Composite 3D printing of biomimetic human teeth.

Human teeth are mechanically robust through a complex structural composite organisation of materials and morphology. Efforts to replicate mechanical function in artificial teeth (typodont teeth), such as in dental training applications, attempt to replicate the structure and morphology of real teeth but lack tactile similarities during mechanical cutting of the teeth. In this study, biomimetic typodont teeth, with morphology derived from X-ray microtomography scans of extracted teeth, were 3D printed using an approach to develop novel composites. These composites with a range of glass, hydroxyapatite and porcelain reinforcements within a methacrylate-based photopolymer resin were compared to six commercial artificial typodont teeth. Mechanical performance of the extracted human teeth and 3D printed typodont teeth were evaluated using a haptic approach of measuring applied cutting forces. Results indicate 3D printed typodont teeth replicating enamel and dentine can be mechanically comparable to extracted human teeth despite the material compositions differing from the materials found in human teeth. A multiple parameter variable of material elastic modulus and hardness is shown to describe the haptic response when cutting through both human and biomimetic, highlighting a critical dependence between the ratio of material mechanical properties and not absolute material properties in determining tooth mechanical performance under the action of cutting forces.

Docking studies for screening anticancer compounds of Azadirachta indica using Saccharomyces cerevisiae as model system.

INTRODUCTION: Plants have a long history of use in the treatment of cancer. Plant-derived compounds have played an important role in the development of several clinically useful anticancer agents. In the recent years, more emphasis has been placed on identifying plant-derived compounds that can be used as an effective treatment for life-threatening diseases such as cancer. Cancer is a disease where there is abnormal cell proliferation. The proliferation of the cancer cells are restrained by cdk/cyclin complexes, which control the normal process of cell cycle. MATERIALS AND METHOD: The current study involves the investigation of the anticancer property of the chemical compounds present in the leaves of Azadirachta indica by performing docking studies with the cell cycle control protein using Arguslab. RESULT: The compounds were docked with the cdk1 protein to identify suitable inhibitors against the protein function. CONCLUSION: The study were conducted on yeast Cdk protein, because these proteins showed homology with the human Cdks.

Antioxidant activities of bark extract from mangroves, Bruguiera cylindrica (L.) Blume and Ceriops decandra Perr.

OBJECTIVES: The antioxidant activities of two Indian mangrove plants, Bruguiera cylindrica and Ceriops decandra, were investigated. MATERIALS AND METHODS: Total phenolics and total flavonoid contents of the mangroves were determined using folin-ciocalteu reagent method and aluminium chloride method, respectively. Antioxidant capacity was assessed by the following methods: 1,1-diphenyl-2-picryl hydroxyl (DPPH.) quenching assay; 2,2'- azinobis-3-ethylbenzothiozoline-6-sulfonic acid (ABTS.(+)) cation decolorization test; scavenging capacity towards hydroxyl ion radicals (.OH); reductive capacity; and antihemolytic activity. RESULTS: The mangroves yielded 233.3 ± 0.062 and 283.31 ± 0.04 mg gallic acid equivalent/g phenolic contents and 11.6 ± 0.12 and 15.1 ± 0.02 mg quercetin equivalent/g flavonoid contents. The methanol extracts of both mangroves exhibited high antiradical activity against DPPH., ABTS.(+), and .OH radicals. The reductive capacity of the extracts increased with increasing concentration of samples. The extracts also inhibited H(2)O(2) induced hemolysis in cow blood erythrocytes. The antioxidant activities were found stronger than that of the reference standard, butylated hydroxy toluene (BHT). The antioxidant activity of mangrove plants was correlated with total phenolics and flavonoid contents. CONCLUSION: Both plants can be considered as good sources of natural antioxidants for medicinal uses. Further studies are necessary to isolate active principles responsible for the overall antioxidant activity of the extracts.

Measurement of hemodynamic and anatomic parameters in a swine arteriovenous fistula model.

