrimental to bone mineralization and strength outcomes.


1994 ◽  
Vol 266 (1) ◽  
pp. G118-G122
Author(s):  
E. Bergamini ◽  
A. Del Roso ◽  
Z. Gori ◽  
P. Masiello ◽  
M. Masini ◽  
...  

Regulation of liver macroautophagy and protein degradation by hormones and direct regulatory amino acids were studied in male 2-mo-old Sprague-Dawley albino rats with the use of the antilipolytic agent 3,5'-dimethylpyrazole (DMP; 12 mg/kg body wt ip) as a stimulatory agent. Injection of DMP decreased glutamine plasma levels and glutamine release from the perfused liver. Autophagic vacuoles were observed in the pericanalicular area of liver cells after 30 min. Levels and release of other regulatory amino acids did not exhibit any significant decrease but subsequently increased. Intraperitoneal administration of glutamine inhibited the proteolytic response. In conclusion, these studies demonstrate that in vivo induction and control of liver macroautophagy and protein degradation by the physiological mechanism (i.e., by shortage of nutrients) involve unbalanced and asynchronous changes in the levels of selected direct regulatory amino acids (i.e., a decrease in glutamine and a subsequent increase in leucine and tyrosine levels)


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3567-3567
Author(s):  
Tatiana Ulyanova ◽  
Gregory V. Priestley ◽  
Yi Jiang ◽  
Stephen Padilla ◽  
Thalia Papayannopoulou

Abstract Previous experiments in vitro have emphasized the important role of a5b1 integrin/fibronectin interactions in terminal stages of erythroid differentiation (JCB1987, 105:3105), whereas in vivo experiments with genetically deficient mice (JI2000, 165:4667) and recent in vitro ones emphasized the important contribution of a4b1 integrin in the expansion of fetal erythroid progenitors (JCB2007, 177:871) or for optimal responses post stress in adult animals (MCB2003, 23:9349). However, no abnormalities in erythropoiesis were reported in a model of conditional ablation of b1 integrins post-transplantation (Blood2006, 108:1857). Therefore, it has not been clear to what extent each of the two major b1 integrins (a4b1 and a5b1) alone or in combination is critical for expansion and/or terminal erythroid differentiation of adult cells at homeostasis and/or after stress. We have made detailed and parallel observations comparing erythropoiesis in two genetic models with conditional ablation of b1 or a4 integrins at homeostasis and after phenylhydrazine (PHZ)-mediated stress. Basal erythropoiesis in b1-, a4-deficient and control mice as assessed by hematocrit levels and total nucleated erythroid cells (Ter119+) in BM and spleen was similar. Furthermore, both b1 and a4-deficient mice showed an increase in circulating progenitors (1275±230 CFC/ml PB, 2446±256 CFC/ml PB, respectively) over controls (338±113 CFC/ml PB). However, post PHZ-induced hemolytic stress there was a dramatic difference in outcomes of b1-deficient, but modest differences in a4-deficient mice compared to controls. Survival of b1-deficient mice by day 6 post PHZ was 33% compared to 100% in a4-deficient and control groups. In b1-deficient animals, no significant increase in spleen cellularity (153±26×106 and194±64×106 cells/spleen at day 0 and 6 post PHZ, respectively) was detected and the expansion of total erythroid precursors (CD71hi,Ter119+) in the spleen was minimal (from 2.08×106 to 10.8×106 cells/spleen at day 6). In contrast, in a4-deficient and control mice by the same time spleen cellularity increased respectively by 3 and 8 fold, and erythroid precursors expanded by 400 and 2,500 fold. Of interest, BM response to PHZ was not significantly different among all groups. To test whether the splenic response was cell-autonomous or environmentally controlled we compared PHZ response in wild type recipients reconstituted with b1-ablated (Cre+b1D/D) or with control (Cre-b1f/f) BM cells. Recipients of b1-ablated cells had an impaired response compared to recipients of control cells, which was somewhat intermediate to that seen in non-transplanted b1-deficient animals; by day 6 post PHZ, spleen cellularity was 300±24×106 cells/spleen and erythroid precursors expanded by 130 fold in recipients of b1-ablated BM cells compared to 859±159×106 cells/spleen and 900 fold precursor increase in control recipients. These data suggest that both erythroid and their environmental cells were responsible for the reduced survival and poor spleen response in b1-deficient mice. The target environmental cells (fibroblasts, endothelial cells, macrophages) and/or matrix involved will be the focus of future studies. It is of interest that in contrast to splenic response, the increased release of progenitors from BM seen in animals reconstituted with b1D/D cells was as high as that seen in non-transplanted b1- deficient animals and with the same qualitative characteristics, suggesting this alteration in biodistribution of progenitors is cell autonomous. Taken together, our data suggest that a combined expression of b1 integrins in erythroid and cells in their microenvironment is critical for survival and optimal splenic response to a PHZ-induced stress in adult mice; release of progenitors seen at homeostasis in both b1 and a4 models is cell autonomous with a preferential erythroid progenitor release from BM seen only in b1-deficient but not in a4-deficient mice; in contrast to results with fetal liver cells showing a critical role of a4b1 but not a5b1 integrin for proliferative expansion of erythroid cells, in adults a5b1 expression in erythroid and environmental cells in the spleen assumes a more critical role. Our data expand the current knowledge on the distinct dependency of a4b1 vs a5b1 integrins in basal vs stress erythropoiesis and bridge previously divergent information from in vitro and in vivo experiments.


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