Assessment of biogrowth assemblages with depth in a seawater intake system of a coastal power station.

Marine biogrowth infestation of a seawater intake system was investigated. A digital camera fixed onto a skid was used to record the biogrowth at intervals of 5 m up to a depth of 55 m. Divers inspected the intake shaft and collected the biogrowth samples for biomass estimation. A biomass density of 7.5 kg m-2 and 28.2 kg m-2 was recorded at 5 and 30 m depths respectively. Inspection by the divers revealed that hard-shelled organisms such as oysters and brown and green mussels were observed in plenty up to a thickness of 15 cm and bryozoans grew as epibionts. At lower depths (<40 m), hydroids grew on the shells of green mussels along with silt accumulation. The biofouling community was composed of 46 organisms, exhibiting variation in distribution and abundance. The study explains the extent and type of marine biogrowth phenomena with depth and describes biofouling preventive methods.Supplemental data for this article is available online at https://doi.org/10.1080/08927014.2021.1933457 .

Insecticidal property of Ocimum essential oil embedded polylactic acid packaging films for control of Sitophilus oryzae and Callosobruchus chinensis.

Naturally derived essential oils (EOs) from Ocimum basilicum (OB) and Ocimum gratissimum (OG) were incorporated in polylactic acid (PLA) matrix with concentration of 2.5 % and 5 % respectively by solvent casting method, with an aim to develop insecticidal polymer pouches (insect proof polymer pouches). The major components following GC-MS analysis revealed the presence of EOs as estragole (69.998 %) in OB and thymol (29.843 %) in OG. The developed films with EOs showed remarkable insecticidal activity with 100 % and 80 % mortality rate for OB and OG respectively at 2.5 % concentration against rice weevil (Sitophilus oryzae). While, both OB and OG EOs observed 100 % mortality against pulse beetle (Callosobruchus chinensis) after 96 h exposure in presence of grain conditions and the insecticidal efficacy was equivalent to the commercial hermetic bags (CSB). The physical property of film showed increase in the film thickness in EO-PLA films whereas the mechanical properties of EO-PLA films matrix have increased the polymer flexibility with decreasing tensile strength (TS) and Youngs modulus (EM) as TS OB 5 %, OG 5 % - 15.64 MPa, 17.66 MPa respectively. While, water vapour transmission rate (WVTR) was reduced to 0.015 g/m2.hr, optical characteristics showed slight significant change in colour and FTIR spectra exhibited a change in -OH stretching compared to blank PLA matrix. The surface morphology of the blank and EO embedded PLA films visualized by SEM depicted a complete homogenization of essential oils in the PLA matrix.

Feasibility of polylactic acid and essential oil composite with insecticidal properties for prevention of Sitophilus oryzae and Oryzophilus surinamensis in Sorghum and Pearl millet.

Current study provides insight on the feasibility of polylactic acid (PLA) integrated with (1:1 ratio) of essential oils belonging to Ocimum gratissimum (OG) and Mentha spicata (MS) for prevention of major stored insect pests (Sitophilus oryzae and Oryzophilus surinamensis) in Sorghum and Pearl millet. A combination of OG and MS essential oils (1:1) was incorporated into the PLA polymer matrix. Further, SPME analysis of synthesized PLA showed the presence of volatiles corresponding to carvone (6.44 %) and thymol (6.22 %). Synthesized PLA composites were tested against S. oryzae and O. surinamensis using Sorghum and Pearl millets, and insect mortality was equivalent to commercial super bags (CSB). The head space oxygen decreased significantly in CSB and slightly in PLA bags. Thickness of EO blended PLA composite was increased (99 µm), tensile strength (23.94 MPa), WVTR (1.42 g/m2.hr) analysis, significant folding ability, and swelling capacity (0.24 %) showed slight reduction in composite film. TGA showed good thermal stability (334˚C) and XRD displayed the increased crystallinity (38.35 %) in PLAOM films, SEM and FTIR analysis of the synthesized composite films revealed complete homogenization of EO and PLA matrix. In addition, SEM analysis of insects (control & treated) revealed less topology changes in the elytra. Biodegradability study confirmed the weight loss in PLA films. Hence, current approach of using composite EO's with PLA offers sustainable solution for prevention of infestation during storage of millets.

