Search

Nasopharyngeal carcinoma (NPC) is a malignancy arising from the epithelium of the nasopharynx. Ethnic background, being exposed to the Epstein Barr virus, and increased alcohol use are risk factors for the development of NPC. The majority of patients are diagnosed when the cancer has spread beyond the local area. Radiation therapy, chemotherapy, and surgery are options for treating NPC and are dependent upon location and stage of the disease. Although NPC is a radiosensitive tumor, long-term survival for patients with advanced disease remains poor. The goal of this study was to determine if natural products (thymoqunione (TQ) and Epigallo-catechin-3-gallate (EgCg)) when given by continuous delivery methods rather than a single dose method would destroy cells over a shorter period of time than conventional delivery. The FaDu squamous cell carcinoma cell line was used to test repeated doses of natural (EgCg and TQ) drugs to determine if repeated doses would be as effective at destroying cancer cells as repeated doses of a known chemotherapeutic (5-FU) drug. Cells were treated repeatedly with IC50 concentrations of EgCg, TQ, and 5-FU at 24, 48, and 72 hours. Cells showed similar levels of cellular reduction at 72 hours. Increases in cellular membrane damage were observed in all treated groups with a significant difference seen in 5-FU treated cells compared to EgCg and TQ treated cells. Nitric oxide levels increased in a time dependent manner in EgCg and TQ treated groups. Overall, EgCg and TQ were proved they are as effective as 5-FU in cellular reduction and disrupting cellular function.

Nearly all persons with spinal cord injury (SCI) will develop osteoporosis following injury, and further, up to 50% of all persons with SCI will sustain a fracture during their lives. The unique mechanisms driving osteoporosis following SCI remain unknown. The cannabinoid system modulation of bone metabolism through cannabinoid 1/2 (CB1/2) has been of increasing interest for the preservation of bone mass and density in models of osteoporosis. Using a thoracic vertebral level 8 (T8) complete transection in a mouse model, we performed daily treatment with a selective CB2 receptor agonist, HU308, compared with SCI-vehicle-treated and naive control animals either immediately after injury for 40 days, or in a delayed paradigm, following 3 months after injury. The goal was to prevent or potentially reverse SCI-induced osteoporosis. In the acute phase, administration of the CB2 agonist was not able to preserve the rapid loss of cancellous bone. In the delayed-treatment paradigm, in cortical bone, HU308 increased cortical-area to total-area ratio and periosteal perimeter in the femur, and improved bone density in the distal femur and proximal tibia. Further, we report changes to the metaphyseal periosteum with increased presence of adipocyte and fat mass in the periosteum of SCI animals, which was not present in naive animals. The layer of fat increased markedly in HU308-treated animals compared with SCI-vehicle-treated animals. Overall, these data show that CB2 agonism targets a number of cell types that can influence overall bone quality.

Introduction: The federal government estimates that per mile traveled in 2018, the number of deaths on motorcycles was nearly 27 times the number in cars. In the United States there is no universal helmet law. In twenty-two states, motorcycle helmets are entirely optional, while in nineteen states and the District of Columbia universal motorcycle helmets laws requiring helmets for all riders regardless of age are implemented and nine states only require younger motorcycle riders to wear a helmet, with varying age limits. Objectives: The overall objectives of this study were to evaluate the following: (1) number of fatalities (with and without helmet use), (2) fatality rate per motorcycle registration, (3) fatality percentage with age, (4) percent fatality due to alcohol impairment, and (5) location of collision impact to the rider in two southern states (Mississippi and Alabama) where helmet laws are established compared with a southern state (Florida) that only requires riders less than 20 years of age to be helmeted. Methods: Data from 2015-2018 were obtained from the National Highway Transportation Safety Administration Reporting System (FARS) and supplemented with state related and CDC data. Results: In all three states, the most common collision was a front-end impact. Mississippi had the highest percentage of motorcycle fatalities even with >80% of riders helmeted when the fatal accident occurred, followed by Florida motorcyclist who are only 50% of the time helmeted. In all three southern states similar percentage of fatalities were seen in each age group with higher fatalities associated with age range of 30-39 years. Conclusions: Variables such as helmet type, distance from a level 1 trauma center, poor roads, weather conditions, and visibility of the rider may also be factors that contribute to a higher incidence of fatality and need to be further investigated to improve motorcycle safety.

BACKGROUND: High intraoperative PEEP with recruitment manoeuvres may improve perioperative outcomes. We re-examined this question by conducting a patient-level meta-analysis of three clinical trials in adult patients at increased risk for postoperative pulmonary complications who underwent non-cardiothoracic and non-neurological surgery. METHODS: The three trials enrolled patients at 128 hospitals in 24 countries from February 2011 to February 2018. All patients received volume-controlled ventilation with low tidal volume. Analyses were performed using one-stage, two-level, mixed modelling (site as a random effect; trial as a fixed effect). The primary outcome was a composite of postoperative pulmonary complications within the first week, analysed using mixed-effect logistic regression. Pre-specified subgroup analyses of nine patient characteristics and seven procedure and care-delivery characteristics were also performed. RESULTS: Complete datasets were available for 1913 participants ventilated with high PEEP and recruitment manoeuvres, compared with 1924 participants who received low PEEP. The primary outcome occurred in 562/1913 (29.4%) participants randomised to high PEEP, compared with 620/1924 (32.2%) participants randomised to low PEEP (unadjusted odds ratio [OR]=0.87; 95% confidence interval [95% CI], 0.75-1.01; P=0.06). Higher PEEP resulted in 87/1913 (4.5%) participants requiring interventions for desaturation, compared with 216/1924 (11.2%) participants randomised to low PEEP (OR=0.34; 95% CI, 0.26-0.45). Intraoperative hypotension was associated more frequently (784/1913 [41.0%]) with high PEEP, compared with low PEEP (579/1924 [30.1%]; OR=1.87; 95% CI, 1.60-2.17). CONCLUSIONS: High PEEP combined with recruitment manoeuvres during low tidal volume ventilation in patients undergoing major surgery did not reduce postoperative pulmonary complications. CLINICAL TRIAL REGISTRATION: NCT03937375 (Clinicaltrials.gov).