PURPOSE: Although arteriovenous fistulae (AVFs) are currently the preferred mode of permanent hemodialysis access they do have significant problems due to initial non-maturation and a later venous stenosis. These problems appear to have been exacerbated following a push to increase AVF prevalence in the US. The reasons for both AVF non-maturation and the later venous stenoses are unclear but are thought to be related to abnormal hemodynamic wall shear stress (WSS) profiles. This technical note aims to describe the successful development of measurement techniques that can be used to establish a complete hemodynamic profile in a pig model with two different configurations of AVF. METHODS AND RESULTS: The curved and straight AVF configurations were created in an in vivo pig model. Flow and pressure in the AVFs were measured using the perivascular flow probes and Doppler flow wires while the pressure was recorded using a pressure transducer. The anatomical configuration was obtained using two different approaches: a) combination of intravascular ultrasound (IVUS) and angiograms, (b) 64 slice CT angiography. 3D models were reconstructed using image processing and computer modeling techniques. Numerical calculations were then performed by applying the measured flow and pressure data into the configurations to obtain the hemodynamic WSS profiles. CONCLUSION: The described methodologies will allow the calculation and optimization of WSS profiles in animal models. This information could then be translated to the clinical setting where it would have a positive impact on improving the early maturation rates of AVFs as well as reducing the late venous stenoses.

Identification of novel Cry1Ac binding proteins in midgut membranes from Heliothis virescens using proteomic analyses.

Proteins such as aminopeptidases and alkaline phosphatases, both glycosyl-phosphatidyl-inositol (GPI) anchored proteins, were previously identified as Cry1Ac binding proteins in the Heliothis virescens midgut. To identify additional toxin binding proteins, brush border membrane vesicles from H. virescens larvae were treated with phosphatidyl inositol phospholipase C, and released proteins were resolved by two-dimensional electrophoresis. Protein spots selected by their ability to bind Cry1Ac were identified by MALDI-TOF mass spectrometry coupled to peptide mass fingerprinting (PMF) and database searching. As in previous studies, H. virescens alkaline phosphatase was identified as a Cry1Ac binding protein. V-ATP synthase subunit A and actin were identified as novel Cry1Ac binding proteins in H. virescens. Additional toxin-binding proteins were predicted based on MS/MS fragmentation and de novo sequencing, providing amino acid sequences that were used in database searches to identify a phosphatase and a putative protein of the cadherin superfamily as additional Cry1Ac binding proteins.

In vitro paclitaxel and radiation effects on the cell types responsible for vascular stenosis: a preliminary analysis.

Hemodialysis vascular access dysfunction as a result of venous neointimal hyperplasia in dialysis access grafts and fistulae is currently a huge clinical problem. The aim of this study was to assess the effects of paclitaxel and radiation, both singly and in combination on the proliferation of cell types present within the lesion of venous neointimal hyperplasia (vascular smooth muscle cells, fibroblasts and endothelial cells within the neointimal microvessels). Vascular smooth muscle cells, fibroblasts and endothelial cells were plated onto 96-well plates and exposed to different concentrations and doses of paclitaxel and radiation, respectively (both individually and in combination). Growth inhibition was assessed with an MTT assay. Both paclitaxel and radiation resulted in significant growth inhibition of all three cell types. However, even small doses of paclitaxel appeared to attenuate the antiproliferative effect of radiation on these cell types. Further experiments to elucidate the mechanism behind these findings could result in a better understanding of combination antiproliferative therapies.

Adenovirus-mediated p53 gene therapy in osteosarcoma cell lines: sensitization to cisplatin and doxorubicin.

The poor prognosis for patients with metastatic osteosarcoma (OS) indicates that new therapeutic options should be explored. Studies with adenoviral-mediated p53 gene transfer have been conducted in many cancer types including cervical, ovarian, prostatic and head and neck tumors. However, limited work has been carried out with pediatric cancers, including OS. Using three viral constructs containing cDNA for wild-type p53, mutant p53 (Cys135Ser) and lacZ, we studied the effect of adenoviral-mediated gene therapy in four OS cell lines: Saos-2 (p53-/-), HOS (R156P), KHOS/NP (R156P) and MNNG (R156P, F270L). We demonstrated that the virus efficiently enters the cells using the beta-galactosidase assay. Using the MTT assay, we have shown a dose-dependent decrease in cell viability 72 h post-treatment that occurs with Ad-wtp53 but not with Ad-mutp53. We have also shown that treatment with Ad-wtp53 significantly increases sensitivity of the cell lines to cisplatin and doxorubicin, chemotherapeutic agents commonly used in the treatment of OS. Our results indicate that restoration of wt p53 function in OS cells provides a basis for novel approaches to treatment of this disease.

