Effect of Various Toothpaste Tablets on Gloss and Surface Roughness of Resin-based Composite Materials.

OBJECTIVES: To evaluate the effect of various toothpaste tablets on gloss and surface roughness of resin-based composite. METHODS AND MATERIALS: Sixty-four resin-based composite specimens were divided into four groups of 16 specimens each. Gloss and roughness were measured before and after simulated brushing with three types of toothpaste tablets and one conventional toothpaste: CT: Chewtab Toothpaste Tablets; AT: Anticavity Toothpaste Tablets; HC: Charcoal Toothpaste Tablets; CP: Cavity Protection toothpaste. The Kruskal-- Wallis procedure was performed to compare the differences by groups. Post-hoc comparisons were conducted with Bonferroni corrections (α=0.05). RESULTS: There was a significant drop in gloss for all groups. CT and AT maintained the highest gloss with means of 81.6 GU and 74.1 GU, respectively. The lowest gloss of 24.5 GU was observed for HC. There was a significant increase in roughness for all groups except for CT. CT had the lowest roughness with a mean of 0.034 µm, while HC had the highest roughness with a mean of 0.074 µm. There was a significant correlation between post-brushing gloss and post-brushing roughness (p<0.001, r=-0.884). CONCLUSION: Chewtab Toothpaste Tablets had the least effect on gloss and roughness, while Charcoal Toothpaste Tablets had the most negative effect on the surface properties of resin-based composites.

First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743.

BACKGROUND: In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up. PATIENTS AND METHODS: Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or six cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including four-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs). RESULTS: With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months [hazard ratio (95% confidence interval), 0.73 (0.61-0.87)], and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the four-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for 1 year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation. CONCLUSIONS: With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.

The value of interventional radiology in clinical trial teams: experience from the BATTLE lung cancer trials.

AIM: To report on the multidisciplinary approach, focusing specifically on the role of the interventional radiologist (IR), used to support the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) and BATTLE-2 trials. MATERIALS AND METHODS: Patients who underwent percutaneous image-guided biopsy for the BATTLE and BATTLE-2 trials were reviewed. A radiology-based, three-point, lesion-scoring system was developed and used by two IRs. Lesions were given a score of 3 (most likely to yield sufficient material for biomarker analysis) if they met the following criteria: size >2 cm, solid mass, demonstrated imaging evidence of viability, and were technically easy to sample. Lesions not meeting all four criteria were scored 2 with the missing criteria noted as negative factors. Lesions considered to have risks that outweighed potential benefits receive a score of 1 and were not biopsied. Univariate and multivariate analyses were performed to evaluate the score's ability to predict successful yield for biomarker adequacy. RESULTS: A total of 555 biopsies were performed. The overall yield for analysis of the required biomarkers was 86.1% (478/555), and 84% (268/319) and 88.9% (210/236) for BATTLE and BATTLE-2, respectively (p=0.09). Lesions receiving a score of 3 were adequate for biomarker analysis in 89% of cases. Lesions receiving a score of 2 with more than two negative factors were adequate for molecular analysis in 69.2% (IR1, p=0.03) and 74% (IR2, p=0.04) of cases. The two IRs scored 78.4% of the lesions the same indicating moderate agreement (kappa=0.55; 95% confidence interval [CI]: 0.48, 0.61). CONCLUSIONS: IRs add value to clinical trial teams by optimising lesions selected for biopsy and biomarker analysis.

Behaviour change interventions to influence antimicrobial prescribing: a cross-sectional analysis of reports from UK state-of-the-art scientific conferences.

