• Title/Summary/Keyword: Systemic Model

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The Anti-tumor Effect of Polysaccharide from the Leaves of Panax Ginseng C.A. Meyer(MB40) in a Murine Squamous Cell Carcinoma Model (편평세포암 동물 모델에서 고려인삼잎-다당체(MB40)의 항암치료효과)

  • Joo, Eun-Jung;Choi, Jun;Chung, Eun-Jae;Hong, Seok-Jin;Cho, Jae-Gu;Baek, Seung-Kuk;Woo, Jeong-Soo;Jung, Kwang-Yoon;Kwon, Soon-Young
    • Korean Journal of Head & Neck Oncology
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    • v.25 no.1
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    • pp.3-7
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    • 2009
  • Background and Objectives : Panax ginseng C.A. Meyer is a medical plant that has been widely utilized as a tonic and nutritional agent since ancient times in Korea. Ginseng has anti-metastatic property of cancer and immunomodulating activity. The novel acidic polysaccharide compound(MB40) was isolated from the leaves of Panax ginseng C.A. Meyer. To determine immunomodulating activities of MB40, we evaluate anti-cancer and anti-metastatic effects of MB40 in tumor bearing immune competent mice. Material and Methods : C3H mice were divided into three equal groups(Cisplatin treatment group, MB40 treat-ment group, Cisplatin and MB40 treatment group) and were transplanted SCC(Squamous Cell Carcinoma) cells(2${\times}$106) to the lateral side of abdomen. From day 4 after transplantation, MB40 was administrated at dose of 10mg/kg, respectively, every other day by intratumoral injection. Cisplatin was systemically administrated at doses of 1mg/kg, respectively, every week by intraperitoneal injection. Results : 5 days after administration, tumors can be palpated in every mice group. After 13 days of administration, the mice group to which MB40 were administrated exhibited reduction in tumor size respectively, compared to cisplatin group. Overall status of mice such as body weight and activity were superior in MB40 group than cisplatin group. Conclusion : The result of this study indicates MB40 may have significant therapeutic effect and decreases complications induced by systemic chemotheraphy. MB40 may be developed as a novel and potent immunotropics to improve the cell immune system and anti-cancer drug for the treatment of cancer patients in head and neck squamous cell carcinoma.

External validation of IBTR! 2.0 nomogram for prediction of ipsilateral breast tumor recurrence

  • Lee, Byung Min;Chang, Jee Suk;Cho, Young Up;Park, Seho;Park, Hyung Seok;Kim, Jee Ye;Sohn, Joo Hyuk;Kim, Gun Min;Koo, Ja Seung;Keum, Ki Chang;Suh, Chang-Ok;Kim, Yong Bae
    • Radiation Oncology Journal
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    • v.36 no.2
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    • pp.139-146
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    • 2018
  • Purpose: IBTR! 2.0 nomogram is web-based nomogram that predicts ipsilateral breast tumor recurrence (IBTR). We aimed to validate the IBTR! 2.0 using an external data set. Materials and Methods: The cohort consisted of 2,206 patients, who received breast conserving surgery and radiation therapy from 1992 to 2012 at our institution, where wide surgical excision is been routinely performed. Discrimination and calibration were used for assessing model performance. Patients with predicted 10-year IBTR risk based on an IBTR! 2.0 nomogram score of <3%, 3%-5%, 5%-10%, and >10% were assigned to groups 1, 2, 3, and 4, respectively. We also plotted calibration values to observe the actual IBTR rate against the nomogram-derived 10-year IBTR probabilities. Results: The median follow-up period was 73 months (range, 6 to 277 months). The area under the receiver operating characteristic curve was 0.607, showing poor accordance between the estimated and observed recurrence rate. Calibration plot confirmed that the IBTR! 2.0 nomogram predicted the 10-year IBTR risk higher than the observed IBTR rates in all groups. High discrepancies between nomogram IBTR predictions and observed IBTR rates were observed in overall risk groups. Compared with the original development dataset, our patients had fewer high grade tumors, less margin positivity, and less lymphovascular invasion, and more use of modern systemic therapies. Conclusions: IBTR! 2.0 nomogram seems to have the moderate discriminative ability with a tendency to over-estimating risk rate. Continued efforts are needed to ensure external applicability of published nomograms by validating the program using an external patient population.

