scholarly journals The value of the hedgehog signal in osteoblasts in fluoride-induced bone-tissue injury

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Chaonan Deng ◽  
Lin Xu ◽  
Ying Zhang ◽  
Lina Zhao ◽  
Yan Linghu ◽  
...  

Abstract Objective This study was designed to observe the expression of important hedgehog (Hh) signal factors in the bone tissue of rats with chronic fluorosis and cultured osteoblasts in order to investigate the role and significance of the Hh signal in fluoride-induced bone injury. Methods Healthy Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the fluorosis group (F Group), the fluoride + blocker group (F + Cycl group: rats were treated with fluoride + cyclopamine), and the fluoride + blocker control group (F + DMSO group). After 6 months of intervention, the urinary fluoride content of rats in each group was detected. The primary osteoblasts of rats were selected for cell experiment, and the experiment was carried out after the cells were passaged from the second to the fourth generation. Results The proliferation rate of primary rat osteoblasts presented time-affected and dose-affected relationships in a short time under treatment with a low dose of sodium fluoride (NaF), but the proliferation of osteoblasts was inhibited by long-term and high-dose NaF exposure. In the F group, the alkaline phosphatase (ALP) activity of osteoblasts increased gradually. The ALP activity was lower in the F + Cycl group than in the F group, and there was no significant difference between the F + DMSO group and F group. With the increase in fluoride exposure, the expression of Hh signal factors and osteogenic-related factor proteins increased gradually. The expressions of Indian hedgehog (Ihh), smoothened (Smo), Glioma-associated oncogene homolog (Gli) 2, and Runt-related transcription factor 2 (Runx2)in the F + Cycl group increased with the dose of fluoride but they were significantly inhibited compared with the F group. Compared with the control group, the content of urinary fluoride in the F group was significantly higher (P < 0.05), but there was no significant change in urinary fluoride content in the F + Cycl group and the F + DMSO group. Compared with the control group, the serum bone alkaline phosphatase (BALP) contents of rats in the other groups increased after 6 months’ intake of fluoride water (P < 0.05). After drug blocking, the serum BALP content in the F + Cycl group was lower than that in the F + DMSO group (P < 0.05). The BALP content in the F + DMSO group was similar to that in the F group: it did not decrease. The mRNA expressions of Ihh, Smo, Gli2, and Runx2 in bone tissue of the F group were significantly higher than those in the control group (P < 0.05). After cyclopamine blocking, the expressions decreased (P < 0.05), but the differences between the F + DMSO group and F group were not statistically significant. Conclusion Hh signal plays an important role in fluoride-induced bone injury. The effective inhibition of cyclopamine is expected to be a new target for the treatment of skeletal damage caused by fluorosis.

Author(s):  
Meilinah Hidayat ◽  
Sijani Prahastuti ◽  
Estherolita Dewi ◽  
Dewi Safitri ◽  
Siti Farah Rahmawati ◽  
...  

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.


2007 ◽  
Vol 7 (3) ◽  
pp. 212-217 ◽  
Author(s):  
Sabaheta Hasić ◽  
Radivoj Jadrić ◽  
Emina Kiseljaković ◽  
Zakira Mornjaković ◽  
Mira Winterhalter-Jadrić