BACKGROUND: To improve the quality of antimicrobial stewardship (AMS) interventions the application of behavioural sciences supported by multidisciplinary collaboration has been recommended. We analysed major UK scientific research conferences to investigate AMS behaviour change intervention reporting. METHODS: Leading UK 2015 scientific conference abstracts for 30 clinical specialties were identified and interrogated. All AMS and/or antimicrobial resistance(AMR) abstracts were identified using validated search criteria. Abstracts were independently reviewed by four researchers with reported behavioural interventions classified using a behaviour change taxonomy. RESULTS: Conferences ran for 110 days with >57,000 delegates. 311/12,313(2.5%) AMS-AMR abstracts (oral and poster) were identified. 118/311(40%) were presented at the UK's infectious diseases/microbiology conference. 56/311(18%) AMS-AMR abstracts described behaviour change interventions. These were identified across 12/30(40%) conferences. The commonest abstract reporting behaviour change interventions were quality improvement projects [44/56 (79%)]. In total 71 unique behaviour change functions were identified. Policy categories; "guidelines" (16/71) and "service provision" (11/71) were the most frequently reported. Intervention functions; "education" (6/71), "persuasion" (7/71), and "enablement" (9/71) were also common. Only infection and primary care conferences reported studies that contained multiple behaviour change interventions. The remaining 10 specialties tended to report a narrow range of interventions focusing on "guidelines" and "enablement". CONCLUSION: Despite the benefits of behaviour change interventions on antimicrobial prescribing, very few AMS-AMR studies reported implementing them in 2015. AMS interventions must focus on promoting behaviour change towards antimicrobial prescribing. Greater focus must be placed on non-infection specialties to engage with the issue of behaviour change towards antimicrobial use.

Expression profiling stratifies mesothelioma tumors and signifies deregulation of spindle checkpoint pathway and microtubule network with therapeutic implications.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal neoplasm exhibiting resistance to most treatment regimens and requires effective therapeutic options. Though an effective strategy in many cancer, targeted therapy is relatively unexplored in MPM because the therapeutically important oncogenic pathways and networks in MPM are largely unknown. MATERIALS AND METHODS: We carried out gene expression microarray profiling of 53 surgically resected MPMs tumors along with paired normal tissue. We also carried out whole transcriptomic sequence (RNA-seq) analysis on eight tumor specimens. Taqman-based quantitative Reverse-transcription polymerase chain reaction (qRT-PCR), western analysis and immunohistochemistry (IHC) analysis of mitotic arrest deficient-like 1 (MAD2L1) was carried out on tissue specimens. Cell viability assays of MPM cell lines were carried out to assess sensitivity to specific small molecule inhibitors. RESULTS: Bioinformatics analysis of the microarray data followed by pathway analysis revealed that the mitotic spindle assembly checkpoint (MSAC) pathway was most significantly altered in MPM tumors with upregulation of 18 component genes, including MAD2L1 gene. We validated the microarray data for MAD2L1 expression using quantitative qRT-PCR and western blot analysis on tissue lysates. Additionally, we analyzed expression of the MAD2L1 protein by IHC using an independent tissue microarray set of 80 MPM tissue samples. Robust clustering of gene expression data revealed three novel subgroups of tumors, with unique expression profiles, and showed differential expression of MSAC pathway genes. Network analysis of the microarray data showed the cytoskeleton/spindle microtubules network was the second-most significantly affected network. We also demonstrate that a nontaxane small molecule inhibitor, epothilone B, targeting the microtubules have great efficacy in decreasing viability of 14 MPM cell lines. CONCLUSIONS: Overall, our findings show that MPM tumors have significant deregulation of the MSAC pathway and the microtubule network, it can be classified into three novel molecular subgroups of potential therapeutic importance and epothilone B is a promising therapeutic agent for MPM.

Eighth international mesothelioma interest group.

The eighth International Mesothelioma Interest Group (IMIG) meeting was held in Chicago, IL, United States, in 19-22 October 2006 to discuss mesothelioma - the cancer often linked to asbestos exposure. It is a very aggressive malignancy with a median survival of less than 1 year from diagnosis. Millions of people have been exposed worldwide to asbestos, especially during the second half of the twentieth century when asbestos use increased significantly. The tons of asbestos utilized in the past remain a health hazard for current and future generations because asbestos is difficult to be disposed off. This makes asbestos and mesothelioma research a public health issue in addition to a medical problem. Moreover, the very high costs of asbestos litigation have a significant impact on the whole economy. In the United States, up until 2001, defendant companies had paid 54 billion dollars in claims and estimated future liabilities ranged from 145 to 210 billion. Therefore, asbestos research is of great interest to a large audience that includes patients, millions of asbestos-exposed individuals, scientists, physicians, public health officials, politicians, unions of asbestos workers, lawyers and the public at large. During the past few years, there has been significant progress in understanding the process of mineral fiber carcinogenesis and mesothelioma pathogenesis. With improved understanding of the pathogenesis of mesothelioma, new diagnostic, preventive and therapeutic options are being developed. A total of 247 papers were presented at the IMIG: the abstracts of these presentations were published in Lung Cancer, Supplement 1, October 2006. Here, experts in different disciplines critically review some of the most exciting presentations of the IMIG meeting. The result is a comprehensive review of the research field of asbestos carcinogenesis and mesothelioma, and of the progress that has been made in recent years in both basic and clinical sciences.