Evaluation of the aneugenic potential of the fungicide Ferbam in mice.

Ferbam, a potent dithiocarbamate fungicide is used as a protectant against a wide variety of fungal diseases in fruits, vegetables, and ornamental plants. The wide-spread use of this chemical is likely to pollute the environment. Hence, it was planned to test the possible genotoxicity of Ferbam through its aneugenic potential in the in vivo mouse (Mus musculus) test system. Four different doses of Ferbam, namely, 7.5, 15.0, 30.0, 60.0 mg/kg body weight were administered orally to mice Mus musculus suspended in gum tragacanth representing, respectively, 1/16, 1/8, 1/4;, 1/2 th of the LD50 value. They were sacrificed at 6-, 12-, 24-, and 48-h intervals along with a distilled water negative control at 2 mg/kg body weight. Colchicine treated animals were used as positive controls. Bone marrow preparations were made following the standard Hypotonic flame dry Giemsa staining technique to study the dose and time yield effect of Ferbam. The aneugenic potential was evaluated for C-mitotic effects by scoring the mitotic index, c-mitoses frequency, anaphase reduction, and hyper/hypodiploidy induction. Ferbam showed a significant increase in the mitotic index and C-mitoses effects and anaphase decreased at the highest doses of 30 and 60 mg/kg at 12- and 24-h intervals. Colchicine induced significant effects in all the aneugenic parameters observed at all the time intervals. There was no significant induction of either hyperdiploidy or hypodiploidy by Ferbam, unlike colchicine, indicating that the fungicide Ferbam is not aneugenic in the mouse test system.

Behavioural and biochemical changes after simultaneous and post-treatment of vitamin A and D on cadmium toxicity.

In the present study, an investigation was undertaken to assess the protective efficacy in cadmium toxicity of vitamins administered simultaneously as well as post-treatment. Rats were treated with cadmium 1 mg/kg body weight (bw) powdered vitamin A chewable tablet 500 IU/kg bw/day and injectable vitamin D(3) (made into a suspension with gum tragacanth in 100 ml distilled water) 100 IU/kg bw/day, mixed with powdered pellet feed and fed to experimental animals. Spontaneous motor activity and Rota Rod Endurance time was recorded after both simultaneous (for 21 days) and post-treatment (42 days). Vitamin treated animals by themselves behaved like controls but attenuated the cadmium effect when given Cd simultaneously or as post-treatment. While the biochemical changes were assayed, vitamins which did not have any influence on their own, given simultaneously and as post-treatment, antagonized the cadmium effect on heart, liver tissues and serum. Both simultaneous and post-cadmium and -vitamin treatments significantly increased the activities of the enzymes aspartic amino transferase, alanine aminotransferase, acid phosphatase and alkaline phosphatase in tissues and serum. Simultaneous and post-vitamin treatment with Cd had an effect of bringing back the activity of the enzymes closer to control values. These data suggest that treatment with vitamin A and D can minimise the Cd effect when given to the population exposed to Cd.

Neural techniques for combinatorial optimization with applications.

After more than a decade of research, there now exist several neural-network techniques for solving NP-hard combinatorial optimization problems. Hopfield networks and self-organizing maps are the two main categories into which most of the approaches can be divided. Criticism of these approaches includes the tendency of the Hopfield network to produce infeasible solutions, and the lack of generalizability of the self-organizing approaches (being only applicable to Euclidean problems). This paper proposes two new techniques which have overcome these pitfalls: a Hopfield network which enables feasibility of the solutions to be ensured and improved solution quality through escape from local minima, and a self-organizing neural network which generalizes to solve a broad class of combinatorial optimization problems. Two sample practical optimization problems from Australian industry are then used to test the performances of the neural techniques against more traditional heuristic solutions.