In our investigation, we used short-time model of myocardial infarction of rats induced by high dose of isoproterenol (ISP). We investigated cardiac troponin T blood level (cTnT) and histological characteristics of rat myocardium. ISP, single, intraperitoneal dose 250 mg/kg was given to male, adult, Wistar rats (n=12). Rats were distributed depending on their body weight in subgroups: ISP I (BW 260-280g) and ISP II (BW 250-400g). Control group (n=9) was treated with intraperitoneal dose of 0,95% NaCl. Cardiac TnT was measured by electrochemiluminiscence (ECLA) sandwich immunoassay in rat serum 4 hours after ISP application. Rats’ hearts were dissected and examined by qualitative histological method (HE). Statistical significance was set at 0,05. There was significant difference in cTnT of ISP II (p=0,0001) vs. control and ISP I (p<0,05) vs. control. Significant difference was beetween ISP I and ISP II subgroups (p<0.001). The accent of histological changes of myocardium was on nuclei of cell. Cells showed acydophilic changes and nuclei disappearance as signs of coagulative necrosis development. Extensivity of histological changes were different beetween ISP I and ISP II subgroup. Used dose of ISP induced development of myocardial necrosis in rats. Suben-docardial portion of myocardium was more vulnerability than subepicardial portion. Rats of ISP II had more extensive histological changes than these in ISP I. Administered doses of ISP enabled cTnT utilization as a marker of myocardial necrosis.


2018 ◽  
Vol 52 (4) ◽  
pp. 185-191
Author(s):  
Tomomi Nobashi ◽  
Tsuneo Saga ◽  
Yuji Nakamoto ◽  
Yoichi Shimizu ◽  
Sho Koyasu ◽  
...  

AbstractObjective. This study investigated whether the metformin (Met)-induced enhanced intestinal uptake of 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) is reduced by loperamide, a long-acting anti-diarrheal agent. Methods. Mean18F-FDG uptake in the mouse small intestine and colon with Met exposure was compared with that in control mice. In the Met group, high-dose (1.0 mg/kg body weight) and low-dose (0.1 mg/kg body weight) loperamide were introduced, and18F-FDG uptake in the small intestine and colon was compared with that of control mice administered high-dose loperamide. The percent injected dose of18F-FDG per gram of tissue (%ID/g) in the extracted tissues was then determined. Results.18F-FDG uptake increased significantly in the small intestine (0.64±0.06 vs. 1.01±0.15, p=0.040) and, especially, the colon (0.46±0.13 vs. 2.16±0.51, p<0.001) after Met exposure. Neither high-dose nor low-dose loperamide significantly reduced18F-FDG uptake in the small intestine (0.82±0.31 vs. 0.84±0.22, p=0.93 and 0.78±0.25 vs. 0.70±0.15, p=0.13, respectively) or colon (2.13±0.41 vs. 1.67±0.55, p=0.063 and 1.77±0.39 vs. 1.80±0.25, p=0.56, respectively). The colonic %ID/g was significantly higher in Met groups irrespective of loperamide introduction than in control group, whereas the significant difference in the small intestine was observed only between Met and control groups. Conclusion. Metformin increased18F-FDG uptake in intestines especially in colon. Loperamide administration partially, but not sufficiently, suppresses the Met-induced increased colonic uptake of18F-FDG.


2018 ◽  
Vol 7 (4.26) ◽  
pp. 136
Author(s):  
Irfiansyah Irwadi ◽  
Hayuris Kinandita ◽  
Jamaluddin Mahmud ◽  
Lilik Herawati

Aim: Antioxidants, such as vitamin C and vitamin E, is widely used as supplements. The aim of this study is to analyze the profile of blood glucose, serum insulin, and  HOMA in active teenagers after vitamin C and vitamin E supplementation.Methods: Subjects (14-16 y.o) consisted of 12 boys and 5 girls, divided into 3 groups: control (4 boys, 2 girls), ‘moderate dose’ of vitamin C and vitamin E combination group (5 boys, 1 girls), and ‘high dose’ of vitamin C and vitamin E combination group (3 boys, 2 girls). The treatment was given for 5 days. Vitamin C and vitamin E for ‘moderate dose’ was 500mg;  200IU, and for ‘high dose’ was 1000mg; 400IU. Fasting Blood Glucose (FGB) and 1 hour BG (1hr_BG), fasting serum insulin (FSI) and 1 hour SI (1hr_SI) was collected after treatment. We also calculated the HOMA-IR and HOMA-β.Result: There was no significant difference on FBG, 1hr_BG, FSI, 1hr_SI, HOMA-IR, and HOMA-β (p≥ 0.05). However, mean FBG and 1hr_BG tended to be higher on the treatment groups. The control group had the lowest HOMA-IR and the highest HOMA-β.Conclusions: We suggest that the supplementation of vitamin C and vitamin E in active teenagers is not essential on glucose homeostasis.  