Rapamycin enriches for CD4(+) CD25(+) CD27(+) Foxp3(+) regulatory T cells in ex vivo-expanded CD25-enriched products from healthy donors and patients with multiple sclerosis.

BACKGROUND: CD4(+) CD25(bright+) regulatory T cells (Treg) can be expanded to clinical doses using CD3/CD28 Ab-coated beads plus IL-2. However, this method requires high purity of the starting population to prevent overgrowth by non-regulatory T cells. Rapamycin, an agent that inhibits T-cell proliferation but selectively spares Treg, may be a means to expand Treg from less pure CD25-enriched cells. METHODS: CD25-enriched cells were prepared by a single-step immunomagnetic-selection using anti-CD25 microbeads. The cells were activated with a single addition of anti-CD3/CD28 beads and expanded in ex vivo 15-5% HS and autologous CD4(+) CD25(-) feeder cells,+/-rapamycin (0.01-20 ng/mL). IL-2 was added on day 3. Cells were rested for 2 days in ex vivo 15-5% HS and tested for phenotype, intracellular Foxp3 protein and suppressor activity. RESULTS: In the absence of rapamycin, CD25-enriched fractions expanded >17 000-fold by 21 days. Although suppressor activity was detected to day 14, it declined significantly by 21 days as non-regulatory cells expanded. The addition of rapamycin inhibited expansion of non-regulatory T cells at doses > or =1 ng/mL while increasing suppressor activity and the percentage of CD4(+) CD25(+) CD27(+) Foxp3(+) cells. Rapamycin did not enrich for Foxp3(+) cells in expanded cultures of CD4(+) CD25(-) cells. Treg were also readily expanded in cultures of CD25-enriched cells obtained from patients with multiple sclerosis in the presence of rapamycin. DISCUSSION: The addition of 1-20 ng/mL rapamycin to CD25-enriched cultures increased the purity of cells with the phenotype and function of Treg. This approach may alleviate the need for rigorous enrichment of Treg prior to activation and expansion for potential clinical use.

Cervical primitive neuroectodermal tumor.

BACKGROUND: Primitive neuroectodermal tumors (PNETs) are rare and potentially aggressive malignancies. CASE: A 24-year-old woman in her eighth week of pregnancy presented with a cervical mass. Tissue biopsy demonstrated poorly differentiated carcinosarcoma with neuroendocrine features. Immunohistochemical studies confirmed the diagnosis of PNET. Treatment included alternating courses of cyclophosphamide, adriamycin, vincristine (CAV) and ifosfamide, etoposide (IE). A radical hysterectomy with bilateral ovarian transposition and periaortic lymphadenectomy was performed with postoperative chemotherapy and radiotherapy. The patient remains disease free 2 years from therapy. CONCLUSION: This is a rare case of cervical PNET occurring in a pregnant patient. A review of the literature indicates that cervical PNET is distinguishable from uterine PNET. This tumor affects younger women and may have a different histogenesis. Pregnancy should not delay diagnosis of this potentially aggressive tumor.

Development of multianalyte sensor arrays composed of chemically derivatized polymeric microspheres localized in micromachined cavities.

The development of a chip-based sensor array composed of individually addressable polystyrene-poly(ethylene glycol) and agarose microspheres has been demonstrated. The microspheres are selectively arranged in micromachined cavities localized on silicon wafers. These cavities are created with an anisotropic etch and serve as miniaturized reaction vessels and analysis chambers. A single drop of fluid provides sufficient analysis media to complete approximately 100 assays in these microetch pits. The cavities possess pyramidal pit shapes with trans-wafer openings that allows for both fluid flow through the microreactors/analysis chambers and optical access to the chemically sensitive microspheres. Identification and quantitation of analytes occurs via colorimetric and fluorescence changes to receptor and indicator molecules that are covalently attached to termination sites on the polymeric microspheres. Spectral data are extracted from the array efficiently using a charge-coupled device allowing for the near-real-time digital analysis of complex fluids. The power and utility of this new microbead array detection methodology is demonstrated here for the analysis of complex fluids containing a variety of important classes of analytes including acids, bases, metal cations, metabolic cofactors, and antibody reagents.

