Dorsal calcaneal wedge removal in zadek osteotomy: A cadaveric study.

BACKGROUND: Insertional Achilles tendinopathy (IAT) is a common pathology with multiple surgical interventions available for treatment. The Zadek, dorsal closing wedge calcaneal osteotomy (ZO) has been demonstrated to be effective treatment of IAT. There have been various recommendations in the literature as to what measurement of wedge removal should be considered ideal to produce greatest postoperative range of motion (ROM), thus postoperative biomechanical potential. Accordingly, the purpose of this cadaveric study was to assess the range of motion achieved after various measurements of wedge removal by ZO. METHODS: The ZO was performed on six cadaveric specimens. A 7.5 mm and 15 mm wedge osteotomy was marked and sequentially completed on each specimen. Lateral fluoroscopic imaging was utilized to take preoperative and postoperative ROM measurements for each osteotomy. Dorsiflexion (DF) and plantarflexion (PF) ROM arcs were measured for each wedge size and compared by t-test. Effect sizes were calculated by Cohen's d analysis. RESULTS: Maximal DF was 110.87 ± 12.97 deg in the pre-osteotomy state. Removal of a 7.5 mm wedge improved DF by 8 deg to a mean 102.93 ± 13.81 deg (p = 0.08). Removal of a 15 mm wedge improved DF by 16 deg to a mean 95.96 ± 11.41 deg (p = 0.003). Cohen's d and effect size calculation demonstrated a 7.5 mm wedge to have a small effect on DF, while a 15 mm wedge had a medium effect (0.29, 0.52 respectively). Maximal PF did not change significantly amongst the pre-osteotomy, 7.5 mm wedge, or 15 mm wedge positions. ICC was 0.96. CONCLUSION: Based on the results presented in this study, removal of a 15 mm wedge with ZO yields significant and greater improvement in ROM than a 7.5 mm wedge. We hope the current study will better inform preoperative planning for ZO. STUDY TYPE: Prospective Cadaver Study. LEVEL OF EVIDENCE: V.

Hunger Games: Impact of Fasting Guidelines for Orthopedic Procedural Sedation in the Pediatric Emergency Department.

BACKGROUND: Fasting guidelines for pediatric procedural sedation have historically been controversial. Recent literature suggests that there is no difference in adverse events regardless of fasting status. OBJECTIVES: The goal of this study was to examine adverse outcomes and departmental efficiency when fasting guidelines are not considered during pediatric emergency department (PED) sedation for orthopedic interventions. METHODS: Retrospective chart review identified 2674 patients who presented to a level I PED and required procedural sedation for orthopedic injuries between February 2011 and July 2018. This was a level III, retrospective cohort study. Patients were categorized into the following groups: already within American Society of Anesthesiologists (ASA) fasting guidelines on presentation to the PED (n = 671 [25%]), had procedural sedation not within the ASA guidelines (n = 555 [21%]), and had procedural sedation after fasting in the PED to meet ASA guidelines (n = 1448 [54%]). Primary outcomes were length of stay, time from admission to start of sedation, length of sedation, time from end of sedation to discharge, and adverse events. DISCUSSION: There was a significant difference in the length of stay and time from admission to sedation-both approximately 80 min longer in those with procedural sedation after fasting in the PED to meet ASA guidelines (p < 0.001). There was no significant difference among groups in length of sedation or time to discharge after sedation. Adverse events were uncommon, with only 55 total adverse events (0.02%). Vomiting during the recovery phase was the most common (n = 17 [0.006%]). Other notable adverse events included nine hypoxic events (0.003%) and five seizures (0.002%). There was no significant difference in adverse events among the groups. CONCLUSIONS: Length of stay in the PED was significantly longer if ASA fasting guidelines were followed for children requiring sedation for orthopedic procedures. This is a substantial delay in a busy PED where beds and resources are at a premium. Although providing similar care with equivalent outcomes, the value of spending less time in the PED is evident. Overall, adverse events related to sedation are rare and not related to fasting guidelines.

Periarticular liposomal bupivacaine mixture injection vs. single-shot interscalene block for postoperative pain in arthroscopic rotator cuff repair: a prospective randomized controlled trial.