Long-term follow-up of patients treated with ileoendorectal pull-through and right colon onlay patch for total colonic aganglionosis.

BACKGROUND/PURPOSE: This study was performed to assess the long-term follow-up of five patients who underwent one-stage ileoendorectal pull-through with right colon onlay patch for total colonic aganglionosis (TCA) at Kaiser Permanente Medical Center. METHODS: A retrospective review of inpatient and outpatient charts and telephone follow-up of all patients were conducted to obtain current data regarding growth, development, bowel function, and postoperative and late complications. RESULTS: Follow-up has ranged from 2 to 11 years. All patients are at or above the 50th percentile for weight by age and are continent with 1 to 5 daily bowel movements. Only two patients required reoperation. A perirectal abscess developed in one patient 2 months postoperatively. In the second patient a functional obstruction was relieved by sphincterotomy. CONCLUSIONS: Ileoendorectal pull-through with right colon onlay patch is associated with few early and late postoperative complications; it appears to be superior to other procedures in the early postoperative period because of the more rapid return to acceptable stooling patterns. This method of reconstruction provides an excellent opportunity for normal growth, development, and long-term bowel function.

Sentinel lymphadenectomy for breast cancer in a community managed care setting.

PURPOSE: To evaluate the feasibility, accuracy, and reproducibility of intraoperative lymphatic mapping and sentinel lymphadenectomy (IOLM/SL) in the staging of breast cancer patients in a community managed care setting. PATIENTS AND METHODS: One hundred forty-five patients with primary breast cancer were prospectively studied over a 26-month period. They underwent vital dye injection at their primary breast cancer site. Lymphatic channels were traced to the sentinel lymph node, which was excised, serially sectioned, and examined. A level I and II axillary lymph node dissection and definitive breast surgery were then performed. RESULTS: Sentinel nodes were identified in 103 of 145 procedures (71.0%). Sentinel and nonsentinel lymph nodes were concordant in 100 of 103 cases (97.1%). Three patients (9.7%) had falsely negative sentinel nodes; there were none in the last 80 patients. Of 28 positive sentinel nodes, 12 (42.9%) represented the only tumor-containing node within the axilla. Sentinel nodes were significantly more likely to contain tumor than nonsentinel nodes (33/50, 66.0% vs 54/467, 11.6%, P < 0.0001). IOLM/SL identified more micrometastases (< 2 mm) than standard axillary lymph node dissection (13/33, 39.6% vs 4/177, 2.2%, P < 0.001). Nine of 42 patients (21.4%) whose sentinel node could not be identified had five or more nodal metastases. Two of six patients with presumed Tis primaries had nodal metastases. DISCUSSION: IOLM/SL accurately identifies the sentinel lymph node(s) most likely to contain metastatic disease. A procedural learning curve was present. An unsuccessful IOLM/SL was a risk factor for considerable nodal metastases. IOLM/SL with a tumor-free sentinel node may obviate a formal axillary lymph node dissection. The technique was feasible, economical, and reproducible within the context of a community managed care facility, while not placing exacting demands on operating room, pathology, or nuclear medicine personnel.

Simultaneous correction of malrotation and gastroesophageal reflux in infants.

Gastroesophageal reflux (GER) is often associated with gastrointestinal malrotation in infants. Primary correction of the malrotation, reserving a secondary antireflux procedure for those patients with persistent symptoms of GER, is most commonly practiced. This decision is based on the notion that an antireflux procedure may be unnecessary and is associated with added morbidity. We retrospectively reviewed 12 infants with GER and malrotation. All infants had symptoms attributed to GER and/or malrotation. A control group of seven infants with malrotation only was included for comparison of operative duration and postoperative recovery. Infants who received concurrent Ladd and Nissen procedures (Group 1, n=8) had immediate resolution of symptoms. Infants treated by Ladd procedure alone (Group 2, n=4), had persistent symptoms, despite postoperative medical therapy. A subsequent antireflux procedure was necessary. Comparison of operative times showed that a simultaneous procedure added, on average, 35 minutes to the Ladd procedure. Postoperative feeding and hospital stay were comparable between Group 1 and the control group. In contrast, Group 2 patients had longer hospitalizations due to ineffective medical therapy for persistent GER. No significant morbidity was noted. We recommend comprehensive surgical treatment with concurrent Ladd and Nissen procedures. This approach provides expedient and effective treatment of GER and malrotation, with minimal increase in operative time and no increase in morbidity .