Antiinflammatory and Antiallergic Activity of Fermented Turmeric by Lactobacillus johnsonii IDCC 9203 (Lactobacillus johnsonii IDCC 9203으로 발효한 울금의 소염 및 항알레르기 효과)

  • Kim, Seong-Beom;Kang, Byung-Hwa;Kwon, Hyuk-Sang;Kang, Jae-Hoon
    • Microbiology and Biotechnology Letters
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    • v.39 no.3
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    • pp.266-273
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    • 2011
  • Although turmeric has numerous pharmacological effects, the poor water-solubility of curcuminoids, active components of turmeric, restricts their systemic availability in orally administered formulations and limits their therapeutic potential. In this study we attempted turmeric fermentation using several probiotic bacteria to improve its solubility, and also investigated the effects of turmeric and fermented turmeric on anti-inflammatory activity. Fermented turmeric, by L. johnsonii IDCC 9203, more strongly inhibited LPS-induced expression of the pro-inflammatory cytokines than non-fermented turmeric and fermented turmeric by other probiotic strains. We used an NC/Nga mouse model for mite antigen-induced atopic dermatitis to examine the efficacy of the fermented turmeric. Fermented turmeric-fed mice exhibited a significantly reduced serum IgE level and mitigated acute inflammation. When the fermented turmeric was pre-treated by oral administration, it had more preventive activity against acute anaphylactic reaction than the non-fermented group. In addition, we observed that fermentation of turmeric leads to increased water-solubility of curcumin and a change in the active components ratios for bisdemethoxycurcumin, demethoxycrucumin and curcumin. Taken together, these results strongly suggest that fermented turmeric by L. johnsonii IDCC 9203 could be used as a functional food ingredient for improving treatments for atopic dermatitis.

EFFECTS OF LOCAL IRRIGATION AND/OR INTRAVENOUS ADMINISTRATION OF ARGATROBAN ON THROMBOSIS IN MICROVASCULAR ANASTOMOSES OF FEMORAL VEIN OF RABBIT (가토대퇴정맥에서 미세혈관문합시 Argatroban의 국소세척 및 전신투여가 혈전형성에 미치는 영향)

  • Kook, Min-Suk;Park, Hong-Ju;Oh, Hee-Kyun
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.31 no.4
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    • pp.300-305
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    • 2005
  • Purpose: For the reconstruction of maxillofacial defect created by trauma, infection, or tumor etc, the role of microvascular anastomosis or vessel graft has been increased. Many methods has been tried to increase the success rate of microvascular anastomosis. Various anticoagulants and thrombolytic agents have been used to reduce the failure rate of microvascular anastomosis and avoid re-operation. Many drugs, however, have been used in the limited cases because most of these drugs may cause complications, such as allergy, fever or systemic bleeding. This study was performed to evaluate the influence of the Argatroban on patency and thrombosis in microvascular anastomosis when it is used for local irrigation or general administration. Materials & methods: Eight mature rabbits, weighing 2kg, were used. After exposing both femoral veins, the artificial thrombotic model was made by crushing injury using a smooth needle holder, and the transverse incision were made on femoral vein. The animals were divided into 4 groups according to Argatroban administration methods; control group (n=4), topical irrigation of lumen with saline solution; experimental group 1 (n=4), topical irrigation of lumen with Argatroban saline solution; experimental group 2 (n=4), topical irrigation of lumen with heparin followed by intravenous injection of Argatroban; experimental group 3 (n=4), topical irrigation of lumen with Argatroban followed by IV of Argatroban. Microvascular anastomosis was done with 10-0 Ethilon. The patency was evaluated by empty-and-refill test 30 minutes and 3 days after microanastomosis. The thrombus formation was examined 3 days after microanastomosis by surgical microscope. The histologic findings were also examined. Results: 1. Thirty minutes after microvascular anastomosis, the patency of all experimental groups was better than that of control group, but there was no significant difference among groups. 2. Three days after microvascular anastomosis, the patency of all experimental groups was more improved than that of control group (p<0.05). There was no significant difference among experimental groups. 3. Three days after microvascular anastomosis, the amount of thrombus in all experimental groups was less than that of control group (p<0.05). There was no significant difference among experimental groups. 4. Histologically, a lot of luminal thrombus was observed around sutured area in control group. Few luminal thrombus was observed in all experimental groups. The necrotic changes were observed on the sutured vein wall in all specimens. Conclusion: These results indicate that topical irrigation and/or intravenous administration of Argatroban is effective in improving patency and preventing thrombus formation after microvascular anastomosis.

