scholarly journals Effects of long-term administration of vitamin D3 analogs to mice

2000 ◽  
Vol 165 (1) ◽  
pp. 163-172 ◽  
Author(s):  
EA Smith ◽  
EP Frankenburg ◽  
SA Goldstein ◽  
K Koshizuka ◽  
E Elstner ◽  
...  

This study explores the effects of chronic administration of vitamin D(3) compounds on several biological functions in mice. Knowledge of long-term tolerability of vitamin D(3) analogs may be of interest in view of their potential clinical utility in the management of various pathologies such as malignancies, immunological disorders and bone diseases. Four unique vitamin D(3) analogs (code names, compounds V, EO, LH and LA) and 1,25-dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)) were administered i.p. for 55 weeks to Balb/c mice. Each analog had previously been shown to have potent in vitro activities. After 55 weeks of administration, the mice had a profound decrease in their serum levels of interleukin-2 (IL-2). Likewise, several analogs depressed serum immunoglobulin G concentrations (compounds LH and LA), but levels of blood lymphocytes and splenic lymphocyte subsets (CD4, CD8 and CD19) were not remarkably depressed. The percent of committed myeloid hematopoietic stem cells was 4- to 5-fold elevated in the bone marrow of the mice that received analogs LH and V; nevertheless, their peripheral blood white and red cell counts and platelets were not significantly different in any of the groups. The mice that received 1,25(OH)(2)D(3) had a decrease in bone quantity and quality with a decrease in cross-sectional area and cortical thickness, and a 50% reduction in both stiffness and failure load compared with the control group. In contrast, the cohort that received a fluorinated analog (compound EO) developed bones with significantly larger cross-sectional area and cortical thickness as well as stronger mechanical properties compared with the control group. At the conclusion of the study, body weights were significantly decreased in all experimental mice. Their blood chemistries were normal. Extensive gross and microscopic autopsy analyses of the mice at the conclusion of the study were normal, including those of their kidneys. In conclusion, the vitamin D(3) analogs were fairly well tolerated. They did suppress immunity as measured by serum IL-2 and may provide a means to depress the immune response after organ transplantation and for autoimmune diseases. Use of these analogs prevented the detrimental effects of vitamin D(3) administration on mechanical and geometric properties of bone, while one analog (compound EO) actually enhanced bone properties. These results suggest that long-term clinical trials with the analogs are feasible.

2018 ◽  
Vol 36 (5) ◽  
pp. 327-332
Author(s):  
Miwa Imaeda ◽  
Tatsuya Hojo ◽  
Hiroshi Kitakoji ◽  
Kazuto Tanaka ◽  
Megumi Itoi ◽  
...  

Aims In this study we examined the effect of electroacupuncture (EA) stimulation on the mechanical strength of the rat Achilles tendon after long-term recovery. Methods Using 20 rats, an Achilles tendon rupture model was created in an invasive manner. The rats were assigned to one of three groups, that received EA treatment (EA group), minimal acupuncture (MA group) or remained untreated (Control group). In the EA group, EA stimulation (5 ms, 50 Hz, 20 µA, 20 min) was applied to the rupture region over a period of 90 days (five times/week). In the MA group, needles were inserted into the same positions as in the EA group but no electrical current was applied. After 90 days the tendon was measured to calculate the cross-sectional area of the rupture region. Then, the mechanical strength of the tendon was measured by tensile testing. Results No significant differences were observed between the three groups in cross-sectional area of the injured tendon. For maximum breaking strength, the EA group showed a significantly higher threshold compared with the Control group (P<0.05) but not the MA group (P=0.24). No significant difference was seen between the MA group and the Control group (P=0.96). Conclusion Given the EA group showed a significant increase in maximum breaking strength, it is likely that EA stimulation increases the mechanical strength of a repaired tendon after long-term recovery, and EA stimulation could be useful for preventing re-rupture.


2020 ◽  
Author(s):  
Shivam Mehta ◽  
Dennis Wang ◽  
Chia-Ling Kuo ◽  
Jinjian Mu ◽  
Manuel Lagravere Vich ◽  
...  