Characterization of multicomponent monosaccharide solutions using an enzyme-based sensor array.

We report the development of a sensor for rapidly and simultaneously measuring multiple sugars in aqueous samples. In this strategy, enzyme-based assays are localized within an array of individually addressable sites on a micromachined silicon chip. Microspheres derivatized with monosaccharide-specific dehydrogenases are distributed to pyramidal cavities anisotropically etched in a wafer of silicon (100) and are exposed to sample solution that is forced through the cavities by a liquid chromatography pumping system. Production of fluorescent reporter molecules is monitored under stopped-flow conditions when localized dehydrogenase enzyme systems are exposed to their target sugars. We demonstrate the capability of this analysis strategy to quantify beta-D-glucose and beta-D-galactose at low micromolar to millimolar levels, with no detectable cross-talk between assay sites. Analysis is achieved either through fluorescence detection of an initial dehydrogenase product (NADH, NADPH) or by production of a secondary fluorescent product created by hydride transfer from the reduced nicotinamide cofactor to a fluorogenic reagent. The array format of this sensor provides capabilities for redundant analysis of sugars and for monitoring levels of other solution components known to affect the activity of enzymes. The use of this strategy to normalize raw fluorescence signals is demonstrated by the determination of glucose and pH on a single chip. Alternatively, uncertainties in the activity of an immobilized enzyme can be accounted for using standard additions, an approach used here in the determination of serum glucose.

Enzyme stabilization by covalent binding in nanoporous sol-gel glass for nonaqueous biocatalysis.

A unique nanoporous sol-gel glass possessing a highly ordered porous structure (with a pore size of 153 A in diameter) was examined for use as a support material for enzyme immobilization. A model enzyme, alpha-chymotrypsin, was efficiently bound onto the glass via a bifunctional ligand, trimethoxysilylpropanal, with an active enzyme loading of 0.54 wt%. The glass-bound chymotrypsin exhibited greatly enhanced stability both in aqueous solution and organic solvents. The half-life of the glass-bound alpha-chymotrypsin was >1000-fold higher than that of the native enzyme, as measured either in aqueous buffer or anhydrous methanol. The enhanced stability in methanol, which excludes the possibility of enzyme autolysis, particularly reflected that the covalent binding provides effective protection against enzyme inactivation caused by structural denaturation. In addition, the activity of the immobilized alpha-chymotrypsin was also much higher than that of the native enzyme in various organic solvents. From these results, it appears that the glass-enzyme complex developed in the present work can be used as a high-performance biocatalyst for various chemical processing applications, particularly in organic media. Published by John Wiley & Sons

The prevention of osteoporotic progression by means of steroid loaded TCPL drug delivery systems.

Numerous studies have suggested that there is a link between the age-related decreases in Estradiol and adrenal androgens, and the subsequent development of senile osteoporosis. The specific objectives of this investigation were: 1) to deliver Dehydroepiandrosterone (DHEA), Diosgenin (DG), and Estradiol (E) at sustained levels by Tri-Calcium Phosphate Lysine drug delivery systems (TCPL), and 2) to study the effects of the sustained delivery of DHEA, DG, and E on the bone turnover of adult female rats following withdrawal of the endogenous hormonal milieu by means of ovariectomization (OVX). In this study, 20 female Sprague-Dawley rats were randomly divided into five groups containing four rats per group. The rats in Group 1 served as intact controls. Animals in groups 2-5 were ovariectomized, and groups 3-5 were implanted immediately with TCPL drug delivery capsules containing DHEA, DG, and E, respectively. Group 2 served as the SHAM (OVX only) group. At the end of 33 days post implantation, the vital organs, reproductive organs, and femurs were collected and evaluated. Bone histomorphometric analyses as well as mechanical strength testing was performed. Data obtained from this study demonstrated that body weights were increased in all OVX animals, and that E replacement resulted in body weights that were not significantly different from intact controls. No differences were seen in the wet weights of any vital organs. However, a decrease in the weights of the cervix and oviducts were evident in all ovariectomized groups, with the exception of the E group. Thirty-three days following OVX, the OVX-only group exhibited an increased inner medullary area, decreased thickness of the cortical layer of bone, and decreased mechanical strength. The group treated with DHEA and the group treated with E were shown to maintain both the medullary area and the cortical thickness (as compared to the intact control group). The three point bending test of the femora showed that OVX-only induced a slight decline in mechanical strength, and that DHEA and DG, but not E, showed increases in mechanical strength. Results of this experiment suggest that DHEA and E may reduce bone remodeling as evidenced by the reduction in the medullary area, and that DHEA may possibly be used in postmenopausal patients to reduce osteoporotic progression.