Effects of Herbal medicine on Physiological Responses in Ovariectomized Rats and SAM P6 Mice (한약이 난소제거 흰쥐와 SAM P6 생쥐의 생리활성에 미치는 영향)

  • Kim, Chung-Sook;Kim, Jin-Sook;Kim, Yun-Tai;Lee, Je-Hyun
    • YAKHAK HOEJI
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    • v.42 no.4
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    • pp.370-381
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    • 1998
  • The effect of herbal medicine on osteoporosis was studied using ovariectomized rats as an animal model of Type I osteoporosis and SAM P6 mice as that of Type II. Each traditiona l boiling water extract of Achyranthis Radix, Psoraleae Radix, Rehmanniae Radix Preparat, Corni Fructus and Mycelia of Ganoderma, and systemic water fraction of Astragali Radix was given 5g(dried herbal weight)/kg/day p.o. for 30 days in each group of ovariectomized rats, SAM R1 and SAM P6. The extract of Cervi parvum Cornu was given for 14 days only. One ml of blood was taken by tail vein at day 0, 7, 14, 21 and 30 days after administration of the extract. Plasma levels of alkaline phosphatase, calcium, creatinine,inorganic phosphate, blood urea nitrogen, cortisol, total $T_3\;and\;total\;T_4$ were measured. In ovariectomized rats, administration of Achyranthis Radix or Corni Fructus decreased in alkaline phosphatase and that of Achyranthis Radix or Psoraleae Radix decreased in calcium comparing to the control (p<0.05). The administration of Psoralese Radix decreased in calcium and increased in urea comparing to day o(P<0.05)(Table I). There were not much changes in plasma calcium, inorganic phosphate, and alkaline phosphatase concentrations after uptake of these herbal medicine used in SAM P6(Table III). However, administration of Astragali Radix altered plasma inorganic phosphate and creatinine levels in SAM R1(p<0.01)(Table UU). The administration of Corni Fructus or Psoralease Radix induced the changes in plasma concentrations of cortisol, total $T_3$ and total $T_4$ in Type I(p<0.05) (Table IV). The uptake of Cervi parvum Cornu increased in total $T_3$ concentration and that of Mycelia of Ganodtragali Radix in SAM P6. However, the uptake of Mycelia of Ganoderma induced changes in cortisol and $T_4$ concentrations in SAM R1(p<0.05). Thus, there were significant differences in responses of herbal medicine in different types of osteoporosis.

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Ginsenoside Re Enriched Fraction (GS-F3K1) from Ginseng Berries Ameliorates Ethanol-Induced Erectile Dysfunction via Nitric Oxide-cGMP Pathway

  • Pyo, Mi Kyung;Park, Kwang-Hyun;Oh, Myeong Hwan;Lee, Hwan;Park, Young Sik;Kim, Na Young;Park, So Hee;Song, Ji Hye;Park, Jong Dae;Jung, Se-Hee;Lee, Bong-Gun;Won, Beom Young;Shin, Ki Young;Lee, Hyung Gun
    • Natural Product Sciences
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    • v.22 no.1
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    • pp.46-52
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    • 2016
  • Erectile dysfunction (ED) is a highly prevalent disorder that affects millions of men and considered to be an early symptom of atherosclerosis and a precursor of various systemic vascular disorders. The aim of the present study was to prepare ginsenoside Re enriched fraction (GS-F3K1, ginsenoside Re 10%, w/w) from ginseng berries flesh and to investigate the enhanced activities of GS-F3K1 on alcohol-induced ED. GS-F3K1 was prepared by the continuous liquid and solid separating centrifugation and circulatory ultrafiltration from ginseng berries flesh. GS-F3K1 was administered for 5 weeks in ethanol-induced ED rat by oral administration of 20% ethanol. To investigate the effects of GS-F3K1 on ED model, the levels of nitrite expression, cyclic guanosine monophosphate (cGMP) and erectile response of the penile corpus cavernosum of rat were measured. The erectile response of the corpus cavernosum was restored after GS-F3K1 administration, to a level similar to the normal group. The level of nitrite and cGMP expression in the corpus cavernosum of GS-F3K1-administered male rats was increased significantly compared to positive control group. GS-F3K1 from ginseng berries should effectively restore ethanol-induced ED in male rats and could be developed as a new functional food for the elderly men.