Lumbar spinal fusion is one of the more common spinal surgeries, and its use is on the rise. If the bone fails to fuse properly, then a pseudarthrosis or “false joint” develops and results in pain, instability, and disability. Since1974, three types of electrical stimulation technologies have been approved for clinical use to enhance spinal fusions. One such technology is inductive coupling, which includes combined magnetic fields (CMFs). The purpose of this study was to evaluate the effects of a CMF device known as the Donjoy (SpinaLogic®) on MG-63 (ATCC® CRL1427TM) human osteosarcoma cells at treatment depths ranging from 0.5” to 6.0”. The cells were grown to confluence on 4-well chamber slides that were kept in a nickel-alloy chamber within an incubator to shield the cells from unwanted environmental electromagnetic fields. During treatment, a specially designed apparatus held both the treatment device and the chamber slide. Briefly, the chamber slide was placed inside an acrylic tube at a specific distance from the transducer housing, and the device was turned on for 30 minutes. The chamber slides were then returned to the incubator to be evaluated at 7, 14, and 21 days post treatment for cell viability and bone nodule formation. Our results showed that compared to control cells, the cells located at 3” from the source had the greatest increase in bone nodule formation 7 days post treatment which is the depth at this consistent with manufacturer recommendations.

Study Objective: The aim of this study is to see if there are any clinical differences between using 35 F DLT for all patients versus using patient height regardless of gender to estimate appropriate DLT size. Design: Prospective randomized study. Setting: University Hospital. Patients: 50 patients age ≤18 years, undergoing lung or esophageal surgery requiring OLV. Interventions: Patients randomized to two groups (group-35F, group –DLT based on height). Measurements and Main Results: Data collected include demographics, ASA status, airway assessment, number of intubation attempts, Cormack-Lehane grade, number of times DLT repositioned, incidence of sore throat, oxygen saturation at induction and oxygen saturation at 5 minutes and 10 minutes after OLV. There was no statistically significant difference in demographics, ASA classification, Mallampati score, number of intubation attempts, Cormack-Lehane grade, number of times DLT was repositioned, and incidence of sore throat. In height based DLT group the odds were higher for the incidence of sore throat in 37-41 F group. Oxygen saturation at induction, 5 minutes and 10 minutes after OLV are not statistically significant between the two groups. Conclusion: Our findings suggest that the majority of patients receive unnecessarily large DLTs for thoracic surgery, which not only makes intubation inherently more difficult but also increases their risk of postoperative sore throat.

Background Opioid sparing anesthesia and enhanced recovery after surgery protocols are not innovative ideas. However, the utilization of pancreaticoduodenectomy is limited. With the rise in awareness of the opioid epidemic in the United States, we have created a multimodal approach to anesthesia and postoperative care to limit adverse effects of opioids and curb the use of opioids postoperatively. Methods We conducted a retrospective cohort study performed by chart review of an opioid-sparing anesthetic and enhanced recovery after surgery (ERAS) protocol initiated jointly by the anesthesiology departments and transplant surgery for pancreaticoduodenectomy from January 2017 to October 2019. Results Demographic data was found to be comparable between the control and protocol groups. Hospital length of stay, ICU length of stay, and opioid requirements significantly decreased in the protocol group. Hospital length of stay decreased from 8.92 to 5.72 days, ICU days decreased from 1.52 to 0.42 days, and narcotics for the first five hospital days were significantly decreased from 130.13 to 71.2 morphine milligram equivalents. Conclusion Proper postoperative pain management can improve patient satisfaction and decrease complication rates. Pancreaticoduodenectomy is a complicated procedure with relatively limited data regarding enhanced recovery after surgery protocols. Likewise, there is limited data regarding opioid-sparing anesthesia techniques. Our protocol produced promising hospital length of stay and reduced opioid administration during the first five hospital days without increasing 30-day readmission rates.

Background In the USA, spinal fusion surgery incurs the highest hospital cost. Despite the recent advances in the application of enhanced recovery after surgery (ERAS) protocols in these surgeries, the efficacy of these protocols in improving the perioperative outcomes remains unclear. We conducted a retrospective review as a quality improvement (QI) project to analyze the efficacy of the ERAS protocol with intraoperative modified thoracolumbar interfascial plane (mTLIP) block to determine whether these interventions reduce the length of stay (LOS) and opioid requirements during the postoperative period. Methods Retrospective reviews of adult patients (>18 yrs) who underwent elective lumbar spinal fusion or laminectomy at our institute were reviewed. Patients were administered oral gabapentin and acetaminophen preoperatively. Prior to incision, an mTLIP block was performed using liposomal bupivacaine. Intraoperatively, ketamine, ketorolac, and tranexamic acid were administered. Postoperative, pain control was treated with scheduled acetaminophen, ketorolac, and low-dose ketamine infusion. Hydromorphone and oxycodone were administered for breakthrough pain. Patients who underwent a similar procedure without ERAS protocol were chosen as controls to assess the efficacy of ERAS protocol. Data pertaining to patient demographics, operative and perioperative use of analgesics, LOS, 90-day readmissions, and morbidity were collected. Patients who underwent laminectomy and spinal fusion surgery were analyzed separately Results A total of 65 patients were identified; laminectomy (n- 24), spinal fusion surgery (n-41). In the laminectomy patients, treatment group (n-12) and the control group (n-12). Treatment group receiving the ERAS protocol with the regional anesthesia via the mTLIP (n= 12) opioid requirement was reduced by 51.42% [P = 0.03], and LOS was reduced by 2.04 days [P = 0.01] [0.75 days vs. 2.79 days]). In the spinal fusion patients, treatment group (n-15) and control group (n-26). Treatment group receiving the ERAS protocol with the use of regional anesthesia via the mTLIP group (n= 15), opioid requirement was reduced by 38.33% [P = 0.04]. No difference in LOS was observed at 5.4 days vs. 4.88 days (P = 0.28). Conclusion ERAS protocol in patients undergoing lumbar spinal surgery incorporated the use of regional anesthesia via the mTLIP block, we observed there is a statistically significant reduction in the LOS for lumbar laminectomy and a significant reduction in opioid administration for lumbar laminectomies and spinal fusion surgery.

Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. The present study was conducted to examine whether pioglitazone can reduce impairment of behavioral deficits mediated by inflammatory-induced brain white matter injury in neonatal rats. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 2 mg/kg) was administered to Sprague–Dawley rat pups on postnatal day 5 (P5), and i.p. administration of pioglitazone (20 mg/kg) or vehicle was performed 5 min after LPS injection. Sensorimotor behavioral tests were performed 24 h after LPS exposure, and changes in biochemistry of the brain was examined after these tests. The results show that systemic LPS exposure resulted in impaired sensorimotor behavioral performance, reduction of oligodendrocytes and mitochondrial activity, and increases in lipid peroxidation and brain inflammation, as indicated by the increment of interleukin-1β (IL-1β) levels and number of activated microglia in the neonatal rat brain. Pioglitazone treatment significantly improved LPS-induced neurobehavioral and physiological disturbances including the loss of body weight, hypothermia, righting reflex, wire-hanging maneuver, negative geotaxis, and hind-limb suspension in neonatal rats. The neuroprotective effect of pioglitazone against the loss of oligodendrocytes and mitochondrial activity was associated with attenuation of LPS-induced increment of thiobarbituric acid reactive substances (TBARS) content, IL-1β levels and number of activated microglia in neonatal rats. Our results show that pioglitazone prevents neurobehavioral disturbances induced by systemic LPS exposure in neonatal rats, and its neuroprotective effects are associated with its impact on microglial activation, IL-1β induction, lipid peroxidation, oligodendrocyte production and mitochondrial activity.

Study Design: Basic science. Objective: To compare the effects of a neuropeptide Y1 receptor antagonist (NPY-1RA) to estrogen on maintaining vertebral bone microarchitecture and disc height in a rat model of menopause. Methods: This study was an institutional animal care approved randomized control study with 104 ovariectomized rats and 32 intact control animals. Comparison of disc height, trabecular bone, body weights, circulating levels of NPY and estrogen, and distribution of Y1 receptors in the intervertebral disc in an established rodent osteoporotic model were made at baseline and after 2, 4, and 8 weeks after receiving either an implant containing estrogen or an antagonist to the neuropeptide Y1 receptor. Data was compared statistically using One-way analysis of variance. Results: Circulating levels of estrogen increased and NPY decreased following estrogen replacement, with values comparable to ovary-intact animals. NPY-1RA-treated animals had low estrogen and high NPY circulating levels and were similar to ovariectomized control rats. Both NPY-1RA and estrogen administration were able reduce, menopause associated weight gain. NPY-1RA appeared to restore bone formation and maintain disc height, while estrogen replacement prevented further bone loss. Conclusion: NPY-1RA in osteoporotic rats activates osteoblast production of bone and decreased marrow and body fat more effectively than estrogen replacement when delivered in similar concentrations. Annulus cells had NPY receptors, which may play a role in disc nutrition, extracellular matrix production, and pain signaling cascades.

The specific aim of this investigation was to investigate the effects of hydroxyapatite (HA) sintered at different temperatures on the proliferation, morphology, and cellular alterations of Embryonal Lung Fibroblasts (MRC-5) cells in culture. Microcrystals of HA were prepared by following standard laboratory protocols. The calcined HA was then placed on an automatic Tyler sieve stack to select for particles between 1-40 μm in size. The calcined material was sintered at 700, 1000, 1200 and 1300 °c for 24 hours. The sintered material (1.0 grams of HA) was added to a total of 20 mg of L-lysine as a binder. Finally, this combination was cold-pressed into cylindrical form using a 3/8 inch die set at a compression load of 5000 kg to form a disk of HA. Calculated density of the devices was directly proportional to temperature of sintering. MRC-5 fibroblasts were obtained from the American Type Culture Collection (ATCC). Proliferation Assessment, morphological evaluations were conducted following standard lab protocols. Cells were analyzed for Maliondialdehyde (MDA) levels by utilizing thiobarbituric acid reactive substance (TBARS) measurements. Results of this study revealed that there was an initial (at 24, and 48 hours) increase in proliferation rate observed in wells containing HA sintered at 700, 1000, and 1300°C. There were no significant differences in proliferating cells among control and capsules sintered at 1200°C (P

Spinal cord injury (SCI) results in perturbations to the immune system leading to increased infection susceptibility. In parallel, the consumption of high-fat diets (HFD) leads to a chronic inflammation in circulation and body tissues. We investigated the impact of 16 weeks of HFD on chronically-injured rats. SCI rats under both chow and HFD showed peripheral leukocyte changes that include reduced percentages of total, helper and cytotoxic T, and natural killer cells. Expression of immune-related genes in the spleen and thymus reflected the impact of both chronic injury and diet. Changes to the immune system following SCI are adversely impacted by HFD consumption.

The objective of this study was to quantitatively evaluate the possible morphological alterations that occur in the columnar epithelial cells of the prostate peripheral zone during early development of benign prostatic hyperplasia (BPH). In this study, BPH was induced by the continuous and sustained delivery of Danazol (androgen analog) through tricalcium phosphate-lysine (TCPL) drug delivery devices (OD: 0.8 mm, ID: 0.4 mm and density: 1.98 ± 0.53 gm/cm3). A total of 24 adult male rats (BW: 280-320 gm) were randomly divided into three equal groups. Group 1 served as an intact control and Groups 2-3 were implanted with TCPL devices designed to deliver continuous physiologic (3-5 ng/ml) doses of Danazol (DZ) following standard laboratory surgical methods. Upon completion of the study (12 weeks), the resected prostate were subjected to histopathological evaluation. Specifically, the columnar epithelial cells were targeted for morphometric analysis. The means number of cells per high power field, cell length, cell area; nuclear area and nuclear to cytoplasmic ratio (N/C) were measured using digital image analysis software technique. The results of this study revealed that: (i) the number of cells per high power field were unchanged with DZ exposure (log 1.22 ± 0.32) compared to controls (log 1.22 ± 0.26); (ii) the cell length was significantly (P < 0.05) decreased with upon DZ exposure (0.9 ± 0.03 µm) compared to controls (1.32 ± 0.51 µm), (iii) the cellular area was decreased with DZ (1.02 ± 0.056 µm 2) compared to controls (1.59 ± 0.102 µm 2 , and (iv) the N/C ratio was increased (0.279 ± 0.032 um) compared to controls (0.188 ± 0.021 µm). The results of this study suggest that sustained delivery of DZ by TCPL modality resulted in a remarkable alteration during early development of BPH. These finding may alert a pre-dysplastic outcomes from sustained delivery of DZ.