The use of estrogen, DHEA, and diosgenin in a sustained delivery setting as a novel treatment approach for osteoporosis in the ovariectomized adult rat model.

It is well established that the pattern of bone loss from the cortex in osteoporotic bone begins from the endosteal surface of the cortex, where there is enlargement of the medullary canal at the expense of the inner cortex. Bone loss does not occur at the periosteal surface. The objective of the following study was to induce osteoporosis in female rats by ovariectomy, followed by treatment with sustained delivery of Diosgenin (DG), dehydroepiandrosterone (DHEA), or estrogen (E) after clinical signs of osteoporosis. Female Sprague Dawley rats were divided randomly into five groups containing four rats/group. Rats comprising group 1 were left intact and served as a control group. Animals in groups 2-5 were ovariectomized (OVX) and, after a 14 day delay to allow for induction of osteoporosis, were implanted with TCPL capsules containing DG, DHEA, and E, respectively. The experiment was ceased after 33 days of treatment, at which time the vital and reproductive organs for each group were collected, weighed, and analyzed histomorphometrically for differences. Further analysis of the progression of osteoporosis in the experimental animals was obtained by performing x-ray analysis of each group on a semi-weekly basis. By collecting and analyzing the femurs from each animal, we were also able to obtain important information about the histologic changes associated with osteoporosis (left femur), as well as data regarding the effects of osteoporosis on the mechanical strength of bone via three point bending analysis (right femur). The data generated by this study revealed important information as to the efficacy and safety of the alternative treatments DHEA, E, and DG for osteoporosis. First, histomorphometric analysis revealed that treatment with DHEA, E, and DG reduced the endosteal perimeter and cortical area to values very similar to controls (intact). Second, results of the bending stress and modulus in OVX and treated animals were not statistically different from the intact control animals, which suggests that the material properties of the bone were unaltered. Third, there is an increase in total body weight associated with OVX that is reduced to control levels after replacement therapy. Finally, OVX also resulted in reproductive tissue atrophy, which was reversed by all three of the treatment regimens in this study. These data suggest that bone loss after OVX can be significantly reduced by supplementation with sustained levels of DHEA, E, and DG without jeopardizing other body organs.

Morphometric analysis of cortical bone upon the exposure to sustained delivery of anabolic promoting agents using adult male rats as a model.

Several investigations have documented that the use of anabolic agents could promote osteogenesis and enhance bone ingrowth in traumatized bone. Previously, anabolic steroids have been shown to increase the mineralization of bone. However, their clinical use has been limited because of the unwanted virilizing activity. The previous studies used systemic administration of anabolic steroids, which subjects other tissues within the body to high concentrations of hormones. In addition, different anabolic/androgenic steroids have varying affinities to different cell types within tissues. The specific objectives of this study were (i) to histopathologically evaluate the structural changes associated with sustained delivery of testosterone (T), dihydrotestosterone (DHT), and androstendione (AED) using adult male rats as a model, and (ii) to morphometrically evaluate the cortical areas and length upon the exposure of the aforementioned hormones for 90 days. A total of 23 adult rats were randomly divided into five groups (group I = control, group II = sham, group III = AED, Group IV = T and group V = DHT treated). At the end of the treatments the animals were euthanized and the x-rays, blood, and bones were analyzed using standard laboratory protocols. Data obtained from this investigation revealed the following: (A) all treated femurs appeared healthy with no traumatic responses observed in comparison to control animals, (B) measurements of the inner perimeter of the bone on the endosteal side showed significant reduction in the androgen treated animals. This suggesting that the androgens caused increases in the cortical bone. The differences seen in the amount of reduction was in the following ease: T > DHT > AED. C) quantitative measurements of the cortical length showed slight increases in the cortical lengths in the androgen treated rats in comparison to the control.