BACKGROUND: The pain control efficacy, postoperative opioid requirements, and costs among patients undergoing major shoulder surgery using different perioperative analgesia modalities have been topics of active debate. Several studies have compared periarticular injection (PAI) to interscalene block (ISB) in shoulder arthroplasty, but there is a paucity of data comparing them in arthroscopic rotator cuff repair. METHODS: Patients aged 18-80 years with full-thickness rotator cuff tears and undergoing primary arthroscopic rotator cuff repair at 2 different shoulder centers were screened and subsequently randomized to receive either periarticular injection (PAI) of liposomal bupivacaine mixed with 0.25% bupivacaine (n = 41) or single-shot interscalene nerve block (ISB) (n = 36). Visual analog scale (VAS) pain scores, oral morphine equivalent (OME) use, Single Assessment Numerical Evaluation (SANE) scores, and costs were collected. Differences with P <.05 were considered statistically significant. RESULTS: Day of surgery VAS score and OME usage were significantly reduced with ISB vs. PAI (0.69 vs. 4.65, P < .001, and 18.66 vs. 34.39, P < .001, respectively). There were no significant differences between groups regarding VAS score on postoperative days (PODs) 1-3; however, OME usage on PODs 1 (50.5 vs. 38.8, P = .03) and 2 (48.1 vs. 37.8, P = .04) was significantly more in the ISB group. At POD 3, VAS score (4.13 vs. 3.97, P = .60) and OME use (28.60 vs. 31.16, P = .51) were similar. At 6 and 12 weeks, there were also no significant differences between groups regarding VAS and OME use. There was no difference in SANE score at 12 weeks following surgery between groups and no difference between average 12-week cumulative OME use between groups. The average charge for the PAI was $455, and the average charge for ISB was $745. CONCLUSION: Both ISB and PAI provide acceptable pain control following arthroscopic rotator cuff repair. Patients have less pain on the day of surgery with ISB, but rebound pain is significant after the block wears off, resulting in substantially increased opioid use in the first 2 PODs. However, cumulative opioid use between groups was similar. There were also no significant differences at the end of the 12-week episode of care in any of the other variables studied. The charge per patient for PAI is approximately $300 less than ISB. Thus, PAI may offer surgeons and patients an effective postoperative analgesic modality as an alternative to ISB.

Design and synthesis of dalbergin analogues and evaluation of anti-osteoporotic activity.

The chemical modifications of the hydroxyl group of dalbergin have been described via the introduction of cyclic amine, ester and amide groups. Among the twenty-three prepared novel analogues of dalbergin, compound 4d (EC50 2.3µM) showed significantly increased proliferation as assessed by alkaline phosphatase activity and mineralization in calvarial osteoblast cells in vitro. Compound 4d, at a dose of 1.0mg/kg body weight exhibited the significant osteoprotective effect. It showed a significant increase in osteogenic gene expression RunX2 (∼4fold), ALP (∼5fold), OCN (∼4fold) and COL1 (∼4fold) as compared to control group at the same dose in vivo assay.

Neoflavonoids as potential osteogenic agents from Dalbergia sissoo heartwood.

The present study was undertaken to investigate and rationalize the in vitro antiosteoporotic activity of neoflavonoids, isolated from Dalbergia sissoo heartwood. Neoflavonoids were isolated using extensive column chromatography and identified as dalsissooal (1) a new compound and cearoin (2), dalbergin (3), 4-methoxy dalbergion (4), dalbergiphenol (5), dalbergichromene (6), methyl dalbergin (7) and latinone (8) as known compounds by comparison their spectroscopic data with those reported in the literature. Among the screened compounds, compounds 1, 3, 5-8 significantly increased proliferation as assessed by alkaline phosphatase activity and mineralization in calvarial osteoblast cells.

Comparison of 2-Octyl Cyanoacrylate with Prolene (4-0) Sutures in Extra Oral Wound Closure.

Aim: To compare the healing following various maxillofacial incisions using 2-octyl cyanoacrylate (2-OCA) and prolene (4-0) sutures. Objective: To evaluate the complications and aesthetic outcome of the incision wounds after closure using 2-OCA and prolene (4-0) sutures. Materials and Methods: The patient undergoing an extraoral incision was evaluated for pain, inflammation, infection, dehiscence, scar, and surface texture. In Group I, 15 patient incisions were closed with 2-OCA and in Group II, 15 patient incisions were closed with prolene (4-0) suture. Result: A few patients experienced pain with Group I and then Group II, but infection, inflammation, and dehiscence were more in Group I than in Group II. Conclusion: A cosmetic outcome was higher in the cyanoacrylate group, and the surface texture was satisfying in the same group.