The compositional balance and distribution of trace metals/elements in various body tissues are essential key players in tissue and cellular homeostasis. Low Zn levels as well as overexpression of metalothioneins were implicated in the development and progression of various cancers including the prostate. Nonetheless, wider elemental profiles that relate cancer and normal phenotypes with regards to metal homeostasis were not well elucidated in the literature. Moreover, laboratory animals are currently used as accepted models for studying cancer but the level of their representation of actual cancer tissues was not clear. This study is attempting to assess the relevance of animal models currently in use, as surrogates for cancer and establish their relationship to actual normal and cancer tissues from humans. The major focus of this study was to investigate the differential relationship of metal concentrations and profiles in cancer and normal tissues from cadavers of humans and their comparison to established animal models representing organ cancers. The working hypothesis was that elemental/metal concentrations and profiles seen in post mortem will show significant differences between normal and cancer-derived tissues as well as between various tissue types in humans, rats, and dogs. This study also establishes critical elemental/metal profiles that may be relevant in providing correlations with the development of three major cancers. Normal human and tumor tissues of cadaverous lung, breast, and liver used in this study were obtained from US Biomax Company and relevant animal models (Sprague-dawley and Brown Norwegian rats as well as dogs; were obtained from Jackson Laboratories and the Mississippi State Veterinary Laboratory in Pearl, MS), to analyze for elements and test the hypothesis. Tissue samples were prepared using standardized digestion procedures necessary for use with the Inductively Coupled Plasma-Atomic Emission mass Spectrometry (ICP-MS) to determine the concentrations and profiles of 21 elements including Ag, Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Na, Ni, Pb, Sb, Se, Sr, Tl, V, and Zn. Our data supports the notion that metal/elemental homeostasis is essential for normal tissue function and that elemental variations in content, distributions, and ranking are tissue specific as well as carcinoma and species-specific. Analysis of data showed significant variations in elemental content and distribution profiles/ranking between animal models and actual human tissues consistent with the hypothesis. It is concluded that elemental homeostasis is essential for normal tissue function and that shifts in their distribution and content are essential in determining the use of animal models as surrogates for studying cancer. These results are promising and warrant further studies to confirm the relevance of animal models in relation to their use as pre-clinical tools for examining targeted cancer therapeutics.

The specific objective of this investigation is to study the effect of tetracalcium phosphate (TeCP) delivery system fabricated from three different particle sizes (6 HL-60 cells. At the end of 24, 48, and 72 hours, the supernatants (cell suspension) from the wells were collected for cell count (a hemacytometer method) and lactate dehydrogenase (LDH) assays. The cells were evaluated for structural cellular damage by using conventional histopathological protocols (H&E stain). Results obtained from this investigation suggest the followings: (i) particle sizes are key elements in developing TeCP delivery system, (ii) the use of

Grand Bay National Estuarine Research Reserve (GBNERR) is an important ecosystem in the Mississippi Gulf Coast. The GBNERR may be a potential source for contamination with anthropogenic bacterial pathogens that may play a significant role in the causation of waterborne human diseases. The objective of this study was to evaluate the interaction of physicochemical and microbiological water quality parameters at the GBNERR to determine quantitative levels and establish the potential for remediation of post-contamination of water and seafood by human fecal pollution from anthropogenic sources at the reserve. Water samples were collected aseptically from Bayous Heron, Cumbest, Point Aux Chenes Bay and Bangs Lake (Pine-O-Pine). Physicochemical parameters were determined using standard protocols. Eight bacterial species including Campylobacter were concentrated from water samples by membrane filtration. Water samples were tested for the presence of traditional indicator microorganisms including: heterotrophic (HPC), total coliforms (TC), fecal coliforms (FC), and enterococcus (ENT) in CFU/ml concentrations. Mean values of temperature, specific conductivity, dissolved oxygen, and pH were within acceptable levels in comparison to MDEQ, USEPA, and the USGS standards during the time of investigation. However, the values of turbidity in Grand Bay water exceeded USEPA recommended levels in several occasions during the investigation. Data from this study indicates significant variability (p < 0.0001) in mean bacteria concentrations between sites. The data also indicates significant impact of acetic acid treatment in the remediation of post contamination and survival of pathogens from the GBNERR Bayous Heron, Cumbest, and Pine-O-Pine when compared with control findings. The interaction of physicochemical and microbiological parameters of water through external chemical manipulation by acetic acid may provide utility in the remediation of post-contamination with anthropogenic pathogens such as E. coli, Enterococci, Campylobacter, Vibrio, Giardia, and Cryptosporidium. Presence of high numbers of indicator bacteria suggests public health concerns for oyster and shellfish consumers as well as other water contact activities. Hence, control strategies should be developed and implemented to prevent or remediate any future contamination of the GBNERR waters citing the economic impact of such contamination on shellfish fishing activities on the reserve.