ABSTRACT Objectives To evaluate the long-term effects on airway in patients with mini-screw–assisted rapid palatal expansion (MARPE), rapid palatal expansion (RPE), and controls with three-dimensional cone-beam computed tomography (CBCT) analysis. Materials and Methods A total of 180 CBCTs of 60 patients were analyzed at different time points, such as pretreatment, postexpansion, and posttreatment. Patients were divided into three groups: mini-screw assisted rapid palatal expansion (MARPE), rapid palatal expansion (RPE), and controls. The nasal cavity, nasopharyngeal, oropharyngeal, and laryngopharyngeal airway volume and area were measured. Changes in total airway volume, total airway area, minimal cross-sectional area, maxillary intermolar width, external maxillary width, and palatal width were also evaluated. Results Both MARPE and RPE caused a statistically significant increase in the airway after expansion as compared with the control group, but there was no statistically significant difference in the change in airway between MARPE, RPE, and the control group at posttreatment, except for nasopharyngeal volume, which was significantly increased in the MARPE group. There was no correlation between the amount of expansion and increase in total airway volume. Conclusions There was a significant increase in total airway volume, total airway area, and minimal cross-sectional area with MARPE and RPE immediately after expansion, but at posttreatment, the changes in the MARPE and RPE groups were similar to the change in the control group. However, MARPE led to a significant long-term increase in nasopharyngeal volume. The amount of expansion did not correlate with the increase in pharyngeal airway volume.


Author(s):  
T.I. Kuznetsova

The aim of the paper is to study the effect of long-term feeding with finely ground food on the dynamics of cytometric hepatocyte parameters in white rats in postnatal ontogenesis. Materials and Methods. On the 21st day of postnatal ontogenesis, 100 male white rats were divided into a control group and two experimental groups (experiment 1 and experiment 2). The animals of the control group were fed with natural food, while the animals of the experimental groups similar food (in terms of quality and quantity), but after careful mechanical grinding. To assess the reversibility of the homogenized food feeding, animals of experimental group 2 were fed natural food, as the control animals (days 120–240). The authors studied the liver, using cell morphometry of standard histological staining. They measured cross-sectional area of the nuclei and hepatocyte cytoplasm, calculated nuclear-cytoplasmic ratio, and counted the number of hepatocytes on the standard cross-sectional area, including binuclear hepatocytes. Results. It was revealed that long-term consumption of homogenized food affects the postnatal morphogenesis of the liver parenchyma. From the 21st to the 120th day, the growth rate of hepatocytes and the number of binuclear cells in the experimental animals exceeded those of the control animals, and from the 120th up to the 240th day, the growth rate of hepatocytes in the experimental animals was significantly inferior to that of the control animals. As a result, the number of cells per standard cutting area increased. In case of transition to normal food with natural mechanical properties (120th–240th days of postnatal ontogenesis) there was a tendency to the restoration of cytometric hepatocyte parameters. However, the authors did not observe complete recovery. Keywords: liver, hepatocyte, homogenized food. Цель работы – изучить влияние длительного питания мелко измельченной пищей на динамику цитометрических параметров гепатоцитов белых крыс в постнатальном онтогенезе. Материалы и методы. На 21-е сут постнатального онтогенеза 100 самцов белых крыс были разделены на контрольную и две опытные группы (опыт I и опыт II). Животных контрольной группы содержали на естественном для грызунов корме, а животные опытных групп получали аналогичную по качественному и количественному составу пищу, но после тщательного механического измельчения. Для оценки обратимости воздействия питания диспергированной пищей животных II опытной группы со 120-х по 240-е сут переводили на питание кормом контрольных животных. Исследовали участки печени, морфометрию клеток которой проводили на стандартно окрашенных гистологических срезах. Измеряли площадь сечения ядер и цитоплазмы гепатоцитов, вычисляли ядерно-цитоплазматическое отношение, на стандартной площади среза подсчитывали количество гепатоцитов, в т.ч. двуядерных. Результаты. Выявлено, что длительное потребление диспергированной пищи оказывает воздействие на постнатальный морфогенез паренхимы печени. С 21-х по 120-е сут интенсивность роста гепатоцитов и количество двуядерных клеток опытных животных превышает таковые значения контрольных, а с 120-х по 240-е сут интенсивность роста гепатоцитов опытных животных существенно уступает показателям контрольных животных, вследствие чего количество клеток на стандартную площадь среза увеличивается. При переходе к питанию пищей с естественными механическими свойствами со 120-х по 240-е сут постнатального онтогенеза наблюдается тенденция к восстановлению цитометрических параметров гепатоцитов, однако полного восстановления не происходит. Ключевые слова: печень, гепатоцит, диспергированная пища.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gernot Seppel ◽  
Andreas Voss ◽  
Daniel J. H. Henderson ◽  
Simone Waldt ◽  
Bernhard Haller ◽  
...  