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1251-1251
Author(s):  
Shu-Quan Ji ◽  
Hui-Ren Chen ◽  
Heng-Xiang Wang ◽  
Hong-Min Yan ◽  
Mei Xue ◽  
...  

Abstract Between February 1999 and March 2004, eighty-seven patients with high risk leukemia, age 3–50 (median 19 year), who needed urgent transplant but no HLA-matched or single HLA-antigen mismatched donors available, received unmanipulated HLA haploidentical BMT. The 87 patients were classified as follows AML 27 (CR1 in 7, CR2 in 15 and 5 in relapse), All 38 (CR1 in 4, CR2 in 30 and 4 in relapse) , CML 22 ( 4 in CP, 12 in AP and 6 in BP). All donors were HLA-haploidentical relatives who had at least two major histocompatibility complex antigen mismatched with the recipients. 87 patients underwent haplo-BMT with G-CSF primed BM as stem cells. All patients received a same conditioning regimen including high dose Ara-C, Cyclophosphamide, antithymocyte globulin and total body irradiation to provide both immunosuppression and myeloablation. GVHD prophylaxis consisted of anti-thymocyte globulin, cyclosporin A, methotrexate and mycofenolate mofitel. 72 patients underwent the transplants with the addition of CD25 mAb (Basiliximab Novartis) for GVHD prophylaxis designated as CD25 mAb group. Basiliximab 20mg each by 30min intravenous infusion on 2 hours before transplantion and day 4 after transplantaion. The other 15 patients without Basiliximab for GVHD prophylaxis were as the control group. The two group of patients were comparable in disease status, HLA-disparity and median age of patients. Immunophenotyping, limited dilution assay and colony forming assays were used to measure the effect of Basiliximab on the subsets of lymphocytes, cytotoxic T lymphocyte precursors (CTLp) and hematopoietic cells. All donors were primed with G-CSF at 3-5ug/kg/d for 7 days and the marrow cells were harvested on the eighth day. G-CSF donor priming significantly increased CD34+ and colony forming progenitors in the marrow grafts. More importantly, it significantly reduced lymphocytes and reversed CD4+/CD8+ lymphocyte ratio in the grafts. Both of group who were treated with and without Basiliximab had similar marrow graft contents. All patients established trilineage engraftments.The median time to achieve an absolute neutrophil count 0.5x109/L was 19 days (range, 13 to 24 days). The median time to achieve platelets above 20x109/L was 22 days (range, 16 to 32 days). Between the two groups were no differences in engraftment. Incidence of grades II–IV acute GVHD were 13.9% with GVHD-related deaths 6.9% in Basiliximab group and 33.3% with 20% GVHD-related deaths in control group. There were a significant difference between the anti-CD25 mAb treated Vs non-treated group.Forty-nine patients who survived over 12 months were eligible for the evaluation of cGVHD. 12 patients developed extensive cGVHD, one in control group and eleven in Basiliximab group. 49 were alive in CR during a median follow-up of 30 months (range3–64 months), 42 in Basiliximab group and 7 in control group. Basiliximab significantly decreased alloreactive CTLp by 10–100 fold in limiting dilution assays. It had no effect on hematopoietic stem and progenitor cells as determined by in vitro colony-forming assays.The addition of basiliximab as aGVHD prophylaxis effectively reduced severe lethal aGVHD in haplo-BMT. It is possible to selectively eliminate or reduce the number of alloreactive T cells with anti CD25 antibody, which results in prevention of or a reduction in the severity of GVHD.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4226-4226
Author(s):  
Mohsen Saleh Elalfy ◽  
Iman Ahmed Ragab ◽  
Enas Ahmed Azab ◽  
Shaimaa Nasr ◽  
Marwa Abdel Maguid