The role of the route of administration of poly-chlorinated biphenyls (PCBs) on the reproductive and vital organs of adult female rats.

Studies have shown that high doses of Polychlorinated biphenyls (PCBs) given by conventional methods (orally or injections) have adverse effects on the reproductive and vital organs of adult female rats. However, there has not been documentation as to the effects of PCBs on adult female rats by means of a sustained delivery system. The specific objectives of this study were: (1) to investigate the effects of sustained delivery (TCPL ceramics) of PCB versus conventional mode of administration (injection) on the reproductive and vital organs of the adult female rat, (2) to evaluate the role that PCB that might have on the estrus events of adult female rats upon the exposure by sustained delivery (TCPL ceramics) and conventional mode (injection), and (3) to histopathologically evaluate the effect that PCB might have on the ovarian and accessory organs upon the sustained delivery for 21 days. A total of 10 adult female rats (BW 270-300 gm) were randomly divided into three groups. Group 1 (n = 3) served as the control, group 2 (n = 4) was injected intramuscularly every other day with Aroclor 1254 (0.1 cc), and each rat in-group 3 (n = 3) was implanted with TCPL capsules (5 mg of 2,3,3',4,5-Pentachlorobiphenyl). Aseptic surgical techniques were performed throughout the experiment. Blood (1 cc) was collected biweekly for biochemical analysis, and body weights were recorded as well. Pap smears were taken daily at approximately the same time for 25 days, and two slides were made for each pap taken (1 pap stain, 1 Diff Quik). At the end of 21 days post-implantation, all control and experimental animals were sacrificed following standard lab procedures (overdose of Halothane). The reproductive and vital organs were collected, weighed, fixed, embedded, sectioned, and stained (H&E) for histological evaluations. Data obtained from this investigation suggest the following: (1) TCPL devices were able to deliver PCB at sustained levels for 21 days, (2) regardless of the route of PCB administration no significant change was observed in total body weight compared to the controls, (3) conventional administration of PCB resulted in a remarkable changes in the fallopian tubes compared to control and sustained delivery implanted animals, (4) there were no obvious change was observed in the phases of estrus cycles upon the exposure of PCB, and (4) histopathological evaluation of spleen, kidneys, heart, adrenals, ovaries, uterus, and cervix tissues exposed to PCB did not reveal any significant changes compared to the intact group.

TCPL drug delivery system: the effects of synthetic DHEA and Diosgenin using an ovariectomized rat model.

Dehydroepiandrosterone (DHEA) has been shown in numerous studies to exhibit a host of benefits at the vital and reproductive organ levels. However, the use of naturally occurring DHEA is hindered by its inability to survive the first-pass metabolic process of the liver. One possible alternative means that deserves consideration is the administration of DHEA's precursor, namely, Diosgenin (DG). The specific objectives of this investigation were: 1) to deliver DHEA and DG at sustained levels by Tri-Calcium Phosphate Lysine (TCPL) drug delivery systems using ovariectomized (OVX) adult rats as a model, and 2) to evaluate the biochemical and histopathological changes associated with the sustained delivery of DHEA and DG. A total of 30 adult female rats were used in this investigation. The animals were further divided into 8 groups. Groups 1 and 2 animals served as intact control groups while each rat in groups 3-8 was ovariectomized (sham (33), n = 3 [group 3], sham (47), n = 4 [group 4]). Groups 5 and 6 were implanted with DHEA (group 5) and DG (group 6) loaded TCPL capsules immediately following the OVX procedure. Groups 7 and 8 were implanted with DHEA (group 7) and DG (group 8) loaded capsules 14 days following OVX. Surgical aseptic technique was employed according to standard laboratory protocols. Maliondialdehyde (MDA) and hormonal levels were measured from serum, collected semi-weekly, during the entire investigation (for 47 days) and X-rays were performed weekly. Pap smears were collected daily for 47 days to assess endometrial changes associated with DHEA and DG treatment. Following sacrifice (at day 33 for groups 1, 3, 5, and 6 and at day 47 for groups 2, 4, 7, and 8), routine H and E staining was conducted for histopathological evaluation of the reproductive and vital organs. Results of this investigation demonstrated: 1) OVX resulted in an increase in total body weight, and the use of DHEA and DG returned the body weight to near normal levels as compared to the intact control groups, 2) TCPL capsules delivered DHEA and DG at a sustained level during the 47 day study, 3) serum levels of MDA are as follows: DG > DHEA = OVX > control for the 33 day phase and OVX > DG > DHEA > control for the 47 day phase, 4) no significant changes were observed in total wet weights, as well as the morphology of the spleen, kidney, adrenal, heart, liver, and lung tissues, 5) OVX resulted in an atrophy and non-keratinization trend in the reproductive tissues, and sustained delivery of DHEA and DG showed no remarkable change in these tissues, 6) the use of sustained delivery of DHEA and DG resulted in higher weights of uteri compared to the OVX group. In conclusion, this study provided more information regarding the interrelationship between DHEA and DG, and the physiological responses encountered when they are administered continuously using the adult OVX rat as a model.

