Enhancing bone repair through improved angiogenesis and osteogenesis using mesoporous silica nanoparticle-loaded Konjac glucomannan-based interpenetrating network scaffolds.

We have fabricated and characterized novel bioactive nanocomposite interpenetrating polymer network (IPN) scaffolds to treat bone defects by loading mesoporous silica nanoparticles (MSNs) into blends of Konjac glucomannan, polyvinyl alcohol, and polycaprolactone. By loading MSNs, we developed a porous nanocomposite scaffold with mechanical strengths comparable to cancellous bone. In vitro cell culture studies proved the cytocompatibility of the nanocomposite scaffolds. RT-PCR studies confirmed that these scaffolds significantly upregulated major osteogenic markers. The in vivo chick chorioallantoic membrane (CAM) assay confirmed the proangiogenic activity of the nanocomposite IPN scaffolds. In vivo studies were performed using Wistar rats to evaluate the scaffolds' compatibility, osteogenic activity, and proangiogenic properties. Liver and renal function tests confirmed that these scaffolds were nontoxic. X-ray and µ-CT results show that the bone defects treated with the nanocomposite scaffolds healed at a much faster rate compared to the untreated control and those treated with IPN scaffolds. H&E and Masson's trichrome staining showed angiogenesis near the newly formed bone and the presence of early-stage connective tissues, fibroblasts, and osteoblasts in the defect region at 8 weeks after surgery. Hence, these advantageous physicochemical and biological properties confirm that the nanocomposite IPN scaffolds are ideal for treating bone defects.

Chlorhexidine: a retrospective observational study of a potentially life-threatening molecule

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Comparison of two impression techniques for auricular prosthesis: pilot study.

The purpose of this article was to compare the accuracy of a new impression technique, the triple-layer impression technique (TLIT), with the conventional impression technique (CIT) to fabricate an auricular prosthesis. Fifteen male subjects (aged 22-45 yr) were selected. Ten markings were made on the subject's ear (super aurale [sa], sub aurale [sba], pre aurale [pra], post aurale [poa], A, A1, B, B1, C, and C1) and five measurements (sa-sba, pra-poa, A-A1, B-B1, and C-C1) were made. Custom-made trays were used to record impression in CIT and TLIT. Impressions were made using alginate, and models were cast with type IV gypsum product. Markings were transferred on the cast. Measurements were rechecked on the models. Distribution analysis of difference in measurements between the two impression techniques and the subject's actual values was evaluated. Sign test was used to analyze the statistical significance. Statistically significant differences were found in measurements A-A1, B-B1, and C-C1 between the two techniques when compared with the subject's actual dimensions (p < 0.01). TLIT was found to produce accurate models when compared with CIT. The TLIT used in the study was cost effective, less technique sensitive, and tailor made to reduce chairside orientation time during wax try-in appointments for rehabilitating patients, especially those with unilateral auricular defects.

Multiple approaches to evaluate the toxicity of the biomass fuel cow dung (kanda) smoke.

Cow dung (Kanda) is a major source of energy in rural and urban population of developing countries and is burnt in traditional open stoves in confined space of kitchen without proper ventilation. In epidemiological studies, biomass fuel smoke has been reported to be responsible for several respiratory disorders in exposed population. In a laboratory experiment, female wistar rats were exposed to kanda smoke for 60 min/day over a period of 12 weeks. Chemical analysis of smoke showed the presence of PAHs. The increase in CYP1A1, GST-ya, GST-yc expression was found in 12 week exposed lung tissues as compared with controls. The exposure to smoke resulted in significant alteration in the BALF cells in the form of clustering of alveolar macrophages and giant cell formation with vacuolated cytoplasm. The macrophages also showed thickness and villi like projections on the cell surface thus reducing their phagocytic activities. Histopathological changes in lung tissue were manifested in the form of damage to bronchiolar epithelium, edema and thickening of alveolar septa and emphysema after 4 and 8 week of exposure. These findings suggest that exposure to kanda smoke increases pulmonary tissue damage and may result in various forms of respiratory infections in the exposed popultion.

Effect of fly ash inhalation on biochemical and histomorphological changes in rat liver.

The effect of fly ash inhalation (4h daily, 5 days a week) for 28 days on the deposition of metal ions and histopathological changes in the liver and serum clinical enzymes has been studied. The results showed an increase in the concentration of metals such as cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), and lead (Pb) in the tissues of exposed rats. The level of metals varied from metal to metal and from organ to organ. Level of serum enzymes such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, and alkaline phosphatase were increased in fly ash exposed rats using whole body inhalation exposure as compared to sham controls. Histopathological studies of rat liver exposed to fly ash revealed infiltration of mononuclear cells in and around the portal triads, which seems to be laden with fly ash particles. Hepatocytes showed necrotic changes such as pyknotic nuclei, karyorrhexis, and karyolytic. These changes were more towards the centrolobular areas than the midzonal and periportal areas. These findings demonstrate that the toxic metals of inhaled fly ash in rats may get translocated into extrapulmonary organs, become deposited and hence may manifest their toxic effects on different tissues.