Perinatal inflammation-induced reduction in pain threshold may alter pain sensitivity to hyperalgesia or allodynia which may persist into adulthood. In this study, we investigated the anti-inflammatory protective effect of interleukin-1 receptor antagonist (IL-1ra), an anti-inflammatory cytokine, on systemic lipopolysaccharide (LPS)-induced spinal cord inflammation and oxidative stress, thermal hyperalgesia, and mechanical allodynia in neonatal rats. Intraperitoneal (i.p.) injection of LPS (2 mg/kg) or sterile saline was performed in postnatal day 5 (P5) rat pups, and IL-1ra (100 mg/kg) or saline was administered (i.p.) 5 min after LPS injection. Pain reflex behavior, spinal cord inflammation and oxidative stress were examined 24 h after LPS administration. Systemic LPS exposure led to a reduction of tactile threshold in the von Frey filament tests (mechanical allodynia) and pain response latency in the tail-flick test (thermal hyperalgesia) of P6 neonatal rats. Spinal cord inflammation was indicated by the increased numbers of activated glial cells including microglia (Iba1+) and astrocytes (GFAP+), and elevated levels of pro-inflammatory cytokine interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) 24 h after LPS treatment. LPS treatment induced spinal oxidative stress as evidenced by the increase in thiobarbituric acid reactive substances (TBARS) content in the spinal cord. LPS exposure also led to a significant increase in oligodendrocyte lineage population (Olig2+) and mature oligodendrocyte cells (APC+) in the neonatal rat spinal cord. IL-1ra treatment significantly reduced LPS-induced effects including hyperalgesia, allodynia, the increased number of activated microglia, astrocytes and oligodendrocytes, and elevated levels of IL-1β, COX-2, PGE2, and lipid peroxidation (TBARS) in the neonatal rat spinal cord. These data suggest that IL-1ra provides a protective effect against the development of pain hypersensitivity, spinal cord inflammation and oxidative stress in the neonatal rats following LPS exposure, which may be associated with the blockade of LPS-induced pro-inflammatory cytokine IL-1β.

The role of retinoic acid (All Trans Retinoic Acid; ATRA) in the development of hypervitaminosis A pathophysiology is not well understood or established in the literature. As well, the role of Citral (inhibitor of retinoid function; a non-toxic chemical that exists in two forms (diethyl; C1 or cis-trans dimethyl; C2).) in the reversal of pathophysiological implications is also not ascertained under an in vivo setting. Therefore, it is hypothesized that ovalbumin exposure will sensitize the body to supra-physiologic levels of retinoic acid leading to a negative pathophysiological impact and that Citrals 1 and 2 will reverse or ameliorate the related damage to the body’s pathophysiology. Even though ovalbumin and retinoic have been previously applied through intra-tracheal route in cancer prevention and immunological research, the objective of this study was to evaluate their interaction as a remedy for hypervitaminosis A. This IACUC approved in vivo study used Fischer 344 rats (n = 80 ;229 to 273g), which were randomly assigned to controls as well as ovalbumin and mold-sensitized treatment groups (0.80 mg/kg and 1X109 mold spores combined from 4 strains/100 μl intra-tracheal; all others were dosed by intra-peritoneal injection at days 1 and 7 with 80 mg/kg each of ATRA as well as 20 and 50 mg/kg each of Citrals 1 or 2 individually or in combination to represent all four chemicals and mold spores treatments.. Positive and negative controls for each treatment were also included in the study. Animals were housed in rat cages at the JSU Research Animal Core Facilities and were placed on a 12:12 light dark cycle. A standard rodent diet and water access were provided ad-libidum. Rat weights were recorded on day 1 and 21, all animals were sacrificed on day 21 and blood was collected and processed for hematological parameters. Results showed that even though C1 and C2 were not toxic individually, their combination at high dosing was lethal. Exposure of ovalbumin-sensitized rats to ATRA showed various levels of weight losses and negative hematological implications that were ameliorated by exposure to Citrals at various combinations with retinoic acid. Taken together, the study showed that there are variable pathophysiological responses from the interaction of ovalbumin, mold spores and retinoic acid and that Citrals were found to be individually effective in reversing health-related pathophysiologies. These findings warrants further investigations as to the actual role of these interactions in relation to acute pathophysiologic health implications and the possibility of reversing hypervitaminosis A-mediated health-related impacts.

The paradoxical role of retinoic acid (All Trans Retinoic Acid; ATRA) in the development of allergic and/or inflammatory complications in contrast to a therapeutic modality for lung pathology is not well understood or established in the literature. As well, the role of Citral (inhibitor of retinoid function; a non-toxic chemical that exists in two forms (diethyl; C1 or cis-trans dimethyl; C2), in the reversal of retinoic acid, ovalbumin and allergic mold spore pathophysiology is also not well ascertained under an in vivo setting. Therefore, it is hypothesized that exposure of F344 lung tissues to supra-physiologic levels of retinoic acid, ovalbumin and mold spores individually or in combination with each other will lead to inflammatory tissue pathology and that Citral 1 and 2 will reverse or ameliorate the related pathological damage to lung tissues. Even though ovalbumin and retinoic acid have been previously applied through intra-tracheal route in cancer prevention and immunological research, the objective of this study was to evaluate the histopathological implications of such exposure in vivo. This IACUC approved in vivo study used Fischer 344 rats (n = 80 ; 229 to 273g), which were randomly assigned to controls as well as ovalbumin and mold-sensitized treatment groups (0.80 mg/kg and 1×109 mold spores combined from 4 strains/100 μl intra-tracheal; all others were dosed by intra-peritoneal injection at days 1 and 7 with 80 mg/kg each of ATRA as well as 20 and 50 mg/kg each of Citrals 1 or 2 individually or in combination to represent all four chemicals and mold spores treatments. Positive and negative controls for each treatment were also included in the study. Animals were housed in rat cages at the JSU Research Animal Core Facilities and were placed on a 12:12 light–dark cycle. A standard rodent diet and water access were provided ad libidum. All animals were sacrificed on day 21 and lung tissues were processed for histopathology. Slides were prepared and were digitized for comparison of tissues pathology. Results showed that exposure of the F344 rats to ovalbumin and ATRA showed various levels of lung tissue damage that was ameliorated by Citral 2 in combination. Mold and ATRA exposure caused various levels of lung tissue damage that was reversed by C1 in combination with each other. Taken together, the study showed that there are variable pathologic inflammatory responses from the interaction of ovalbumin, Citrals, mold spores and retinoic acid, and that the addition of Citrals have reversed lung tissue pathologies. These findings warrants further investigation as to the actual role of these interactions in relation to acute/chronic lung disease and the possibility of reversing retinoid-mediated pathologies in the Fisher rat model.