Development and application of active films for food packaging using antibacterial peptide of Bacillus licheniformis Me1.

AIMS: An attempt was made to evaluate the effectiveness of partially purified antibacterial peptide (ppABP) produced by Bacillus licheniformis Me1 for food preservation by means of active packaging. METHODS AND RESULTS: The active packaging films containing ppABP were developed using two different packing materials [low-density polyethylene (LDPE) and cellulose films] by two different methods: soaking and spread coating. The activated films showed antibacterial activity against pathogens. The release study of ppABP from coated film showed that the LDPE films liberated ppABP as soon as it comes in contact with water, while gradual release of coated ppABP was observed in case of cellulose films. The activated films showed residual activity in different simulating conditions, such as pH of food and storage temperatures. The activated films demonstrated its biopreservative efficacy in controlling the growth of pathogens in cheese and paneer. CONCLUSIONS: The ppABP-activated films were found to be effective for biopreservation. The ppABP from active films got diffused into the food matrix and reduced the growth rate and maximum growth population of the target micro-organism. SIGNIFICANCE AND IMPACT OF THE STUDY: Both types of ppABP-activated films can be used as a packaging material to control spoilage and pathogenic organisms in food, thereby extending the shelf life of foods.

Prevalence of preoperative anxiety in patients posted for surgical procedures and its relation to the doses of anesthetic drugs: A cross-sectional study.

Background: In patients undergoing surgical procedures, preoperative period is one of the most worrying periods. There are only few studies which revealed that increased preoperative anxiety is associated with increased requirements of doses of anesthetic agents. Aim: The aim of this study is to assess the prevalence of preoperative anxiety in patients posted for surgical procedures and its relation to the doses of anesthetic drugs. Materials and Methods: This is a cross-sectional, analytical study done between January 2021 and April 2021. A total of 100 patients undergoing surgery have given consent to participate in the study by filling self-designed questionnaire, Amsterdam Preoperative Anxiety and Information Scale (APAIS). Data analysis was done by SPSS version 24 using appropriate statistical tests. Results: Preoperative anxiety was noted in 21% of the patients who were undergoing surgery. The association between preoperative anxiety and need for increase in the doses of anesthetic agents during intraoperative period was found to be statistically significant (P < 0.004). Conclusion: A significant number of patients required increased amounts of anesthetic drugs to reduce anxiety during intraoperative period. Therefore, appropriate methods have to be introduced to address the concerns of patients undergoing surgery and thereby reducing anxiety.

A Rare Case Report of an Acute Orbit.

Orbital complications of rhino-sinusitis was one of the most common extracranial complications in the pre-antibiotic era. However, the incidence of intra-orbital complications secondary to rhinosinusitis has significantly decreased in recent times with the advertent usage of broad-spectrum antibiotics. The subperiosteal abscess is one of the most common intraorbital complications of acute rhinosinusitis. This is a case report of a 14-year-old girl who presented with diminished vision and ophthalmoplegia which on evaluation was diagnosed to be a case of a subperiosteal abscess. The patient was treated by endoscopic sinus surgery and with complete post-operative recovery to normal vision and ocular movements. This report aims at describing the presentation and management of the condition.

Antidiabetic Effect of GII Compound Purified from Fenugreek (Trigonella foenum graecum Linn) Seeds in Diabetic Rabbits.