Congenital bronchobiliary fistula: diagnosis and postoperative surveillance with HIDA scan.

Congenital bronchobiliary fistula (CBBF) is an extremely rare anomaly with myriad presentations that often include common bile duct abnormalities. Traditionally, bronchoscopy and bronchography have been used to establish the diagnosis. A full-term neonate with pneumonia and bilious secretions was diagnosed as having CBBF by means of a HIDA scan. Successful repair consisted of a right thoracotomy, high ligation of the fistula via an extrapleural approach, and cholecystography to confirm biliary drainage into the duodenum. The HIDA scan is a safe and efficient means to diagnose CBBF. When used in combination with surgical contrast studies, it provides clear delineation of all variations of this abnormality, enabling one-stage correction.

A comparison of the hemodynamic and ventilatory effects of abdominal insufflation with helium and carbon dioxide in young swine.

Abdominal CO2 insufflation has been shown to cause hypercarbia, acidemia, and decreased oxygenation in a pediatric animal model. Such metabolic derangements have prompted a search for alternative insufflation gases. This study compares the hemodynamic and ventilatory changes that occur during pneumoperitoneum with CO2 and helium. Four juvenile swine were intubated and given general anesthesia. Minute ventilation was adjusted to obtain a baseline Pco2 of between 32 and 36 mm Hg, and was kept constant for the duration of the experiment. The subjects initially were insufflated with CO2 or helium at a pressure of 10 mm Hg. Peak ventilatory pressure, end-tidal CO2 (ETCO2) arterial pH, Pco2, Po2, and right atrial and inferior vena caval pressures were measured before and during a 1-hour insufflation period. After desufflation, Pco2 and pH were restabilized. The same parameters were then measured during reinsufflation with the alternate gas. CO2 insufflation caused significant decreases in pH, from 7.51 +/- 0.03 to 7.32 +/- 0.06, and Po2 increased from 261 +/- 49 to 189 +/- 33 mm Hg. Pco2 increased from 35.0 +/- 1.4 to 57.9 +/- 6.3 mm Hg. ETCO2 also increased, from 29.0 +/- 2.2 to 47.2 +/- 5.0 mm Hg. Helium insufflation caused pH to decrease from 7.51 +/- 0.01 to 7.42 +/- 0.04. Pco2 increased from 32.8 +/- 0.8 to 43.5 +/- 3.9 mm Hg, and ETCO2 increased from 27.8 +/- 0.5 to 36.8 +/- 3.1 mm Hg. These alterations were significantly less than those with CO2 pneumoperitoneum. Po2 decreased as well-from 266 +/- 30 to 212 +/- 21 mm Hg. During insufflation with both gases, peak ventilatory pressure and right atrial pressure increased significantly. Abdominal insufflation with CO2 or helium causes hypercarbia, acidemia, and increased ETCO2 in this juvenile animal model. These derangements are significantly less with helium. This gas may prove to be the more suitable insufflation agent for pediatric patients.

Operative treatment of gastroesophageal reflux in low birth weight infants.

Operative correction of symptomatic gastroesophageal reflux (GER) has been used frequently and successfully in both children and larger infants for many years. In contrast, surgical repair of GER has been applied relatively sparingly in very small infants because of perceived technical and postoperative difficulties. We retrospectively reviewed our experience with Nissen fundoplications performed for symptomatic GER in low birth weight (LBW) infants ( < or = 2500 grams the time of surgery). Twenty-one consecutive cases from 1988 to 1993 were evaluated. At the time of surgery, the average age was 9.1 weeks and the average weight was 2100 grams (range, 1220 to 2500 grams). All infants had failed a trial of medical management. Follow-up from 1 month to 5 years showed no intraoperative complications and resolution of symptoms in 91 per cent of our patients. Technical factors found to enhance the success of the operative repairs included appropriately sized dilators, division of the short gastric vessels, and a loose 360-degree wrap. With suitable technique, the surgical management of symptomatic GER can be performed safely in small infants.