The goals of this study are to evaluate the ability of the multicomponent collagen-elastin-like polypeptide (ELP)-Bioglass scaffolds to support osteogenesis of rat mesenchymal stem cells (rMSCs), demonstrate in vivo biocompatibility by subcutaneous implantation in Sprague-Dawley rats, monitor degradation noninvasively, and finally assess the scaffold's ability in healing critical-sized cranial bone defects. The collagen-ELP-Bioglass scaffold supports the in vitro osteogenic differentiation of rMSCs over a 3 week culture period. The cellular (rMSC-containing) or acellular scaffolds implanted in the subcutaneous pockets of rats do not cause any local or systemic toxic effects or tumors. The real-time monitoring of the fluorescently labeled scaffolds by IVIS reveals that the scaffolds remain at the site of implantation for up to three weeks, during which they degrade gradually. Micro-CT analysis shows that the bilateral cranial critical-sized defects created in rats lead to greater bone regeneration when filled with cellular scaffolds. Bone mineral density and bone microarchitectural parameters are comparable among different scaffold groups, but the histological analysis reveals increased formation of high-quality mature bone in the cellular group, while the acellular group has immature bone and organized connective tissue. These results suggest that the rMSC-seeded collagen-ELP-Bioglass composite scaffolds can aid in better bone healing process.

In this study, attitudes and perceptions of U.S. dental students and faculty members were evaluated regarding four aspects of dental education: technology integration, instructional strategies, student diversity, and school duration. A survey instrument with eight statements using a five-point Likert scale and a free-text comment section was developed and distributed through Survey Monkey. A total of 426 students and 187 faculty members from ten U.S. dental schools participated, a response rate of 17 percent of those surveyed. Faculty and student responses were compared using the Mann-Whitney U test. The results of this analytic procedure revealed that the groups differed in their average responses for seven of the eight statements. Analysis of the faculty and student comments revealed similar themes between the two groups. Both dental students and dental faculty members stated that technology integration should be viewed as only a supplement to conventional instruction and showed mixed opinions about electronic textbooks. Further, both groups had positive views of the roles of problem-based learning, community service, and the integration of research practice into dental education. Both groups also valued diversity in the student body and supported the current four-year duration of dental school.

This study investigates conventional delivery of thymoquinone (TQ) and epigallocatechin-3-gallate (EGCG) when applied to Caov-3 and SK-OV-3 ovarian like cell lines. Culturing the cells and assessment of functional activities were conducted following standard lab protocols. The results revealed: (1) an increase in the SK-OV-3 cell protein levels following treatment with TQ+EGCG which was statistically different (p

It is well documented that glucocorticoids are potent anti-inflammatory and immunosuppressive agents that are known to affect cell mediated inflammation by the inhibition of cellular proliferation and cytokine production. The literature is lacking knowledge in elucidating the mode of action of such agents on the transformed like cells in culture. Therefore, RAW (macrophage like) cells was selected as a model to determine the effects of cortisol administration or cortisol in the presence of LPS on the cells metabolic functions. Cells were treated with physiological concentrations of cortisol or cortisol + LPS for periods of 24, 48 and 72 hours. After each phase, cell numbers, cellular damage and cellular morphology were determined. The results indicated cortisol and cortisol + LPS treated cells inhibited cellular proliferation as well as increased cellular MDA levels as early as 24 hours. Overall, the results indicate that cortisol has a remarkable effect on RAW cellular proliferation similar to the reduction seen in our previous findings using HEP-2 cells. In addition to reduction in cellular number the cell's ability to adjust to a bacterial challenge may be directly altered. These results provided important information for patients who are immunosuppressed or chronically exposed to stressful conditions.

The route of administration of ovarian hormones and other biologicals represent a key factor in the treatment, prevention or eradication of different diseases in humans. Many studies have documented that the use of sustained delivery of biologicals is more effective compared to conventional route of administration. To date, the literature is lacking studies that conclusively demonstrate the change on body weights and vital organ morphology associated with sustained delivery of Neuropeptide Y antagonist and estrogen compared to intact and ovariectomized adults as a model. Therefore, the purpose of this study represents a histopathologic evaluation of the sustained delivery of ovarian hormones and neuropeptide y antagonist on the body weight and vital organs of ovariectomized rats. A total of 25 Sprague Dawley rats were obtained and divided into five groups, intact control with ovaries, sham, OVX + estrogen, and NPY antagonist. Animals in three of the five groups were surgically implanted with a TCP drug delivery device loaded with 1.6 mg of estrogen and 1.6 mg of NPY antagonist, and the sham animals were implanted with empty capsules. The capsules were surgically inserted into the muscle adjacent to the six lumbar vertebra. The animals were euthanized at two weeks, post-implantation phases. An analysis of the body weights were compared, and the OVX + estrogen and the OVX + NPY antagonist were similar to the intact control animals. Histopathologic evaluation of the major body organs revealed no histopathological change in the adrenals, spleen, liver, lungs or heart muscles of the intact, OVX, sham and NPY antagonist low and high dose treated animals. The only significant difference was observed in the kidney, where the glomeruli appeared much larger in the estrogen treated animals. Overall conclusion obtained from this study demonstrated that TCPL delivery can be used effectively to administer NPY at sustained level with remarkable reduction in side effects that associated with conventional means.

The purpose of this investigation was to determine fibroblast behavior after implantation of ultra-high molecular weight polyethylene (UHMW-PE) rinsed with saline (control) or coated with poly-L-lysine (PLL), arginine-glycine-aspartic acid (RGD), or arginine-glycine-glutamic acid (RGE) into 16 adult male rats subcutaneously. At 90 days post-implantation, fibroblast counts were highest in the saline rinsed group (34±2 cells/HPF) and significantly reduced in RGD (19±10), RGE (2±3), and PLL (0) treated groups. These findings indicate fibroblast migration in surrounding fibrous tissue can be strongly influenced using various amino acid combination coatings in subcutaneous applications.