Aim is to study the antidiabetic effect of a compound GII purified earlier from the water extract of fenugreek (Trigonella foenum graecum) seeds by Murthy and his colleagues (patented in India and USA) in diabetic rabbits. Diabetes was induced in rabbits by injecting 80 mg/kg bw of alloxan intravenously into rabiits. Rabbits were subdivided into subdiabetic [fasting blood sugar (FBG) up to 120 mg/dl with abnormal glucose tolerance in glucose tolerance test (GTT)], moderately diabetic (FBG below 250 mg/dl) and severely diabetic (FBG above 250 mg/dl). Blood glucose and glycosylated hemoglobin (HbA1C) were estimated by procedures in the kits of Stangen Immunodiagnostics, Mumbai using, respectively, glucose oxidase method and absorbance at 415 nm. Serum insulin was estimated by the ELISA method as described in the kit of Boehringer Mannheim Immunodiagnostics, Mumbai, India. GII was found to improve blood glucose utilization in GTT and reduced FBG and HbA1C. In the present communication detailed studies were carried out with GII in the subdiabetic, moderately diabetic and severely diabetic rabbits. GII at a dose of 50 mg/kg bw per day brought down the elevated FBG levels in the untreated subdiabetic (FBG 96.6 ± 7 mg/dl), moderately diabetic (150.1 ± 14 mg/dl) and severely diabetic rabbits (427 ± 46 mg/dl) to normal in 12, 15 and 28 days of treatment. It improved serum HbA1C and insulin levels also in these rabbits. Intermittent therapy once a week for 6 weeks with GII at the same dose brought down the FBG values to normal in the subdiabetic (FBG 96.0 ± 2 mg/dl) and in the moderately diabetic rabbits to 133.0 ± 12 mg/dl. After stopping therapy of the subdiabetic and moderately diabetic rabbits whose FBG values came to normal after treatment with GII 50 mg/kg bw, the values remained normal for 1 week and showed a tendency to increase only after 15 days. If these animal studies are applicable to humans these results indicate that a diabetic person need not take GII daily when once the FBG value comes to normal or near to normal. Patients might be able to take GII only when the FBG value shows tendency to increase. So, intermittent therapy is possible with the potent product GII of the fenugreek seeds which is of a great advantage.

Hyoid Chondroma.

Mass lesions of the larynx are one of the most common clinical entity which we come across in routine otorhinolaryngology and head neck practice with varied symptomatology. Among all the mass lesions of the larynx, Epithelial neoplasms constitute up to 97%. Mesenchymal tumours of the larynx constitute only 0.3-1.0% of all the laryngeal tumors. Abundance of cartilage structures in the larynx made it a spot for mesenchymal tumors [chondromas and chandrosacrcomas]. The spectrum of mesenchymal neoplasms can vary from chondromas, chondroblastoma to chondrosarcoma. Here we want to share our experience of a mesenchymal tumour of the larynx. This case is reported for the rarity and ambiguity in diagnosis. Though these are slow-growing tumours with an early presentation, in our case, the patient had a supportive tracheostomy without definitive treatment for more than 2 years. We managed this patient by excising the mass by lateral pharyngotomy with the preservation of larynx followed by successful Decannulation in 20 days.

Management of Cervical Tracheo-Esophageal Fistula by Lateral Cervical Approach: Our Experience'.

Acquired Tracheo-esophageal fistula (TEF) is a challenging and complicated condition. The laryngeal protection is lost in acquired TEF cases due to the established connection between the esophagus and the airways leading to aspiration, pneumonia, and acute respiratory distress syndrome. Malignancy contributes to about 80% of acquired TEF. Nonmalignant causes for TEF include prolonged ventilation, trauma (iatrogenic, penetrating, or blunt injury), foreign bodies, corrosive burns, and granulomatous infections. With the advancements in critical care, the incidence of TEF post-ventilation is on the rise in recent decades. We would like to share our experience managing ten cases of nonmalignant acquired cervical TEF by the lateral cervical approach at our institute. Apart from the isolated TEF cases, one patient with concomitant tracheal stenosis was repaired simultaneously with good postoperative results. TEF was identified in two cases following removal of T-tube and solid stent respectively and was repaired successfully with lateral cervical approach with strap muscle flap interposition.

Anti-hyperglycemic compound (GII) from fenugreek (Trigonella foenum-graecum Linn.) seeds, its purification and effect in diabetes mellitus.