Diagnosis and treatment of respiratory symptoms of initially unsuspected gastroesophageal reflux in infants.

Gastroesophageal reflux (GER) in infants is most commonly thought of as repeated excessive vomiting and failure to thrive, with most infants responding favorably to medical therapy. However, GER may also manifest exclusively with a variety of respiratory symptoms that, if not detected and treated early, may lead to life-threatening complications. During the period of 1987 to 1992, 39 neonates and infants underwent Nissen fundoplication for the treatment of respiratory symptoms attributed to GER. Symptoms included apnea and bradycardia (64%), pneumonia (31%), cyanosis (28%), cough (18%), and stridor (15%). Most patients were ascribed at least one incorrect diagnosis to explain respiratory symptoms. These include apnea of prematurity (38%), bronchopulmonary dysplasia (31%), asthma (8%), and subglottic stenosis (8%). All patients underwent a variety of investigations and medical treatments without noticeable clinical improvement. These included bronchoscopy, esophagoscopy, and polysomnograms. Treatment such as antibiotics, theophylline, bronchodilators, steroids, and oxygen were directed at presumed primary respiratory disease. On the other hand, H2 blockers, metoclopramide, positioning, and thickened feeds were prescribed to treat GER without objective evidence of disease. Ultimately, GER was demonstrated by upper gastrointestinal series in 64%, pH probe in 61%, and both studies in 38%. All patients underwent Nissen fundoplication after failed attempts at medical therapy. A total of 95% of patients had resolution or substantial improvement of respiratory symptoms postoperatively. Preoperative hospitalization averaged 37.0 days, and postoperative stay averaged only 14.2 days. We present a series of patients with GER, all of whom presented with respiratory symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombosis of abdominal aortic aneurysms.

The usual complication of abdominal aortic aneurysms is rupture. Although thrombosis of peripheral aneurysms is common, thrombosis of abdominal aortic aneurysms is rare. Sudden thrombosis of abdominal aortic aneurysms constitutes a surgical emergency, with a mortality of 50 percent. The patient often presents with cool and mottled skin, and with severe pain from the umbilicus to the lower extremities. Femoral pulses are rarely present, and neurologic deficits below the level of occlusion are common. We reviewed four recent patients with thrombosed abdominal aortic aneurysms. They presented with a range of symptoms that included impotence, abdominal pain, lower extremity pain, coolness, and weakness. Angiography in three of the patients revealed complete occlusion of the aorta. The fourth patient did not undergo angiography because of hemodynamic instability. Three of the four patients underwent thrombectomy, aneurysmectomy, and bypass grafting. The other patient underwent axillofemoral bypass grafting in lieu of aneurysmectomy because of severe coronary arteriosclerotic heart disease. All patients did well postoperatively. Our limited experience suggests that prompt diagnosis and surgical management of patients with thrombosed aortic aneurysms can lead to a successful outcome.

Effect of acute pretreatment of lead on picrotoxin-induced convulsions in rats.

The effect of acute exposure to lead acetate (LA)/lead nitrate (LN) on onset and severity of convulsions induced by a low dose of picrotoxin was examined in rats. Both LA and LN reduced the time of onset and exacerbated the severity of convulsions, with a resultant high lethality. On comparison, it was noted that in the LA-pretreated group, convulsion scores and incidence of tonus and mortality were much higher; the appearance of tonus was more delayed than in the LN-pretreated group. In lead-pretreated animals, the potentiation of picrotoxin-induced convulsions was accompanied by higher lead levels in blood (p < 0.001). However, the whole-brain lead levels were not significantly different in these animals compared to the controls. The difference in the degree of potentiation by the two forms of lead could possibly be attributed either to the role of a combination of anions and cations or to the variable cerebral uptake and regional distribution of lead or due partly to the extent of competitive interaction involving d-aminolaevulinic acid--whose level is known to be elevated consequent to lead-induced disruption of haem biosynthesis--at GABA receptors.