Synthesis of novel imbricatolic acid analogues via insertion of N-substituted piperazine at C-15/C-19 positions, displaying glucose uptake stimulation in L6 skeletal muscle cells.

A new class of N-substituted piperazine analogues of imbricatolic acid have been designed and synthesized by using the appropriate synthetic routes in excellent yield. All synthesised compounds were screened for their in vitro glucose uptake stimulatory activity. Among them compounds 4b, 4e, 8b, and 8e triggered L6 skeletal muscle cells for glucose uptake at 54.73%, 40.79%, 40.90%, and 39.55% stimulation, respectively. Compound 4b has emerged as important lead compound showing potential antidiabetic activity. Illustration about their synthesis and in vitro glucose uptake activity is described.

Efficacy of Postoperative Oral Antibiotics in Foot and Ankle Surgery.

BACKGROUND: Preoperative oral antibiotic use in patients undergoing foot and ankle surgery is standard practice, but no consensus has been reached regarding the efficacy of postoperative oral antibiotics. The purpose of this study was to determine whether postoperative oral antibiotics reduce the rate of surgical site infections (SSIs) in patients, with and without comorbidities, undergoing foot and ankle surgery. METHODS: A retrospective chart review was conducted identifying patients who underwent foot and ankle surgery by 4 fellowship-trained, foot and ankle orthopaedic surgeons between January 1, 2015, and January 1, 2019. Patients were divided into 2 groups: those who received postoperative oral antibiotics (group 1) and those who did not (group 2). Two surgeons routinely prescribed postoperative oral antibiotics, and 2 did not. Demographics, comorbidities, and procedure complexity based on surgical site and Current Procedural Terminology code were recorded from the charts. The primary outcome was postoperative infection (superficial or deep) within 6 months after surgery. Patients with antibiotic use prior to surgery, preoperative infection, or lack of follow-up >6 weeks were excluded. Multivariate logistic regression modeling was used to analyze differences in infection rate and severity. RESULTS: Chart review identified 3631 patients, 1227 of whom did not receive postoperative oral antibiotics whereas 2394 patients did. Routine postoperative oral antibiotic use did not significantly affect postoperative infection rates or severity. However, all covariates studied (diabetes, hypertension, obesity, tobacco use, alcohol use, rheumatoid conditions, and age) influenced postoperative infection rates and severity. CONCLUSION: The results of this study indicate that postoperative oral antibiotics are not associated with differences in infection rates or severity. We do not recommend routine use in foot and ankle surgery.

A butanolic fraction from the standardized stem extract of Cassia occidentalis L delivered by a self-emulsifying drug delivery system protects rats from glucocorticoid-induced osteopenia and muscle atrophy.

We recently reported that a butanol soluble fraction from the stem of Cassia occidentalis (CSE-Bu) consisting of osteogenic compounds mitigated methylprednisone (MP)-induced osteopenia in rats, albeit failed to afford complete protection thus leaving a substantial scope for further improvement. To this aim, we prepared an oral formulation that was a lipid-based self-nano emulsifying drug delivery system (CSE-BuF). The globule size of CSE-BuF was in the range of 100-180 nm of diluted emulsion and the zeta potential was -28 mV. CSE-BuF enhanced the circulating levels of five osteogenic compounds compared to CSE-Bu. CSE-BuF (50 mg/kg) promoted bone regeneration at the osteotomy site and completely prevented MP-induced loss of bone mass and strength by concomitant osteogenic and anti-resorptive mechanisms. The MP-induced downregulations of miR29a (the positive regulator of the osteoblast transcription factor, Runx2) and miR17 and miR20a (the negative regulators of the osteoclastogenic cytokine RANKL) in bone was prevented by CSE-BuF. In addition, CSE-BuF protected rats from the MP-induced sarcopenia and/or muscle atrophy by downregulating the skeletal muscle atrogenes, adverse changes in body weight and composition. CSE-BuF did not impact the anti-inflammatory effect of MP. Our preclinical study established CSE-BuF as a prophylactic agent against MP-induced osteopenia and muscle atrophy.