Abstract Abstract 4226 Patients with childhood ALL achieve long-term disease-free survival, making reducing complications of therapy of major concerns. The aim of this study was to assess the prevalence and degree of neurocognitive dysfunction in survivors of childhood ALL treated with different protocols and the effect of time since end of chemotherapy. Patients and methods: A cross-sectional study including 60 ALL survivors aged 5–16 years at enrollment; 2–9 years at diagnosis, CNS1, treated through 1998–2008 and regularly followed up in childhood cancer survivors clinic;. They were compared to 20 healthy age and sex matched controls. Grade of school, scholastic achievement in the previous year were reported followed by revision of hospital records including type and risk of ALL, protocol of treatment, number, type and dose of intrathecal chemotherapy, number and doses of high dose I.V methotrexate, data of cranial radiotherapy. Three different protocols were applied to these patients according to the time of diagnosis, patients diagnosed between January 1998 to December 2000 were treated with Modified BFM 83. Those diagnosed between January 2001 to June2004 were treated with BFM 90 protocol, and those diagnosed From July 2004 to June 2008 were treated with CCG 1991 for standard risk and CCG 1961 for high risk patients.Neurocognitive functions were tested using Wechsler Intelligence Scale for Children,Benton visual retention (BVR) test and Trail making test (part A and B were done. MRI Brain was performed to the patients and control group using diffusion weighed images and diffusion tensor magnetic resonance imaging (DTI). Results: Survivors treated with CCG protocol showed a significant decrease in all cognitive tests results compared to control (p<0.05). Survivors treated with BFM 90 protocol had a significant lower total IQ, verbal IQ, TMT-partA, compared to both control and survivors treated with Modified BFM 83, and a significant decrease in performance IQ, BVRT and TMT-partB compared to control only. No significant difference between results of cognitive tests in survivors treated with Modified BFM 83 and control group. Both left and right frontal cortex apparent diffusion coefficient (ADC) was significantly higher in CCG(.88±.060.91±.028) treated group compared to control(.695±.0018.684±.0018), BFM 90(.79±.071.76±.048) and modified BFM 83(.76±.030.83±.023×10&minus;3mm2/s) groups (p<0.05) yet a significant decrease in FA of right frontal cortex only in CCG (.250±.039)treated group compared to control(.684±.0018), BFM 90(.450±.042) and Modified BFM 83(.41±.028) groups(p<0.05). FA of right frontal, was significantly lower in BFM 90 and Modified BFM 83 treated group compared to control group. No significant correlation was found between cognitive tests results with age at diagnosis, time since the end of therapy, total number of intrathecal injections, age at radiotherapy treatment, dose and time of radiotherapy. Cognitive tests didn’t differ between survivors treated with triple intrathecal therapy(ITTT) compared to those treated with intrathecal methotrexate, yet significant decrease in FA of right hippocampus in survivors who received ITTT compared to survivors treated with intrathecal monotherapy, Conclusion: Neurocognitive dysfunction was a common sequelae of childhood ALL treatment. It was more related to protocol of therapy rather than the duration of follow-up since end of chemotherapy. Frontal lobe FA may be a clinically useful biomarker for the assessment of neurotoxicity in post-treatment childhood ALL survivors. Disclosures: No relevant conflicts of interest to declare.


2014 ◽  
Vol 42 (03) ◽  
pp. 605-618 ◽  
Author(s):  
Moo-Yong Rhee ◽  
Belong Cho ◽  
Kwang-Il Kim ◽  
Joohee Kim ◽  
Mi Kyung Kim ◽  
...  