Introduction To examine factors potentially contributing to premature cardiovascular disease mortality in African Americans (40% versus 20% all other populations), plasma homocysteine, serum vitamin B12 and folate levels were examined for African American participants in the Jackson Heart Study. Methods Of 5192 African American Jackson Heart Study participants (21–94 years), 5064 (mean age, 55 ± 13 years; 63% female) had homocysteine levels measured via fasting blood samples, with further assessments of participants’ vitamin B12 (n = 1790) and folate (n = 1788) levels. Regression analyses were used to examine age, gender, vitamin B12 and folate with homocysteine levels. Results Homocysteine levels, a purported surrogate risk factor for cardiovascular disease, increased with age, were inversely proportional to folate and vitamin B12 levels ( P Conclusions The results show that, as with other populations, age, gender, vitamin B12 and folate may predict homocysteine levels for African Americans. Diet may be an important predictive factor as well, given the relationships that were observed between plasma homocysteine and serum B vitamin levels.

Study design: Randomized controlled animal trial. Objectives: To analyze the early and late phase effects of platelet-rich plasma (PRP) injection into and around the damaged intervertebral disc using an animal model, and to evaluate the needle puncture technique in creating a degenerative disc model. Methods: The L4-L5 intervertebral disc of 18 adult Sprague-Dawley rats was injured with a 21-gauge needle. Animals received an immediate injection of PRP, or a delayed injection of PRP 2 weeks postinjury, or no further intervention (sham) (n = 6/group). Six uninjured controls were used. Magnetic resonance imaging (MRI) was performed for a control at time 0 and each group at 4 weeks postinjury, this allowed resolution of inflammation and an accurate assessment of healing. Specimens were collected from immediate PRP group at 2 and 4 weeks postinjury, and the delayed PRP group at 4 and 6 weeks postinjury. The sham and control specimens were collected at 2, 4, and 6 weeks postinjury. Each disc was sectioned and analyzed subjectively for overall structure, cellularity, and water content (utilizing MRI). Disc height was measured using descriptive statistics and one-way analysis of variance (ANOVA) with Tukey post hoc analysis. It was presumed both groups injected with PRP would have better outcomes than the sham group. Results: The sham group had clear degenerative changes with loss of organizational structure, empty space, fibrous tissue, and inflammatory cells, indicating needle puncture leads to degeneration. The PRP treated groups had fibers that were damaged with empty spaces and inflammatory cells. However, there was maintenance of the ring structure and the nucleus appeared to have a healthy central portion. Overall, both PRP - treated groups retained more normal morphologic features, contained fewer inflammatory cells, and had higher fluid content on MRI; however the effect was more pronounced in the immediate injection group. The disc height was significantly different in the sham and immediate injection group at the 4-week interval. Conclusions: This percutaneous needle puncture technique is an effective method for creating a degenerative disc model without posterior destabilization of the spine. The administration of PRP has a protective effect on damaged discs in the acute and delayed injection settings representing clinical treatment with PRP in the early versus late stages of the degenerative process. It appears that earlier intervention in the disease process would be more beneficial than PRP treatment of already severely degenerated discs.

Study design: Randomized controlled trial. Objective: To compare fusion rates, time to fusion, complication rates and subsidence between 1) a static, 2) a dynamic angulation, and 3) a dynamic translation plate in anterior cervical discectomy and fusion for symptomatic degenerative cervical disease. Methods: Thirty-six patients with two level, symptomatic cervical degenerative changes requiring surgery were randomized in a blinded fashion to receive a statically locked plate, Cervical Spine Locking Plate (CSLP) (Synthes, Paoli, PN, USA), an Atlantis Vision® Anterior Cervical Plate System (Medtronic, Memphis, TN, USA) which allows angular dynamization, or a Premier® Anterior Cervical Plate System (Medtronic) which allows translational dynamization. Structured data collection and measurement protocols were used. Intervertebral composite allograft cages were used in all groups. Identical external immobilization and antiinflammatory medication protocols were followed. X-rays were obtained at preset time points postoperatively. Assessment of the primary outcomes was blinded. Rate of and time to fusion, graft/instrumentation complications, subsidence, and reoperation for adjacent level disease were measured. Paired t-test and three-way Analysis of Variance test (ANOVA) were used to assess statistical differences between groups. Results: The three groups were similar demographically. Fusion rates in the CSLP, Atlantis and Premier plate groups were 100%, 91%, and 92% respectively. Mean time to fusion was 6.1, 8.3 and 6.3 months respectively but differences were not statistically significant. Mean subsidence in the groups was 1.9, 1.6, and 2.6 mm respectively. Subsidence was found even for the static (CSLP) plate, but no statistically significant differences were found. Conclusions: We found no clinical advantage of dynamic plates over static plates with regards to fusion rates, time to fusion, subsidence, complications, or adjacent-level surgery. Static plating allows for subsidence at similar levels to dynamic plating. Methods evaluation and class of evidence (CoE) Methodological principle: Study design: RCT • Cohort Case control Case series Concealed allocation (RCT) Intent to treat (RCT) • Blinded/independent evaluation of primary outcome • Complete follow-up of ≥85%* • Adequate sample size Control for confounding† • Evidence class: II *Reliable data are data such as mortality or reoperation. †Authors must provide a description of robust baseline characteristics, and control for those that are unequally distributed between treatment groups. View it in a separate window The definiton of the different classes of evidence is available on page 83.

Background:Management of fungal osteomyelitis is prolonged and frequently unsuccessful. Antifungal-impregnated cement is sometimes used as adjunctive therapy.Objective:To examine the release of antifungals from biodegradable and nonbiodegradable cement carriers.Methods:In vitro methods were used to assess antifungal drug release and antifungal activity of impregnated cements commonly used as adjunctive treatment of osteomyelitis. Cements included thermoplastic, nonbioactive polymers (polymethylmethacrylate [PMMA]) or bioactive agents (hydroxyapatite [HAP], β-tricalcium phosphate [β-TCP]) and were formed into spheres (beads).Results:Amphotericin B provided consistent supernatant concentrations (release), between 1.75 and 2.0 ug/mL, over 110 days from all bone cements. Flucytosine and fluconazole were observed for 33–42 days before becoming undetectable from a nonbioactive sphere and 18–22 days from a bioactive sphere. Serum concentrations for micafungin, terbinafine, and anidulafungin impregnated into PMMA rapidly became undetectable, regardless of the matrix used. Investigational β-TCP spheres prolonged release for fluconazole and micafungin, but had no effect on amphotericin B. Serum calcium concentrations decreased 60–80% in all HAP-impregnated drug sphere supernatants. Only amphotericin B–impregnated PMMA impacted supernatant calcium, decreasing concentrations by 50–60%. The antifungal-impregnated beads did not appear to be toxic to osteoblasts during 72 hours of exposure in tissue culture medium.Conclusions:Elution characteristics of most antifungals from bone cement spheres are probably not optima) for treatment of deep-seated fungal infections if a similar phenomenon of antifungal release manifests in vivo. Ceramic nonabsorbable impregnated devices must be removed after their lifespan expires and may necessitate another surgical procedure that can increase surgical risk and cost. Bioactive osteoconductive materials may provide a surgical alternative to nonabsorbable matrices. However, there have been no controlled trials demonstrating improved therapeutic outcomes with local therapy and assessing whether biodegradable materials act as a new focus for infection.