Characterization of genetically complex Collaborative Cross mouse strains that model divergent locomotor activating and reinforcing properties of cocaine.

RATIONALE: Few effective treatments exist for cocaine use disorders due to gaps in knowledge about its complex etiology. Genetically defined animal models provide a useful tool for advancing our understanding of the biological and genetic underpinnings of addiction-related behavior and evaluating potential treatments. However, many attempts at developing mouse models of behavioral disorders were based on overly simplified single gene perturbations, often leading to inconsistent and misleading results in pre-clinical pharmacology studies. A genetically complex mouse model may better reflect disease-related behaviors. OBJECTIVES: Screening defined, yet genetically complex, intercrosses of the Collaborative Cross (CC) mice revealed two lines, RIX04/17 and RIX41/51, with extreme high and low behavioral responses to cocaine. We characterized these lines as well as their CC parents, CC004/TauUnc and CC041/TauUnc, to evaluate their utility as novel model systems for studying the biological and genetic mechanisms underlying behavioral responses to cocaine. METHODS: Behavioral responses to acute (initial locomotor sensitivity) and repeated (behavioral sensitization, conditioned place preference, intravenous self-administration) exposures to cocaine were assessed. We also examined the monoaminergic system (striatal tissue content and in vivo fast scan cyclic voltammetry), HPA axis reactivity, and circadian rhythms as potential mechanisms for the divergent phenotypic behaviors observed in the two strains, as these systems have a previously known role in mediating addiction-related behaviors. RESULTS: RIX04/17 and 41/51 show strikingly divergent initial locomotor sensitivity to cocaine with RIX04/17 exhibiting very high and RIX41/51 almost no response. The lines also differ in the emergence of behavioral sensitization with RIX41/51 requiring more exposures to exhibit a sensitized response. Both lines show conditioned place preference for cocaine. We determined that the cocaine sensitivity phenotype in each RIX line was largely driven by the genetic influence of one CC parental strain, CC004/TauUnc and CC041/TauUnc. CC004 demonstrates active operant cocaine self-administration and CC041 is unable to acquire under the same testing conditions, a deficit which is specific to cocaine as both strains show operant response for a natural food reward. Examination of potential mechanisms driving differential responses to cocaine show strain differences in molecular and behavioral circadian rhythms. Additionally, while there is no difference in striatal dopamine tissue content or dynamics, there are selective differences in striatal norepinephrine and serotonergic tissue content. CONCLUSIONS: These CC strains offer a complex polygenic model system to study underlying mechanisms of cocaine response. We propose that CC041/TauUnc and CC004/TauUnc will be useful for studying genetic and biological mechanisms underlying resistance or vulnerability to the stimulatory and reinforcing effects of cocaine.

New lignan glycosides from Cissus quadrangularis stems.

Phytochemical investigation of Cissus quadrangularis stems led to the isolation of one new phenolic glycoside (1) and two new lignan glycosides (7 & 8) along with twelve known compounds (2-6 & 9-15). Their chemical structures were determined on the basis of extensive spectroscopic analysis using 1D, 2D NMR, and mass spectrometric analysis. Among the known compounds, 4-6, 9 and 12 were isolated for the first time from the genus Cissus whereas compounds 10, 11 and 13 for the first time from this plant.

Systems genetics of sensation seeking.

Sensation seeking is a multifaceted, heritable trait which predicts the development of substance use and abuse in humans; similar phenomena have been observed in rodents. Genetic correlations among sensation seeking and substance use indicate shared biological mechanisms, but the genes and networks underlying these relationships remain elusive. Here, we used a systems genetics approach in the BXD recombinant inbred mouse panel to identify shared genetic mechanisms underlying substance use and preference for sensory stimuli, an intermediate phenotype of sensation seeking. Using the operant sensation seeking (OSS) paradigm, we quantified preference for sensory stimuli in 120 male and 127 female mice from 62 BXD strains and the C57BL/6J and DBA/2J founder strains. We used relative preference for the active and inactive levers to dissociate preference for sensory stimuli from locomotion and exploration phenotypes. We identified genomic regions on chromosome 4 (155.236-155.742 Mb) and chromosome 13 (72.969-89.423 Mb) associated with distinct behavioral components of OSS. Using publicly available behavioral data and mRNA expression data from brain regions involved in reward processing, we identified (a) genes within these behavioral QTL exhibiting genome-wide significant cis-eQTL and (b) genetic correlations among OSS phenotypes, ethanol phenotypes and mRNA expression. From these analyses, we nominated positional candidates for behavioral QTL associated with distinct OSS phenotypes including Gnb1 and Mef2c. Genetic covariation of Gnb1 expression, preference for sensory stimuli and multiple ethanol phenotypes suggest that heritable variation in Gnb1 expression in reward circuitry partially underlies the widely reported relationship between sensation seeking and substance use.