We investigated the effect of Panax ginseng extract, which is rich in the ginsenoside protopanaxatriol (Ginseol K-g1), on blood pressure (BP). Adults over 20 years old with a systolic BP (SBP) between 120 and 159 mm Hg or a diastolic BP (DBP) between 80 and 99 mm Hg were included. At the end of an initial 2-week washout period, the patients were divided into three groups: the control group (placebo), the low-dose Ginseol K-g1 group (100 mg), and the high-dose Ginseol K-g1 (300 mg) group. The primary end point was the difference in seated SBP (seSBP) and seated DBP (seDBP) changes between the placebo and Ginseol K-g1 groups after 8 weeks of treatment. A total of 90 subjects participated in the study (mean age; 55.2 ± 11.8 years, 43 males). At week 8, levels of seSBP and seDBP were significantly decreased from baseline in the high-dose Ginseol K-g1 group (-3.1 mm Hg and -2.3 mm Hg, respectively, p < 0.05). In contrast, there was no significant decrease in seSBP or seDBP in the control or low-dose Ginseol K-g1 groups. No significant difference of seSBP and seDBP was identified among the three treatment groups at week 8. In patients who had a seSBP ≥ 130 mm Hg or an seDBP ≥ 85 mm Hg, the high dose of Ginseol K-g1 decreased the BP compared with the control group at week 4; however, there was no significant difference at week 8. The proportions of patients who experienced adverse events were comparable among the treatment groups. In conclusion, Ginseol K-g1 has a favorable effect on BP after 4 weeks of treatment, especially at a high dose. However, the effect is not maintained over 8 weeks. (Clinical trial registration information is available at http://www.clinicaltrials.gov , identifier: NCT01483430.)


2020 ◽  
Vol 17 (35) ◽  
pp. 65-72
Author(s):  
Noor AL-Huda Salah AL-ZUHAIRY ◽  
Zainab Abdul Jabbar Ridha AL-ALI

Beta-thalassemia is a heterogeneous group of hereditary blood disorders characterized by defects in the synthesis of the β- chains of hemoglobin, resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. This study aims to assess the serum PTH, vitamin D, calcium, phosphorus, alkaline phosphatase, and magnesium levels in β-thalassemia major patients. A total of 50 (30 male and 20 female) patients with β- thalassemia major with ages range 11- 16 years and an equal number of sex-matched healthy adolescents as a control group were included in this study. A total of 52% of patients were lived in an urban area, and there was no significant difference between patients and the control group regarding residency. Male patients showed low statistically significant (P 0.05) mean serum PTH, vitamin D, and calcium levels, but mean serum phosphorus and alkaline phosphatase levels were significantly higher (P 0.05) as compared to the male control group. However, female patients had low, but without statistical significant (P>0.05) mean serum PTH level, whereas vitamin D and calcium levels were highly significant (P 0.05) reduced. The phosphorus and ALP levels were highly significantly (P 0.05) increased as compared to female controls. Regarding β- thalassemia major group, the current study showed male patients had non-significant (P 0.05) higher levels of PTH, calcium, phosphorus, and ALP. In contrast, vitamin D level was non-significantly (P 0.05) low in male patients as compared to female patients. Mean serum level of PTH had a negative correlation with phosphorus, but it had a positive association with vitamin D, calcium, ALP, and magnesium. In conclusion, this study demonstrated that β-thalassemia major patients have a markedly deranged biochemical metabolic bone profile. Regular monitoring of PTH and biochemical mineral profile is also recommended.