Abstract Background While supraspinatus atrophy can be described according to the system of Zanetti or Thomazeau there is still a lack of characterization of isolated subscapularis muscle atrophy. The aim of this study was to describe patterns of muscle atrophy following repair of isolated subscapularis (SSC) tendon. Methods Forty-nine control shoulder MRI scans, without rotator cuff pathology, atrophy or fatty infiltration, were prospectively evaluated and subscapularis diameters as well as cross sectional areas (complete and upper half) were assessed in a standardized oblique sagittal plane. Calculation of the ratio between the upper half of the cross sectional area (CSA) and the total CSA was performed. Eleven MRI scans of patients with subscapularis atrophy following isolated subscapularis tendon tears were analysed and cross sectional area ratio (upper half /total) determined. To guarantee reliable measurement of the CSA and its ratio, bony landmarks were also defined. All parameters were statistically compared for inter-rater reliability, reproducibility and capacity to quantify subscapularis atrophy. Results The mean age in the control group was 49.7 years (± 15.0). The mean cross sectional area (CSA) was 2367.0 mm2 (± 741.4) for the complete subscapularis muscle and 1048.2 mm2 (± 313.3) for the upper half, giving a mean ratio of 0.446 (± 0.046). In the subscapularis repair group the mean age was 56.7 years (± 9.3). With a mean cross sectional area of 1554.7 mm2 (± 419.9) for the complete and of 422.9 mm2 (± 173.6) for the upper half of the subscapularis muscle, giving a mean CSA ratio of 0.269 (± 0.065) which was seen to be significantly lower than that of the control group (p < 0.05). Conclusion Analysis of typical atrophy patterns of the subscapularis muscle demonstrates that the CSA ratio represents a reliable and reproducible assessment tool in quantifying subscapularis atrophy. We propose the classification of subscapularis atrophy as Stage I (mild atrophy) in case of reduction of the cross sectional area ratio < 0.4, Stage II (moderate atrophy) in case of < 0.35 and Stage III (severe atrophy) if < 0.3.


2017 ◽  
Vol 16 (3) ◽  
pp. 214-219 ◽  
Author(s):  
Marta Gimunová ◽  
Martin Zvonař ◽  
Kateřina Kolářová ◽  
Zdeněk Janík ◽  
Ondřej Mikeska ◽  
...  

Abstract Background During pregnancy, a number of changes affecting venous blood flow occur in the circulatory system, such as reduced vein wall tension or increased exposure to collagen fibers. These factors may cause blood stagnation, swelling of the legs, or endothelial damage and consequently lead to development of venous disease. Objectives The aim of this study is to evaluate the effect of special footwear designed to improve blood circulation in the feet on venous blood flow changes observed during advancing phases of pregnancy. Methods Thirty healthy pregnant women participated in this study at 25, 30, and 35 weeks of gestation. Participants were allocated at random to an experimental group (n = 15) which was provided with the special footwear, or a control group (n = 15). At each data collection session, Doppler measurements of peak systolic blood flow velocity and cross-sectional area of the right popliteal vein were performed using a MySonoU6 ultrasound machine with a linear transducer (Samsung Medison). The differences were compared using Cohen’s d test to calculate effect size. Results With advancing phases of pregnancy, peak systolic velocity in the popliteal vein decreased significantly in the control group, whereas it increased significantly in the experimental group. No significant change in cross-sectional area was observed in any of the groups. Conclusions Findings in the experimental group demonstrated that wearing the footwear tested may prevent venous blood velocity from reducing during advanced phases of pregnancy. Nevertheless, there is a need for further investigation of the beneficial effect on venous flow of the footwear tested and its application.