An anti-hyperglycemic compound named GII was purified from the water extract of the seeds of fenugreek (T. foenum-graecum) and shown to be different from trigonelline and nicotinic acid isolated earlier from the same plant. GII (50 mg/kg body weight, po) reduced blood glucose in glucose tolerance test (GTT) in the sub-diabetic and moderately diabetic rabbits and significantly reduced the area under the curve (AUC) of GTT. Treatment for 7 days of the sub-diabetic rabbits with GII (50 mg/kg body weight, po) improved glucose tolerance without reducing fasting blood glucose (FBG) which was nearly normal. The results suggest that there is no risk of hypoglycemia in near normal animals (may be humans also) with abnormal GTT. Treatment of the moderately diabetic rabbits with GII (100 mg/kg body weight for 3 weeks) reduced FBG to nearly normal value and improved GTT. GII was more effective than the standard drug tolbutamide. Intermittent therapy given on days 1-5, 11-15, 26-30 and 56-60 to moderately diabetic rabbits leaving in between days without treatment brought down FBG to normal and AUC during GTT was normal. After 15 days treatment with GII (100 mg/kg body weight for 3 weeks) glycosylated hemoglobin came down and insulin increased to normal values in the sub-diabetic, moderately diabetic and severely diabetic rabbits. GII treatment (100 mg/kg body weight for 15 days) brought down all the altered serum lipids (TC, HDLC, TAG, PLs and FFAs) to normal levels. The results suggest that intermittent therapy, instead of daily therapy is possible and GII has good potential as an oral anti-diabetic drug with intermittent therapy.

Mechanism of anti-diabetic action, efficacy and safety profile of GII purified from fenugreek (Trigonella foenum-graceum Linn.) seeds in diabetic animals.

Mechanism of action of GII (100 mg/kg body weight, po for 15 days) purified from fenugreek (T. foenum-graecum) seeds was studied in the sub-diabetic and moderately diabetic rabbits. In the sub-diabetic rabbits it did not change much the content of total lipids, glycogen and proteins in the liver, muscle and heart (glycogen was not studied in the heart). However, in the moderately diabetic rabbits same treatment decreased total lipids more in the liver (21%) than those in the heart and muscle. Total protein content increased (14%) in the liver but negligible change (5-7%) was observed in heart and muscle. Glycogen increased (17%) in the liver but not in the muscle of the moderately diabetic rabbits (glycogen was not estimated in the heart). Among the enzymes of glycolysis, activity of glucokinase was not affected in the liver of both the sub-diabetic and moderately diabetic rabbits. Phosphofructokinase and pyruvate kinase activity in both sub-diabetic and moderately diabetic rabbits increased (13-50%) indicating stimulation of glycolysis. The activity of gluconeogenic enzymes glucose-6-phosphatase and fructose-1,6-diphosphatase of the sub-diabetic rabbits decreased in the liver (15-20%) but not in the kidneys. In the moderately diabetic rabbits after treatment with GII, glucokinase in the liver was not affected much (-9%) but increased well in the muscle (40%). Phosphofructokinase and pyruvate kinase were moderately increased both in the liver and the muscle (18-23%). The gluconeogenic enzyme glucose-6-phosphatase decreased reasonably well in the liver and kidneys (22, 32%). Fructose-1,6-diphosphatase decreased only slightly (10, 9%) in the moderately diabetic rabbits. Thus GII seems to decrease lipid content of liver and stimulate the enzymes of glycolysis (except glucokinase) and inhibit enzymes of gluconeogenesis in the liver of the diabetic especially moderately diabetic rabbits.

Osteogenic activity of constituents from Butea monosperma.

Phytochemical investigation from the stem bark of Butea monosperma, led to the isolation and identification of three new compounds named buteaspermin A (1), buteaspermin B (2) and buteaspermanol (3), along with 19 known compounds. The structure of compounds 1-22 were established on the basis of their spectroscopic data. The isolated compounds 2-17 were evaluated using neonatal (1-3 day old) rat calvaria derived primary osteoblast cultures. Five of these compounds 7, 10-13 showed promising osteogenic activity, attributed to increased osteoblast proliferation, differentiation and mineralization as evidenced by marked increase in expression of alkaline phosphatase, an early phase differentiation marker, and alizarin Red S staining of osteoblasts cultured for 48 h and von Kossa silver staining of nodules formed 15 days after culture with these compounds. Quantification of mineralization by optical density measurement of Alizarin Red S extracted from stained osteoblasts cultured for 7 days in presence of these compounds showed significant (P<0.05, vs corresponding vehicle control group) increase in mineralization. On the basis of biological results, structure-activity relationships are discussed.