Hepatotoxic alterations induced by subchronic exposure of rats to formulated fenvalerate (20% EC) by nose only inhalation.

OBJECTIVE: Fenvalerate (20% EC) is a synthetic pyrethroid, which is commonly used in India by farmers for the protection of many food and vegetable crops against a wide variety of insects. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation exposure was carried out to investigate the hepatotoxic effects. METHOD: Adult male rats were exposed to fen for 4 h/day, 5 days a week for 90 days by using Flow Past Nose Only Inhalation Chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. RESULTS: The results indicated hepatomegaly, increased activities of serum clinical enzymes (indicative of liver damage/dysfunction) along with pronounced histopathological damage of liver. CONCLUSION: The hepatotoxic potential of formulated Fen (20% EC) in rats exposed by nose only inhalation is being reported for the first time and warrant adequate safety measures for human beings exposed to this insecticide, particularly by inhalation route.

Effect of fly ash inhalation on biochemical and histomorphological changes in rat lungs.

Effect of respirable fly ash particles inhalation on lungs of rats was investigated by exposing them to respirable aerosols of size classified power plant fly ash at average concentrations of up to 14.4 +/- 1.77 mg/m3 for 4 hr/day for 28 consecutive days. A remarkable increase was found in blood eosinophil counts of fly ash exposed animals. Biochemical indicators of pulmonary damage viz. lactate dehydrogenase (cytoplasmic enzyme used as a measure of cell injury), gamma-glutamyl transferase (Clara cell damage) and alkaline phosphatase (potential measure of Type 11 cell secretions) in broncho alveolar lavage fluid (BALF) of fly ash exposed group showed significant elevation. Clumping of fly ash particles in the lungs was observed as evidenced by fly ash ladened macrophage accumulation in the alveolar region. The results suggest a damage, local inflammation and remodelling of lung as indicated by hypertrophy and hyperplasia. These changes reflect the toxic effects of the fly ash inhalation.

Hypocholesterolemic effect of spirulina in patients with hyperlipidemic nephrotic syndrome.

In nephrotic syndrome, large amounts of plasma proteins are lost in urine, causing a decrease in the plasma oncotic pressure. This leads to enhanced hepatic synthesis of albumin and other proteins, including lipoproteins, causing a secondary hyperlipidemia. Essential fatty acids such as gamma-linolenic acid (GLA) can prevent accumulation of cholesterol in the body, and spirulina has an appreciable amount of GLA. In this study 23 patients (age 2 to 13 years) with nephrotic syndrome received either medication (group I) or medication plus 1 g/day Spirulina (group II). Height, weight, and serum levels of fasting blood sugar, triglycerides, total cholesterol (TC), and low- and high-density cholesterol fractions (LDL-C and HDL-C, respectively) were measured before and after the 2-month study period. Mean height and weight were normal compared with healthy, age-matched Indian children. Lipoprotein cholesterol levels were significantly increased at baseline. TC significantly decreased by 116.33 mg/dl, LDL-C by 94.14 mg/dl, and triglycerides by 67.72 mg/dl in group II; in control group I, these values fell by 69.87, 61.13, and 22.62 mg/dl, respectively. The LDL-C:HDL-C ratio also decreased significantly, by 1.66 in group II and 1.13 in group I. TC:HDL-C decreased by 1.96 in group II and 1.19 in group I. HDL-C:LDL-C also improved significantly in both the groups. It can be concluded that spray-dried Spirulina capsules, rich in antioxidants, GLA, amino acids, and fatty acids, helped reduce the increased levels of lipids in patients with hyperlipidemic nephrotic syndrome.

Silica induced early fibrogenic reaction in lung of mice ameliorated by Nyctanthes arbortristis extract.

OBJECTIVE: To investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles. METHOD: Lung injury was induced in Swiss mice through inhalation exposure to silica particles (< 5 mu) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury. RESULTS: Inhalation of silica increased the level of tumor necrosis factor-alpha (TNF-alpha), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-alpha in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung. CONCLUSION: NAT leaf extract helps in bypassing silica induced initial lung injury in mice.

Effect of trichloroethylene (TCE) inhalation on biotransformation enzymes of rat lung and liver.