2013 ◽  
Vol 114 (8) ◽  
pp. 998-1008 ◽  
Author(s):  
Mette Hansen ◽  
Christian Couppe ◽  
Christina S. E. Hansen ◽  
Dorthe Skovgaard ◽  
Vuokko Kovanen ◽  
...  

Sex differences exist with regards to ligament and tendon injuries. Lower collagen synthesis has been observed in exercising women vs. men, and in users of oral contraceptives (OC) vs. nonusers, but it is unknown if OC will influence tendon biomechanics of women undergoing regular training. Thirty female athletes (handball players, 18–30 yr) were recruited: 15 long-term users of OC (7.0 ± 0.6 yr) and 15 nonusers (>5 yr). Synchronized values of patellar tendon elongation (obtained by ultrasonography) and tendon force were sampled during ramped isometric knee extensor maximum voluntary contraction to estimate mechanical tendon properties. Furthermore, tendon cross-sectional area and length were measured from MRI images, and tendon biopsies were obtained for analysis of tendon fibril characteristics and collagen cross-linking. Overall, no difference in tendon biomechanical properties, tendon fibril characteristics, or collagen cross-linking was observed between the OC users and nonusers, or between the different phases of the menstrual cycle. In athletes, tendon cross-sectional area in the preferred jumping leg tended to be larger than that in the contralateral leg ( P = 0.09), and a greater absolute ( P = 0.01) and normalized tendon stiffness ( P = 0.02), as well as a lower strain ( P = 0.04), were observed in the jumping leg compared with the contralateral leg. The results indicate that long-term OC use or menstrual phases does not influence structure or mechanical properties of the patellar tendon in female team handball athletes.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Qianru Li ◽  
Qi Zhang ◽  
Yehua Cai ◽  
Yinghui Hua

Purpose. To evaluate differences of Achilles tendon (AT) hardness and morphology between asymptomatic tendons in patients with acute AT ruptures on the contralateral side and asymptomatic tendons in healthy people by using computer-assisted quantification on axial-strain sonoelastography (ASE). Methods. The study consisted of 33 asymptomatic tendons in 33 patients (study group) and 34 tendons in 19 healthy volunteers (control group). All the tendons were examined by both ASE and conventional ultrasound. Computer-assisted quantification on ASE was applied to extract hardness variables, including the mean (Hmean), 20th percentile (H20), median (H50) and skewness (Hsk) of the hardness within tendon, and the ratio of the mean hardness within tendon to that outside tendon (Hratio) and three morphological variables: the thickness (THK), cross-sectional area, and eccentricity (ECC) of tendons. Results. The Hmean, Hsk, H20, H50, and Hratio in the proximal third of the tendon body in study group were significantly smaller than those in control group (Hmean: 0.43±0.09 vs 0.50±0.07, p=0.001; Hsk: -0.53±0.51 vs -1.09±0.51, p<0.001; H20: 0.31±0.10 vs 0.40±0.10, p=0.001; H50: 0.45±0.10 vs 0.53±0.08, p<0.001; Hratio: 1.01±0.25 vs 1.20±0.23, p=0.003). The THK and cross-sectional area of tendons in the study group were larger than those in the control group (p<0.05). Conclusions. As a quantitative objective method, the computer-assisted ASE reveals that the asymptomatic ATs contralateral to acute rupture are softer than those of healthy control group at the proximal third and the asymptomatic tendons in people with rupture history are thicker, larger, and rounder than those of normal volunteers especially at the middle and distal thirds of AT body.