Perceived stress, anxiety, and coping states in medical and engineering students during examinations.

AIM: This study aims to study the factors associated with stress, anxiety, and coping states in students of 1st and 2nd year in medical and engineering colleges during examinations. MATERIALS AND METHODS: This prospective, longitudinal study was conducted on 200 undergraduate medical and engineering students from 1st to 2nd year (50 in each year), after obtaining ethical approval from the institutional ethics committee. All the participants gave written informed consent. All students filled a questionnaire which consisted of a general information sheet, perceived stress scale, Hamilton Anxiety Rating Scale, brief COPE inventory, and sources of stress questionnaire 1 month before and 1 month after their university examinations. Data were analyzed using t-test, Mann-Whitney U-test, Kruskal-Wallis test, and Chi-square test as appropriate. RESULTS: In medical students, perceived stress was significantly higher in those in the management quota (both years), living in shared accommodation and from nuclear family (1st year) and male (2nd year). Only accommodation had a statistically significant relationship with perceived stress in 2nd year engineering students. A statistically significant association of perceived stress and anxiety with academic performance was observed. Anxiety in students was significantly more before the examination compared to after the examination. The association of all the coping strategies used, with the academic performance, was statistically significant. CONCLUSIONS: In both medical and engineering students, there was a significant association of perceived stress and anxiety with academic performance. Both medical and engineering students used active coping a little more than avoidant coping strategies during the examination time. The association of all the coping strategies used, with the academic performance, was statistically significant, thereby proving the importance of coping states in academic performance.

Suitable Alternative for Human Cadaver Temporal Bone Dissection: Comparative Micro Ear Anatomy of Cattle, Pig and Sheep with Human.

The study was undertaken to compare the micro ear anatomy of three commonly available animal models which are expected to have similar anatomy to human and to find out suitable model among them as an alternative for human cadaver temporal bone dissection. This is an observational study of comparison of micro ear anatomy of the three animal models with human. Decapitated heads of cattle, pig and sheep were collected from slaughter houses, soft tissues along with brain were removed and preserved in commercially available formalin preservative. CT scan was taken for the three specimens and 3D reconstructions were done. Each specimen was subjected to micro dissection and the anatomical features were studied and compared with human. Among the three animal models sheep is found to be an ideal model for a beginner because of ease of exposure of bone, very thin cortical bone, and no cellularity, good exposure of all the middle ear structures and similar interrelations of middle ear structures with human. Pig may not be an ideal model because of abundant fatty soft tissues, thick periosteum very narrow space occupied by the middle ear, difficulty in accessing cellularity small fragile ossicular chain and overhanging facial nerve.

First successful design of semi-IPN hydrogel-silver nanocomposites: a facile approach for antibacterial application.

Semi-IPN hydrogels in which poly(vinyl pyrrolidone) (PVP) chains were physically dispersed throughout poly(acrylamide) (PAM) gel networks were synthesized. These semi-IPN hydrogel networks can act as excellent nanoreactors for producing and stabilizing metal nanoparticles. The current methodology allows us to entrap metal nanoparticles throughout hydrogel networks via PVP chains. An optimized semi-IPN hydrogel formulation was found to produce silver nanoparticles, ca. 3-5 nm. The synthesized semi-IPN hydrogel-silver nanocomposites were fully characterized by using UV-vis, X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The developed semi-IPN hydrogel-silver nanocomposite (SHSNC) was evaluated for preliminary antibacterial applications.

Long-term effects of Terminalia chebula Retz. on hyperglycemia and associated hyperlipidemia, tissue glycogen content and in vitro release of insulin in streptozotocin induced diabetic rats.