Trichloroethylene (TCE) is widely used as an industrial solvent and cleaning fluid. In the present study the toxic effects of TCE inhalation on pulmonary and hepatic biotransformation enzymes in rats have been investigated by assay of aniline hydroxylase (AH), aminopyrine-N-demethylase (APD), benzo-a-pyrene hydroxylase (BH) and glutathione-s-transferase (GST) activities and glutathione (GSH) contents in liver as well as lungs of exposed animals. In both organs phase I and phase II drug metabolizing enzymes have been found to be increased along with decrease in GSH contents following TCE inhalation. Pulmonary as well as hepatic MFO's seem to be activated by inhaled TCE probably in an attempt for its rapid detoxification and reduced glutathione is used during its biotransformation.

Steroidogenic alterations in testes and sera of rats exposed to formulated Fenvalerate by inhalation.

Fenvalerate (Fen) is a synthetic pyrethroid, which is commonly used for destroying a variety of insect pests damaging several vegetable, fruit, and cotton crops. This insecticide is also used to mitigate household insects like flies, cockroaches, mosquitoes, and so forth. Human beings are exposed to formulated Fen preparations mostly by inhalation during spraying in fields for crop protection, for control of household insects, and also during handling and packaging at manufacturing plants. Limited online information is available regarding toxic effects of formulated Fen exposure on mammalian reproductive system. The present study has been undertaken to investigate male reproductive toxic effects of a formulated preparation of Fen (20% EC) particularly in relation to steroidogenic alterations in testes and sera of rats exposed by nose-only inhalation for (4 hours/day and five days a week) for three months. The results indicate significant reduction in the weight of testes, epididymal sperm counts, and sperm motility, along with decrease in marker testicular enzymes for testosterone biosynthesis viz. 17-beta-hydroxy steroid dehydrogenase (17-beta-HSD) and glucose-6-phosphate dehydrogenase (G6PDH), leading to net decrease in serum testosterone concentration in group of rats exposed to one-fifth LC50 of Fen (20% EC) by inhalation (4 hours/day, five days a week) subchronically for three months. These results for the first time indicate the role of testosterone in Fen (20% EC)-induced male reproductive toxicity of rats subchronically exposed by inhalation probably due to neuroendocrine-mediated phenomenon and hormone-disrupting property of the insecticide.

Normal and abnormal heme biosynthesis. 3.(1)Synthesis and metabolism of tripropionate analogues of coproporphyrinogen-III: novel probes for the active site of coproporphyrinogen oxidase.

Coproporphyrinogen oxidase (copro'gen oxidase) catalyses the oxidative decarboxylation of two propionate side chains on coproporphyrinogen-III to produce protoporphyrinogen-IX. This process is very poorly understood at a molecular level, and copro'gen oxidase remains one of the least well-characterized enzymes in the heme biosynthetic pathway. To provide a rigorous test for a proposed model for substrate recognition and binding by this enzyme, two tripropionate analogues of copro'gen-III were prepared where an ethyl group replaced one of the usual propionate residues on positions 13 or 17. Although the required substrate probes are porphyrinogens (hexahydroporphyrins), the corresponding porphyrin methyl esters were initially synthesized via tripyrrene and a,c-biladiene intermediates. These were hydrolyzed and reduced with 3% sodium-amalgam to give the unstable porphyrinogens needed for the biochemical investigations. The modified structure with a 13-ethyl moiety was metabolized by avian preparations of copro'gen oxidase to give a monovinylic product, but the isomeric 17-ethylporphyrinogen afforded a divinylic product, albeit with poorer overall conversion. These results strongly support the proposed model for substrate binding at the active site of copro'gen oxidase.

A study report of 174 units of placental umbilical cord whole blood transfusion in 62 patients as a rich source of fetal hemoglobin supply in different indications of blood transfusion.