2019 ◽  
Vol 52 (1) ◽  
pp. 13
Author(s):  
Amiyatun Naini ◽  
I Ketut Sudiana ◽  
Mohammad Rubianto ◽  
Utari Kresnoadi ◽  
Faurier Dzar Eljabbar Latief

Background: Damage to bone tissue resulting from tooth extraction will cause alveolar bone resorption. Therefore, a material for preserving alveolar sockets capable of maintaining bone is required. Hydroxyapatite Gypsum Puger (HAGP) is a bio-ceramic material that can be used as an alternative material for alveolar socket preservation. The porous and rough surface of HAGP renders it a good medium for osteoblast cells to penetrate and attach themselves to. In general, bone mass is regulated through a remodeling process consisting of two phases, namely; bone formation by osteoblasts and bone resorption by osteoclasts. Purpose: This research aims to identify the effects of HAGP scaffold application on the number of osteoblasts and osteoclasts, as well as on the width of trabecular bone area in the alveolar sockets of rats. Methods: This research used Posttest Only Control Group Design. There were three research groups, namely: a group with 2.5% HAGP scaffold, a group with 5% HAGP scaffold and a group with 10% HAGP scaffold. The number of samples in each group was six. HAGP scaffold at concentrations of 2.5%, 5% and 10% was then mixed with PEG (Polyethylene Glycol). The Wistar rats were anesthetized intra-muscularly with 100 mg/ml of ketamine and 20 mg/ml of xylazine base at a ratio of 1:1 with a dose of 0.08-0.2 ml/kgBB. Extraction of the left mandibular incisor was performed before 0.1 ml preservation of HAGP scaffold + PEG material was introduced into the extraction sockets and suturing was performed. 7 days after preparation of the rat bone tissue, an Hematoxilin Eosin staining process was conducted in order that observation under a microscope could be performed. Results: There were significant differences in both the number of osteoclasts and osteoblasts between the 2.5% HAGP group, the 5% HAGP group and the 10% HAGP group (p = 0.000). Similarly, significant differences in the width of the trabecular bone area existed between the 5% HAGP group and the 10% HAGP group, as well as between the 2.5% HAGP group and the 10% HAGP group (p=0.000). In contrast, there was no significant difference in the width of the trabecular bone area between the 2.5% HAGP group and the 5% HAGP group. Conclusion: The application of HAGP scaffold can reduce osteoclasts, increase osteoblasts and extend the trabecular area in the alveolar bone sockets of rats.


2020 ◽  
Vol 11 (2) ◽  
pp. 289-293
Author(s):  
M. A. Rybalka ◽  
L. M. Stepchenko ◽  
O. O. Shuleshko ◽  
L. V. Zhorina

Humic acids are characterized by chelating properties due to which they are able to influence the mineral metabolism in animals. Rabbits have species-specific characteristics of mineral metabolism, which distinguishes them from most species of mammals. For the experiment, 16 rabbits of 45-day-old of Hyplus breed were divided into the experimental and control group of 8 rabbits in each. The animals were 15 days in the preparatory period. The rabbits of the experimental group received humic acid additive individually with water in the amount of 5 mg/kg, the rabbits of the control group received pure water in the same amount. The ability of humic acid additive to increase the content of calcium, ionized calcium, iron, to correct the content of copper and zinc, and also to increase the activity of alkaline phosphatase in the blood serum of rabbits of the experimental group has been proved. We observed the early effect of the humic acid additive on increasing the content of iron and calcium ionized and a later effect on the activity of alkaline phosphatase and an increase in the content of copper in the blood serum. The influence of humic acid additive on the distribution of calcium, phosphorus, manganese, copper and zinc in bone tissue is determined. According to a histological study, there was a significant increase in the number of layers of osteons and osteoblasts in the bone tissue of the femur, an increase in the number of osteons and osteoblasts in the bone tissue of the sternum and an increase in the number of columns of chondrocytes and an increase in the number of chondrocytes in the column in the cartilaginous tissue of the sternum. The results of a histological study of bone tissue, together with an increase in structural macroelements in it and redistribution of osteotropic trace elements in the blood and bone tissue suggest the possibility of using a humic acid additive to intensify the growth and mineralization of bone tissue, which can improve the state of bone tissue of rabbits in the postnatal period ontogenesis.


Sign in / Sign up

Export Citation Format

Share Document