The aqueous extract of the fruits of Terminalia chebula Retz. has been evaluated for its antidiabetic activity in streptozotocin (STZ) induced mild diabetic rats and compared with a known drug, tolbutamide. The oral effective dose (ED) of the extract was observed to be 200 mg/kg body weight, which produced a fall of 55.6% (p<0.01) in the oral glucose tolerance test. Oral administration of ED of aqueous extract of T.chebula (AETC) daily once for two months reduced the elevated blood glucose by 43.2% (p<0.01) and significantly reduced the increase in glycosylated hemoglobin (HbA1c) (p<0.01). The same dose also showed a marked improvement in controlling the elevated blood lipids as well as decreased serum insulin levels in contrast to the untreated diabetic animals. Hepatic and skeletal muscle glycogen content decreased by 75% and 62.9% respectively in diabetic controls, these alterations were partly prevented (34.9% and 21.17%) in AETC treated group when compared to the healthy controls. The in vitro studies with pancreatic islets showed that the insulin release was nearly two times more than that in untreated diabetic animals. The treatment did not have any unfavorable effect on other blood parameters of liver and kidney function tests. LD 50 was found to be above 3 g/kg bw i.e. 15 times of ED, because there were no deaths of animals even at this dose indicating high margin of safety. These findings suggest further investigations for the possible use of the aqueous extract of fruits of T.chebula for the treatment of diabetes.

Oxidoreductases in early gestational monkey placenta during maternal malarial infection: histochemical localisation.

BACKGROUND & OBJECTIVES: Early gestational malaria is more deleterious than late gestational infection. Still the pathophysiology of maternofoetal organ--the placenta in malaria remains almost unexplored during early gestation. Present study dealing with oxidoreductases in early gestational placenta during maternal malarial infection of Plasmodium cynomolgi bastianellii in rhesus monkeys was anticipated to provide a better insight into the functional impairment of this organ leading to foetal abnormalities. METHODS: Three control and four experimental monkeys (Macaca mulatta) were quarantined for one month prior to experimentation. Experimental monkeys at 2- 2 1/2 months of gestation were inoculated with P. cynomolgi bastianellii. On attaining first peak of parasitaemia the placentae were collected from anesthetised animals. The snap-frozen, cryostat sections were subjected to histochemical localisation for 3 (or 17) beta-hydroxysteroid dehydrogenase (beta-HSD) [3 (or 17) beta-hydroxysteroid: NAD (P+) oxidoreductase, EC 1.1.1.51 hydroxysteroid dehydrogenases] and NADPH-tetrazolium reductase [NADPH: (acceptor) oxidoreductase, EC 1.6.99.1 NADPH-TR]. Comparative microscopy of control and malaria infected placental sections was performed and analysed. RESULTS: A localised decrease in both the enzymes was observed in syncytiotrophoblast layer of malaria infected monkey placenta. The areas showing morphological damage of syncytiotrophoblast were also depicting gross reduction in NADPH-TR activity. INTERPRETATION & CONCLUSION: The altered enzymatic activities [3 (or 17) beta-HSD and NADPH-TR] in malaria infected early gestational monkey placenta have been discussed in the light of placental function. It could be concluded by present studies that these alterations would affect the cellular metabolism especially steroidogenesis and detoxification process which in turn would affect the normal development of the foetus as well as maintenance of gestation.

Preliminary studies on antihyperglycemic effect of aqueous extract of Brassica nigra (L.) Koch in streptozotocin induced diabetic rats.

In the streptozotocin induced diabetic rats treated separately with aqueous, ethanol, acetone and chloroform extracts of the seeds of B. nigra, the increase in serum glucose value between 0 and 1 hr of glucose tolerance test (GTT) was the least (29 mg/dl) in aqueous extract treated animals while it was 54, 44 and 44 mg/dl with chloroform, acetone and ethanol extracts respectively. In further studies carried out with aqueous extract, the effective dose was found to be 200 mg/kg body weight in GTT. Administration of 200 mg/kg body weight of aqueous extract to diabetic animals daily once for one month brought down fasting serum glucose (FSG) levels while in the untreated group FSG remained at a higher value. In the treated animals the increase in glycosylated hemoglobin (HbA1c) and serum lipids was much less when compared with the levels in untreated diabetic controls. These findings suggest that further studies with the aqueous extract of B. nigra seeds on its antidiabetic activity would be useful.