BACKGROUND: In the animal kingdom, even herbivorous animals swallow the placenta after the birth of the baby (for example, the cow). In the human system, we do not know about the proper utilization of the placenta and membranes although there are suggestions regarding this on the basis of research on placental umbilical cord blood stem cells as an alternative to bone marrow transplantation. In this present series of placental umbilical cord whole blood transfusions, we wanted to examine the safety aspect of other components of cord blood transfusion, e.g., fetal RBC, growth factors and cytokine filled plasma, etc., in different indications of blood transfusion, from the pediatric to the geriatric age group, in malignant and non-malignant disorders affecting our patients. METHODS: One hundred and seventy-four units of umbilical cord whole blood were collected aseptically from the umbilical vein after caesarean section in standard pediatric blood transfusion bags, after the removal of the baby from the operative field and after confirming the stable condition of the mother. The volume of cord blood varied from 50 ml to 140 ml with a mean of 86 ml+/-16 ml. RESULTS AND ANALYSIS: The cord blood was transfused immediately (within three days of collection) to 62 patients from nine years to 78 years of age, of whom 32 were suffering from varying stages and grades of malignancy from 1 April 1999 till date i.e., 11 Aug 2000, after obtaining adequate consent and following the precautions of standard blood transfusion protocol. The remaining 30 patients included patients suffering from thalassemia major, aplastic anemia, systemic lupus erythematosus, chronic renal failure, rheumatoid arthritis, ankylosing spondylitis and a geriatric group of patients with benign prostatic hypertrophy. All have tolerated the procedure without any immunological or non-immunological reactions. CONCLUSION: On the basis of our experience with 174 units of placental umbilical cord whole blood transfusion in malignant and non-malignant conditions (within three days of collection and preservation at 1-6 degrees C in a refrigerator), we are of the opinion that this is a safe transfusion protocol which takes advantage of the safety of nature's finest biological sieve, i.e., the placenta, as an alternative to adult whole blood transfusion. It also has the advantage of a higher oxygen carrying capacity of fetal hemoglobin in addition to many growth factors and other cytokine filled cord blood plasma along with its hypoantigenicity.

Pulmonary toxicity of a formulated preparation of fenvalerate in rats subchronically exposed by nose only inhalation for 90 days.

OBJECTIVE: The pulmonary toxicity of a commercially available formulated preparation of Fenvalerate (Fen), a synthetic pyrethroid has been studied in rats following subchronic nose only inhalation exposure route. METHOD: Adult male rats were exposed to Fen for 4 h/day, 5 days a week for 90 days by using Flow Past Dynamic Nose only Inhalation Chamber. RESULTS: Fen exposed rats showed a significant increase in enzymatic activities of lactate dehydrogenase (LDH), acid phosphatase (ACP), alkaline phosphatase (ALP) and gamma-glutamyl transferase (gamma-GT) which are considered as biochemical indicators of pulmonary damage. The concomitant histopathological examination of Fen exposed rats' lung revealed inflammatory changes viz., influx of mononuclear cells admixed with a few giant cells in alveolar lumen, hypetrophied bronchiolar and alveolar epithelial lining cells and presence of edematous fluid in alveolar lumen alongwith congested parenchymatous blood vessels. CONCLUSION: These results for the first time indicate the pulmonary toxic effects of a commonly used formulated Fen preparation by using rat model and nose only inhalation as the route of exposure.

Hepatoxic alterations induced by inhalation of trichlorethylene (TCE) in rats.

OBJECTIVE: Trichlorethylene (TCE) is one of the most potent organic unsaturated solvents being used in dry cleaning, metal degreasing, thinner for paints varnishes and electroplating, etc. and has been reported to be a hepatoxicant through oral and dermal exposure. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation toxicity study was carried out for hepatotoxic studies. METHODS: Inhalation toxicity studies was carried out by exposing rats to TCE for 8, 12 and 24 weeks in a dynamically operated whole body inhalation chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. RESULTS: Significant increase in liver weight (liver enlargement) appeArance of necrotic lesion with fatty changes and marked necrosis were observed after longer duration (12 and 24 weeks) of TCE exposure. The lysosomal rupture resulted in increased activity of acid and alkaline phosphatase alongwith reduced glutathione content and total increased sulfhydryl content in liver tissue. CONCLUSION: TCE exposure. through inhalation route induces hepatotoxicity in terms of marked necrosis with fatty changes and by modulating the lysosomal enzymes.

Trichloroethylene induced testicular toxicity in rats exposed by inhalation.

Trichloroethylene (TCE) is an organic solvent used in dry cleaning, metal degreasing, thinner for paints and varnishes, anesthetic agent, and so forth. Human beings are appreciably exposed to TCE vapours by inhalation route. The present study has been undertaken to investigate whether TCE inhalation may also bring about testicular toxic effects. Our results indicate that inhalation of TCE by male rats for 12 and 24 weeks brings about significant reduction in absolute testicular weight, and alters marker testicular enzymes activity associated with spermatogenesis and germ cell maturation, along with marked histopathological changes showing depletion of germs cells and spermatogenic arrest.

Structure-activity relationships of a novel class of Src SH2 inhibitors.

The structure-activity relationships (SAR) of a novel class of Src SH2 inhibitors are described. Variation at the pY+1 and pY+3 side chain positions using 2,4- and 2,5-substituted thiazoles and 1,2,4-oxadiazoles as scaffolds resulted in inhibitors that bound as well as the standard tetrapeptide Ac-pYEEI-NH2.