Extract and fraction of Cassia occidentalis L. (a synonym of Senna occidentalis) have osteogenic effect and prevent glucocorticoid-induced osteopenia.

ETHNOPHARMACOLOGICAL RELEVANCE: Cassia occidentalis L., a synonym of Senna occidentalis (belongs to Caesalpiniaceae family) is an annual plant. Pursuing a lead from a folk practice prevalent since the late nineteenth century in Andhra Pradesh, a Southern state of India, of use of Cassia occidentalis leaf and stem for treating patients with fracture and bone diseases, we have not only confirmed its fracture healing activity but also demonstrated efficacy in preventing glucocorticoid-induced osteoporosis (GIO), the commonest form of medication-induced bone loss caused chiefly due to impairment of bone formation. AIM OF THE STUDY: In the present work, the effects of extract and fraction of leaf and stem of Cassia occidentalis was investigated in fracture healing and GIO models of rat. The study also aimed to identify osteogenic compounds from this plant. MATERIALS AND METHODS: Ethanolic extracts from leaf and stem of Cassia occidentalis were prepared and their efficacy tested in rat femur osteotomy (fracture healing) model. Subsequently, a butanolic fraction was prepared and osteogenic efficacy compared with the ethanolic extract, and upon finding the former to be more potent, its osteogenic effect was studied in details in GIO model. Chemical finger-printing and isolation of ten pure compounds were done to assess their osteogenic effect in rat primary osteoblast cultures. RESULTS: Ethanolic extract of stem was more effective than the leaf extract in enhancing bone regeneration at the site of osteotomy. Further, butanolic fraction of the ethanolic extract of stem was more effective than the later in bone regeneration at the femur osteotomy site and in preventing bone loss in GIO model. The mechanism of skeletal preservation involved stimulation of new bone formation and inhibition of bone resorption. As many as six osteogenic compounds were isolated out of which apigenin-6C-glucopyranoside was most effective in vitro. CONCLUSION: Our study found that a standardized extract of an ethanolic extract and its butanolic fraction from the stem of Cassia occidentalis has osteogenic as well as anti-resorptive effects, resulting in the protection against glucocorticoid-induced bone loss. Our results contribute towards validation of the traditional use of Cassia occidentalis in fracture healing and also suggest its beneficial use in GIO for which clinical trials are warranted.

Ethanolic extract of Dalbergia sissoo promotes rapid regeneration of cortical bone in drill-hole defect model of rat.

Leaves of Dalbergia sissoo is known to have protective actions against postmenopausal bone loss in rat. In this study, we have evaluated the fracture healing properties of ethanolic extract (EE) of Dalbergia sissoo leaves. To observe the fracture healing property in the drill-hole injury model, we randomly divided total 32 adult female Sprague Dawley rats (180±200g) into 4 groups: (i) Control operated group; (ii) EE (250mg/kg/day); (iii) EE (500mg/kg/day) and (iv) EE (1000mg/kg/day). The right femora were fractured at the mid-diaphysis region and each group of rats received their respective treatment for 15days. Ethanol extract dose dependently induced bone regeneration at the fracture site assessed by fluorochrome labeling. All of three doses, 250mg/kg/day dose significantly increased bone volume fraction, trabecular thickness, trabecular number, and connectivity density and decreased trabecular separation in bone. Furthermore, the extract induced the expression of osteogenic genes including BMP-2, BMP-4, RunX-2 and COL-1 compared to the control group. The EE improved fracture healing much earlier (day 15) than the normal healing process, as assessed by the increased callus volumes and mineralized nodule formation. This extract is found beneficial in fracture healing of rat.

Heartwood extract from Dalbergia sissoo promotes fracture healing and its application in ovariectomy-induced osteoporotic rats.