Effect of ormeloxifene on ovariectomy-induced bone resorption, osteoclast differentiation and apoptosis and TGF beta-3 expression.

Effect of ormeloxifene, a multifunctional selective estrogen receptor modulator, on prevention of ovariectomy-induced bone resorption in retired breeder female rats, osteoclastogenesis using bone marrow cells from adult Balb/c mice cultured in presence of M-CSF and RANKL, osteoclast apoptosis using terminal deoxynucleotidyl transferase fragment end labeling and TGF beta-3 expression were investigated. Raloxifene, a benzothiophene reported to mimic effects of estrogen in bone, and estradiol were used for comparison. Ormeloxifene (10(-6) and 10(-8)M) significantly inhibited osteoclastogenesis (P<0.001 versus vehicle control) as evidenced by lower number of TRAP-positive osteoclasts in bone marrow cultures and caused apoptosis of osteoclasts. The effect was almost equivalent to that observed in presence of estradiol-17 beta, except that significant number of cells undergoing apoptosis was evident even at 10(-9)M concentration of estradiol-17 beta (P<0.001). Raloxifene, though inhibited osteoclastogenesis at much lower concentrations (10(-8) to 10(-12)M; P<0.001), failed to cause apoptosis of osteoclasts at any of the concentrations used. While ormeloxifene, raloxifene and ethynylestradiol significantly prevented ovariectomy-induced bone loss in vivo in retired breeder female rats, prevention of ovariectomy-induced decrease in BMD and trabecular network of proximal tibia, calcium and phosphorus levels in femur and tibia and prevention of ovariectomy-induced down-regulation of TGF beta-3 expression in lumbar vertebrae was of lower order in raloxifene- than ormeloxifene- or ethynylestradiol-supplemented females. Both the SERMs, however, produced considerable estrogenic effects at the uterine level as evidenced by increase in weight, total and endometrial area and luminal epithelial cell height; the effect being generally greater in raloxifene- than ormeloxifene-treated rats. Findings demonstrate that inhibition of estrogen-deficiency osteoporosis by ormeloxifene, as in case of estradiol, was mediated via inhibition of osteoclastogenesis, apoptosis of osteoclasts and up-regulation of TGF beta-3 expression. Raloxifene, though effective in inhibiting osteoclastogenesis in vitro at much lower concentrations, was not only less potent in preventing ovariectomy-induced bone loss in retired breeder female rats in vivo but also appeared to have a different mechanism of action than ormeloxifene and estradiol.

Distribution of lovastatin to bone and its effect on bone turnover in rats.

Statins, the widely used lipid-lowering drugs, are inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, which catalyses a rate-limiting step in the biosynthesis of cholesterol. Many previous reports show that statins can act both as bone anabolic and as anti-resorptive agents but their beneficial effects on bone turnover are still controversial. Considering their high liver specificity and low oral bioavailability, the distribution of statins to the bone microenvironment is questionable. In this study, the distribution of lovastatin and its active metabolites to bone, with respect to plasma and liver compartments, was examined after oral and intravenous administration in female rats. As compared with oral administration, the distribution of lovastatin to the bone compartment was significantly enhanced after intravenous administration. Further, the effect of lovastatin on bone turnover was studied in-vitro and in-vivo to assess its anti-osteoporotic potential. Lovastatin acid but not lovastatin was found to inhibit parathyroid-hormone-induced bone resorption in an in-vitro chick embryo bone assay. Oral, as well as intravenous, short-term lovastatin treatment significantly reduced the serum total cholesterol, serum total alkaline phosphatase and urinary crosslinks in ovariectomized rats. In accordance with its increased distribution to the bone compartment, intravenously administered lovastatin was more effective in reducing the ovariectomy-induced increase in markers of bone metabolism, especially urinary crosslinks. The findings of this study suggest that statins inhibit bone resorption and that their anti-resorptive efficacy can be increased by administering them by routes other than oral so as to achieve their enhanced concentration in bone.