2021 ◽  
pp. 20210290
Author(s):  
Ankita Aggarwal ◽  
Chandan Jyoti Das ◽  
Neena Khanna ◽  
Raju Sharma ◽  
Deep Narayan Srivastava ◽  
...  

Objective: Early detection of peripheral neuropathy is extremely important as leprosy is one of the treatable causes of peripheral neuropathy. The study was undertaken to assess the role of diffusion tensor imaging (DTI) in ulnar neuropathy in leprosy patients. Methods: This was a case–control study including 38 patients (72 nerves) and 5 controls (10 nerves) done between January 2017 and June 2019. Skin biopsy proven cases of leprosy, having symptoms of ulnar neuropathy (proven on nerve conduction study) were included. MRI was performed on a 3 T MR system. Mean cross-sectional area, fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of ulnar nerve at cubital tunnel were calculated. Additional ancillary findings and appearance of base sequences were evaluated. Results: Ulnar nerve showed thickening with altered T2W signal in all the affected nerves, having an average cross-sectional area of 0.26 cm2. Low FA with mean of 0.397 ± 0.19 and high ADC with mean of 1.28 ± 0.427 x 10 −3 mm2/s of ulnar nerve in retrocondylar groove was obtained. In the control group, mean cross-sectional area was 0.71cm2 with mean FA and ADC of 0.53 ± 0.088 and 1.03 ± 0.24 x 10 −3 mm2/s respectively. Statistically no significant difference was seen in diseased and control group. Cut-off to detect neuropathy for FA and ADC is 0.4835 and 1.1020 × 10 −3 mm2/s respectively. Conclusion: DTI though is challenging in peripheral nerves, however, is proving to be a powerful complementary tool for assessment of peripheral neuropathy. Our study validates its utility in infective neuropathies. Advances in knowledge: 1. DTI is a potential complementary tool for detection of peripheral neuropathies and can be incorporated in standard MR neurography protocol. 2. In leprosy-related ulnar neuropathy, altered signal intensity with thickening or abscess of the nerve is appreciated along with locoregional nodes and secondary denervation changes along with reduction of FA and rise in ADC value. 3. Best cut-offs obtained in our study for FA and ADC are 0.4835 and 1.1020 × 10 −3 mm2/s respectively.


2019 ◽  
pp. 014556131987472
Author(s):  
Jie Cai ◽  
Logan Klein ◽  
Pinhong Wu ◽  
Azure Wilson ◽  
Xinlin Xu ◽  
...  

Objective: To investigate the value of diffusion tensor imaging (DTI) in the evaluation of vocal fold tissue microstructure after recurrent laryngeal nerve (RLN) injury. Methods: Six canines were divided into 2 groups: a unilateral vocal fold paralysis group (n = 4) and a control group (n = 2). The RLN was cut in the unilateral vocal fold paralysis group, and no intervention was applied in the control group. After 4 months, the canines’ larynges were removed and placed in a small animal magnetic resonance imaging (MRI) system (9.4T BioSpec MRI; Bruker, Germany). After scanning, the vocal folds were isolated, sectioned, and stained. The slides were then analyzed for the cross-sectional area and muscle fiber density through feature extraction technology. Pearson correlation analysis was performed on the DTI scan and histological section extraction results. Results: In the vocal fold muscle layer, the fractional anisotropy (FA) of the unilateral RLN injury group was higher than that of the control group, and the Tensor Trace was lower than that of the control group. This difference was statistically significant, P < .05. In the lamina propria, the FA of the unilateral RLN injury group was lower than that of the control group, P > .05, and the Tensor Trace was lower than that of the control group, P < .05. The muscle fiber cross-sectional area of the RLN injury group was significantly smaller than the control group with statistical significance, P < .05, and the density of muscle fibers was lower, P < .05. The correlation coefficient between FA and the cross-sectional area was −0.838, P = .002, and .726; P = .017 between Tensor Trace and the cross-sectional area. Conclusion: Diffusion tensor imaging is an effective method to assess the changes in the microstructure of atrophic vocal fold muscle tissue after RLN injury.


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