OBJECTIVES: This study was undertaken to investigate the effects of a heartwood ethanolic extract (HEE) made from the Dalbergia sissoo on facture healing and in the prevention of pathological bone loss resulting from estrogen deficiency in ovariectomized (Ovx) rats. METHODS: Heartwood ethanolic extract (250, 500 and 1000 mg/kg per day) was administered orally immediately next day after drill-hole injury and continued for 2 weeks. Ovx rats received HEE at same doses for 12 weeks and compared with 17-ß estradiol (E2; 100 µg/kg for 5 days/week subcutaneously) group. Confocal imaging for fracture healing, micro-architecture of long bones, biomechanical strength, formation of mineralized nodule by bone marrow osteoprogenitor cells, bone turnover markers and gene expression were studied. One-way ANOVA was used to test significance. KEY FINDINGS: Heartwood ethanolic extract treatment promoted fracture healing, formation of new bone at the drill-hole site and stimulated osteogenic genes at callus region. HEE administration to the Ovx rats exhibited better micro-architectural parameters at various anatomical positions, better bone biomechanical strength and more osteoprogenitor cells in the bone marrow compared with Ovx + vehicle group. HEE exhibited no uterine estrogenicity. CONCLUSIONS: Oral administration of HEE was found to promote fracture healing and exhibited osteoprotective effect by possibly stimulation of osteoblast function.

A neoflavonoid dalsissooal isolated from heartwood of Dalbergia sissoo Roxb. has bone forming effects in mice model for osteoporosis.

Dalbergia sissoo Roxb. is a well known medicinal plant of India, enriched with various flavonoids used for treating multiple diseases. Earlier, we have shown that extract of Dalbergia sissoo Roxb. leaves mitigate ovariectomy induced bone loss and pure compounds (neoflavonoids) isolated from it, promote osteoblastogenesis in primary calvarial osteoblasts cells in vitro. Here, we hypothesize that dalsissooal (DSL), a novel neoflavonoid isolated from the heartwood of Dalbergia sissoo Roxb. is an important constituent of the extract that imparts bone forming effects. Treatment with DSL enhanced trabecular bone micro-architecture parameters, biomechanical strength, increased bone formation rate and mineral apposition rate in OVx mice comparable to 17ß-estradiol. It increased bone formation by enhancing osteoblast gene expression and reduced bone turnover by decreasing osteoclastic gene expressions. Interestingly, we observed that DSL has no uterine estrogenic effects. At cellular levels, DSL promoted differentiation of bone marrow cells as well as calvaria osteoblast cells towards osteoblast lineage by enhancing differentiation and mineralizing ability to form mineralizing nodules via stimulating BMP-2 and RunX-2 expressions. Overall, our data suggest that oral supplementation of a novel neoflavonoid dalsissooal isolated from heartwood of Dalbergia sissoo Roxb. exhibited bone anabolic action by improving structural property of bone, promoting new bone formation and reducing bone turnover rate in post-menopausal model for osteoporosis with no uterine hyperplasia.

Fast and long acting neoflavonoids dalbergin isolated from Dalbergia sissoo heartwood is osteoprotective in ovariectomized model of osteoporosis: Osteoprotective effect of Dalbergin.

OBJECTIVE: This study aims to evaluate the skeletal effects of dalbergin (DBN), isolated from Dalbergia sissoo heartwood, in ovariectomized (OVx) BALB/c mice, a postmenopausal osteoporosis model of bone loss. METHODS: Adult BALB/c mice were used and randomly assigned in to six groups with 6 animals (n=6) in each group: sham (surgery operated without ovariectomy) with vehicle, ovariectomy with vehicle, ovariectomy (OVx) with estradiol (E2 5.0µgkg-1day-1), or ovariectomy with dalbergin at three different doses of DBN (1.0, 5.0 and10mgkg-1day-1). Daily oral administration of the vehicle, estradiol, or DBN was started 8 weeks post-surgery and continued for 8 weeks. At the end of experiment, mice were sacrificed and assessed for trabecular bone structure of tibia, lumbar vertebra (L5) and alterations in biochemical and uterine parameters, pharmacokinetic profile and gene expression were monitored for each group. RESULTS: Treatment with DBN prevented trabecular bone loss in cancellous bone in the tibial metaphysis and lumbar vertebra region of the ovariectomized mice. Micro-CT data showed that mice treated with DBN at 1.0mgkg-1day-1 exhibited improved bone micro-architecture that was sustained with decreased expression of bone resorption markers like TRAP and RANK and caused an increase in osteogenic markers like RUNX2, BMP2 and OPG/RANKL ratio compared with OVx+vehicle treated mice. Moreover, DBN treatment induced no uterine estrogenicity and significantly lowered the osteocalcin amount in serum when compared with OVx+V group. DBN reached its maximum concentration (Cmax) 238.49±21.37ngml-1 in serum as early as 1h of administration. Overall, DBN (1.0mgkg-1day-1) treatment exhibited similar bone conserving effect against bone-loss as estradiol treatment. CONCLUSION: Daily oral administration of DBN for 8 weeks showed significant anabolic effects on bone micro-architectural parameters along with down regulation of bone resorptive markers without compromising safety at uterine level. Therefore, our study provides basis for DBN as a therapeutic candidate against postmenopausal osteoporosis.