Morphological and biochemical modifications of human macrophages treated with various biomaterials.

Although tissue culture techniques are used extensively to explore the biocompatibility of various biomaterials used in orthopaedic, dental and pharmaceutical fields, the role of these materials towards human monocytes/macrophages has not been fully elucidated. The specific objectives of this investigation were: (1) to determine the biochemical markers resulting from exposure of the human monocytes/macrophages to titanium (TI), large size polyethylene (LSP), submicron polyethylene (SPE), hydroxyapatite (HA), large particle size tricalcium phosphate (LTCP), and small particle size tricalcium phosphate (STCP), and (2) to morphologically evaluate the viability of the cells treated with the aforementioned biomaterials. Approximately 15 volunteers donated blood for each phase (24, 48, and 72 hours) of the experiment. The monocytes were isolated by following established lab procedures (Histopaque 1077 and 1119). Aseptic techniques were followed throughout each phase. Each phase contained four experimental groups (TI, LSP, SPE, HA). Each group was comprised of six wells. The total protein, catalase, LDH, MDA, and cell count were measured using established lab protocols. Data obtained suggests that: (I) regardless of the biomaterial being used all experimental groups experienced remarkable phagocytosis in the first two phases (24, 48 hours), (II) during the 24 hour phase MDA activities were increased in TI, LTCP, and STCP treated wells when compared to the control and other experimental groups, (III) in the 48 hour phase the MDA level increased in LPE and STCP treated cells, (IV) there were significant differences in LDH levels in LPE, STCP, and SPE at 24 hours compared to the control and other experimental groups, (V) LDH activities were increased in LPE, STCP, SPE, and LTCP at 48 hours, and (VI) at 72 hours there were significant increases in catalase activity in HA, TI, SPE and LPE when compared to the control group and other experimental groups. Information obtained from this study provided new ideas about the interrelationship of various biomaterials, the effect of size and cell response to the various biomaterials.

Biochemical markers evaluation of RAW transformed cells during treatment with various biomaterials.

Upon introduction into the human body, biomaterials initially trigger a foreign-body inflammatory response. Furthermore, the wear debris associated with such materials as those used for orthopedic implants, artificial heart valves, and dental implants can cause the body to mount an inflammatory response. This involves the production of phagocytic macrophages that ingest the foreign material while simultaneously producing cytokines that serve as chemotactic agents for an amplified immune response. Currently titanium (Ti), polyethylene (PE), tricalcium phosphate (TCP) and hydroxyapatite (HA) are widely used as biomaterials in medical implants, and particle size is an important factor in the development of orthopedic, dental, and medical implants. The objective of this study was to investigate the effect of various biomaterials (Ti, mixed particle size polyethylene (MPE), ultra high molecular weight polyethylene (UHMWPE), mixed particle size TCP (MTCP), < 0.38 micron TCP (S-TCP), and hydroxyapatite (HA)) on the inflammatory reactions expressed by transformed RAW macrophages. RAW transformed monocytes were obtained from the American Cell Culture Line, (Rockville, MD). The cells were allowed to incubate in contact with the materials for intervals of 24, 48, and 72 hours. Biochemical tests and morphological evaluations were performed after each time point, including screening for cell number, cell protein levels, supernatant protein levels, lactate dehydrogenase (LDH), Maliondialdehyde (MDA), catalase by following standard lab protocols.