Comparative evaluation to select optimal adjuvant of novel type Salmonella Typhimurium inactivated bacteria for protecting Salmonella infections in a murine model (마우스에서 살모넬라 감염증 예방을 위한 신개념 Salmonella Typhimurium 불활화 사균체에 최적 adjuvant 선택을 위한 효능 비교 시험)

  • Moon, Ja-Young;Ochirkhuyag, Enkhsaikhan;Kim, Won-Kyong;Lee, Jun-Woo;Jo, Young-Gyu;Kwak, Kil Han;Park, Byung Yong;Hur, Jin
    • Korean Journal of Veterinary Service
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    • v.43 no.2
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    • pp.89-97
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    • 2020
  • This study was carried out to examine a novel inactivated Salmonella Typhimurium (S. Typhimurium) vaccine candidate for protection of mice against salmonellosis by immunization of BALB/c mice using various type adjuvant. The novel type-inactivated vaccine candidate was constructed by adding Chlorhexidine digluconate solution. BALB/c mice were divided into 6 groups of 15 mice apiece. The mice were intramuscularly (IM) primed at 6 weeks of age and were IM boosted 8 weeks of age. Groups A and B mice were injected with sterile phosphate-buffered saline as controls; group C mice were inoculated with 5×108 cells/100 µL of formalin-inactivated S. Typhimurium cells and adjuvant ISA70; groups D~F mice were immunized with 5×108 cells/100 µL of the inactivated vaccine candidate and adjuvant ISA70, adjuvant IMS1313 and adjuvant IMS1313 containing 30 ㎍/mL of GI24, respectively. All mice (except group A mice) were orally challenged with a virulent S. Typhimurium strain at 10 weeks of age. Mice from groups C-F had significantly increased IgG levels compared to control groups (A-B) mice. The levels of splenocyte IFN-γ and IL-4 in mice of all groups were measured by ELISA, resulting in increased immunity in group F mice compared to those of groups A-E mice. These data suggested that systemic and cell-mediated immune responses were highly induced by IM immunization with the vaccine candidate and adjuvant IMS1313 containing GI24. Furthermore, clinical signs such as death were observed in only 20% of group F mice after virulent Salmonella strain challenge, however, groups B and C (100%), and groups D and E (60%) mice died. This data suggested that mice immunized by intramuscular prime and booster with this vaccine candidate and adjuvant IMS1313 containing GI24 effectively protected mice from salmonellosis.

Effects of Geiji-Bokryung-Hwan on eNOS, nNOS, Caveolin-1 and bFGF Protein Expressions and the Endothelial Cells of the Corpus Cavernosum in Hypercholesterolemic Rat

  • Kim Jae-Woo;Son Soo-Gon;Sa Eun-Ho;Kim Cherl-Ho;Park Won-Hwan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.1
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    • pp.174-180
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    • 2006
  • We examine the effect of Geiji-Bokryung-Hwan(GBH) on erectile function in a rat model of hypercholesterolemic erectile dysfunction. GBH, a drug preparation consisting of five herbs of Cinnamomi Ramulus (Geiji), Poria Cocos (Bokryun), Mountan Cortex Radicis (Mokdanpi), Paeoniae Radix (Jakyak), and Persicae Semen (Doin) is a traditional Korean herbal medicine that is widely used in the treatment of atherosclerosis-related disorders. In this study, 3-month-old Sprague-Dawley rats were used. The 6 rats control animals were fed a normal diet and the other 18 rats were fed 1% cholesterol diet for 3 months. After 1 months, GBH was added to the drinking water of the treatment group of 12 rats but not the cholesterol only group of 6 rats. Of the 12 rats 6 received 30 mg/kg per day (group 1) and 6 received 60 mg/kg per day (group 2) of GBH. At 3 months erectile function was evaluated with cavernous nerve electrostimulation in all animals. Penile tissues were collected for electron microscopy, and to perform Western blot for endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), basic fibroblast growth factor (bFGF) and caveolin-1. Systemic arterial pressure was not significantly different between the animals that were fed the 1% cholesterol diet and the controls. Conversely erectile function was not impaired in the herbal medicine treated rats. Electron microscopy showed many caveolae with fingerlike processes in the cavernous smooth muscle and endothelial cell membranes in control and treated rats but not in the cholesterol only group of rats. Western blot showed differences among groups in protein expression for eNOS, nNOS, caveolin-1 and bFGF protein expression in penile tissue. Increased eNOS and nNOS protein expressions dy high cholesterol diet were significantly decreased in group 1 and group 2. Interestingly, caveolin-1 and bFGF protein expression was significantly higher in groups 1 and 2 than in the cholesterol only and control groups.