Neoflavonoid dalbergiphenol from heartwood of Dalbergia sissoo acts as bone savior in an estrogen withdrawal model for osteoporosis.

OBJECTIVE: Dalbergiphenol (DGP) is a neoflavonoid isolated from heartwood of Dalbergia sissoo. Effects of DGP on skeletal health remain to be elucidated. The objective of the present study was to investigate the biological effects of DGP on bone loss in ovariectomized mice. METHODS: Adult BALB/c mice were ovariectomized and administered DGP (1 and 5  mg/kg/d) or 17ß-estradiol (E2) orally for 6 weeks. The sham group and the ovariectomy (OVX) + vehicle group served as controls. Eight female BALB/c mice were taken for each group. Uterine estrogenicity, bone microarchitecture, biomechanical strength, new bone formation (based on bone formation rate and mineral apposition rate), and skeletal expression of osteogenic and resorptive gene markers were studied. RESULTS: OVX resulted in a marked increase in body weight and a decrease in femoral and vertebral trabecular bone volume that were prevented by DGP or E2 treatment. DGP treatment increased bone biomechanical strength and new bone formation rate in ovariectomized mice, comparable with E2 treatment. However, increase in uterine weight and estrogenicity were observed in E2-treated ovariectomized mice, but not in response to DGP treatment. Treatment with DGP increased messenger RNA expression of runt-related transcription factor 2, osterix, and collagen type I, and decreased messenger RNA expression of tartrate-resistant acid phosphatase and the osteoprotegerin-to-receptor activator of nuclear factor-κB ligand ratio in the femur of ovariectomized mice. CONCLUSIONS: Overall findings suggest that DGP treatment can effectively prevent OVX-induced increase in bone loss and decrease in bone strength possibly by increasing osteoblastic activities and by decreasing osteoclastic activities.

Study of conformational stability, structural, electronic and charge transfer properties of cladrin using vibrational spectroscopy and DFT calculations.

In the present work, a detailed conformational study of cladrin (3-(3,4-dimethoxy phenyl)-7-hydroxychromen-4-one) has been done by using spectroscopic techniques (FT-IR/FT-Raman/UV-Vis/NMR) and quantum chemical calculations. The optimized geometry, wavenumber and intensity of the vibrational bands of the cladrin in ground state were calculated by density functional theory (DFT) employing 6-311++G(d,p) basis sets. The study has been focused on the two most stable conformers that are selected after the full geometry optimization of the molecule. A detailed assignment of the FT-IR and FT-Raman spectra has been done for both the conformers along with potential energy distribution for each vibrational mode. The observed and scaled wavenumber of most of the bands has been found to be in good agreement. The UV-Vis spectrum has been recorded and compared with calculated spectrum. In addition, 1H and 13C nuclear magnetic resonance spectra have been also recorded and compared with the calculated data that shows the inter or intramolecular hydrogen bonding. The electronic properties such as HOMO-LUMO energies were calculated by using time-dependent density functional theory. Molecular electrostatic potential has been plotted to elucidate the reactive part of the molecule. Natural bond orbital analysis was performed to investigate the molecular stability. Non linear optical property of the molecule have been studied by calculating the electric dipole moment (µ) and the first hyperpolarizability (ß) that results in the nonlinearity of the molecule.