Gender-independent efficacy of mesenchymal stem cell therapy in sex hormone-deficient bone loss via immunosuppression and resident stem cell recovery

  • Sui, Bing-Dong;Chen, Ji;Zhang, Xin-Yi;He, Tao;Zhao, Pan;Zheng, Chen-Xi;Li, Meng;Hu, Cheng-Hu;Jin, Yan
    • Experimental and Molecular Medicine
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    • v.50 no.12
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    • pp.12.1-12.14
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    • 2018
  • Osteoporosis develops with high prevalence in both postmenopausal women and hypogonadal men. Osteoporosis results in significant morbidity, but no cure has been established. Mesenchymal stem cells (MSCs) critically contribute to bone homeostasis and possess potent immunomodulatory/anti-inflammatory capability. Here, we investigated the therapeutic efficacy of using an infusion of MSCs to treat sex hormone-deficient bone loss and its underlying mechanisms. In particular, we compared the impacts of MSC cytotherapy in the two genders with the aim of examining potential gender differences. Using the gonadectomy (GNX) model, we confirmed that the osteoporotic phenotypes were substantially consistent between female and male mice. Importantly, systemic MSC transplantation (MSCT) not only rescued trabecular bone loss in GNX mice but also restored cortical bone mass and bone quality. Unexpectedly, no differences were detected between the genders. Furthermore, MSCT demonstrated an equal efficiency in rectifying the bone remodeling balance in both genders of GNX animals, as proven by the comparable recovery of bone formation and parallel normalization of bone resorption. Mechanistically, using green fluorescent protein (GFP)-based cell-tracing, we demonstrated rapid engraftment but poor inhabitation of donor MSCs in the GNX recipient bone marrow of each gender. Alternatively, MSCT uniformly reduced the $CD3^+T$-cell population and suppressed the serum levels of inflammatory cytokines in reversing female and male GNX osteoporosis, which was attributed to the ability of the MSC to induce T-cell apoptosis. Immunosuppression in the microenvironment eventually led to functional recovery of endogenous MSCs, which resulted in restored osteogenesis and normalized behavior to modulate osteoclastogenesis. Collectively, these data revealed recipient sexually monomorphic responses to MSC therapy in gonadal steroid deficiency-induced osteoporosis via immunosuppression/anti-inflammation and resident stem cell recovery.

Effects of ibuprofen-loaded TiO2 nanotube dental implants in alloxan-induced diabetic rabbits

  • Kim, Young-Gyo;Kim, Wan-Tae;Jung, Bo Hyun;Yoo, Ki-Yeon;Um, Heung-Sik;Chang, Beom-Seok;Lee, Jae-Kwan;Choi, Won-Youl
    • Journal of Periodontal and Implant Science
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    • v.51 no.5
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    • pp.352-363
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    • 2021
  • Purpose: Some systemic conditions, especially diabetes mellitus (DM), adversely affect dental implant success. This study aimed to investigate the effects of ibuprofen-loaded TiO2 nanotube (ILTN) dental implants in alloxan-induced diabetic rabbits. Methods: Twenty-six New Zealand white rabbits were treated with alloxan monohydrate to induce DM. At 2 weeks following DM induction, 3 types of implants (sandblasted, large-grit, and acid-etched [SLA], ILTN, and machined) were placed into the proximal tibia in the 10 rabbits that survived following DM induction. Each type of implant was fitted randomly in 1 of the holes (round-robin method). The animals were administered alizarin (at 3 weeks) and calcein (at 6 weeks) as fluorescent bone markers, and were sacrificed at 8 weeks for radiographic and histomorphometric analyses. Results: TiO2 nanotube arrays of ~70 nm in diameter and ~17 ㎛ in thickness were obtained, and ibuprofen was loaded into the TiO2 nanotube arrays. A total of 26 rabbits were treated with alloxan monohydrate and only 10 rabbits survived. The 10 surviving rabbits showed a blood glucose level of 300 mg/dL or higher, and the implants were placed in these diabetic rabbits. The implant stability quotient (ISQ) and bone-to-implant contact (BIC) values were significantly higher in the ILTN group (ISQ: 61.8, BIC: 41.3%) and SLA group (ISQ: 62.6, BIC: 46.3%) than in the machined group (ISQ: 53.4, BIC: 20.2%), but the difference in the BIC percentage between the SLA and ILTN groups was not statistically significant (P=0.628). However, the bone area percentage was significantly higher in the ILTN group (78.0%) than in the SLA group (52.1%; P=0.000). Conclusions: The: ILTN dental implants showed better stability (ISQ) and BIC than the machined implants; however, these values were similar to the commercially used SLA implants in the 2-week diabetic rabbit model.