The impact of retinoic acid (All Trans Retinoic Acid; ATRA) and Mold spores (MLD) in the development of lung pathology and in vivo tissue remodeling have not been well established in the literature. In addition, the role of citral (inhibitor of retinoid function) in the improvement of lung pathology has not been ascertained in animal studies. Therefore, it is hypothesized that ATRA and Mold (MLD) exposure will sensitize lung tissues leading to lung tissue pathology and that Citrals (C1 and C2) will reverse, ameliorate or improve the associated pathological damage to lung tissues. The study used an IACUC approved between-subject in vivo randomized split plot factorial design (F344 rat model; N=40). Animals were exposed to eight different treatments including vehicle, MLD, ATRA, Citrals (C1 and C2) and their MLD combinations (MLD+ ATRA, MLD+ C1, and MLD+ C2) by intra-peritoneal route. Rat weight and blood data were collected on Days 1 and 21, all animals were sacrificed on day 21, and lung tissues were processed for histopathology. Results from weight and blood data (ANOVA and Duncan) as well as from histopathological analyses supported the findings that exposure of F344 rats to MLD combinations with ATRA and Citrals showed various levels of lung tissue damage that were impacted by either C1 or C2. This promising study showed impressive responses on the interaction of MLD, Citrals, and ATRA as related to their impact on associated lung tissue pathologies.

Ovarian cancer is the leading cause of mortality among the gynecologic cancers and is the 5th most common cancer among women. Recent studies have indicated that antioxidant exposure may slow the progression in major neoplastic diseases. The objective of this study was to investigate the pathophysiological effects of Thymoquinone (TQ) and Epigallocatechin-3-gallate (EGCG) using the SK-OV-3 cell line as a model. A total of 72 wells were plated with (10^5) SK-OV-3 ovarian cancer cells according to standard lab protocols. Each group was subdivided into 4 groups of 6 wells each. Group 1 served as control and groups 2, 3, and 4 were treated with TQ (16 µM), EGCG (3 µg/ml), and TQ + EGCG, respectively. Biomarker and morphological evaluations were performed following standard lab techniques. The results of the study revealed: (1) there were no differences in protein levels for all time periods (p0.05); (2) an increase in nitric oxide following the administration of EGCG alone and in combination with TQ compared with TQ alone or untreated control cells with the difference being approximately three-fold higher and this difference was statistically different (p0.05) at 24, 48, 72 hours; (3) glutathione levels were not statistically different at all time periods (p0.05); and (4) the MDA levels showed no damage to the SK-OV-3 ovarian cancer cells. The results of this study provided the literature with more insights regarding manipulation of ovarian cancer behavior through potent antioxidants such as TQ and EGCG in culture.

There is less than a thirty percent survival rate for patients with a localized pancreatic tumor, and less than a ten percent survival rate for patients with metastases. Patients with pancreatic cancer often have altered glucose metabolism and are prescribed metformin which has been shown to reduce cancer cell proliferation. Metformin administered at doses ranging between 10-20 mM has been reported in the literature to induce AMPK signaling pathways which increase cellular apoptosis. Epigallacto-catechan (EGCG) is a polyphenolic antioxidant that has also been shown to increase the AMPK pathway that increases cellular apoptosis. The objective of this study was to investigate the effectiveness of EGCG with a clinical dose of metformin (10µM) in reducing the survival of a pancreatic like cell line in culture. PANC-1 cells were plated onto three 24 well plates at a density of 1 x 106 cells per well. The experimental design consisted of four equal groups: Group 1 served as the control and groups 2-4 were treated with metformin, (EGCG) or metformin and EGCG, respectively. Biochemical and morphological evaluations were conducted following standard lab protocols. Results of this study show 10µM of metformin was unable to alter cell growth or proliferation over a 72 hour period, while 50µM of EGCG alone or in combination with metformin were capable of reducing cell density and cellular protein levels at 48 and 72 hours following treatment. The results show EGCG induced changes in cellular morphology which are characteristic of apoptosis. Overall, additional studies are needed to determine the effects of EGCG on AMPK and ATM pathways that are responsible in normal cellular apoptotic processes.

Recent reports in the literature show an increase in the risk of heart related events in patients treated with tricyclic antidepressants. There is also evidence that serotonin reuptake inhibitors (SSRIs) are negatively associated with heart failure. The objective of our study is to determine if cardiomyocytes in culture can be used as a tool to mimic clinical scenarios and to evaluate therapeutic concentrations of SSRIs (fluoxetine) and antidiabetic (troglitazone) medication. Cardiomyocytes were grown in a tissue culture environment and challenged with therapeutic concentrations of SSRIs alone or a combination of SSRIs and antidiabetic drugs. Intracellular markers for stress and cytomorphometric analysis indicated SSRIs and SSRIs in combination with antidiabetic drugs negatively impact the health of the cardiomyocytes with time in culture. Analysis of the nuclear area and cytoplasmic changes are sensitive enough to use a cell-based model for determination of adverse effects associated with co-administration of drugs.

Macrophages and blood vessels are critical components in the biocompatibility and functionality of implantable ceramic materials used in drug delivery applications. The purpose of this study was to examine the correlation of macrophage and neovascularization by further defining their presence, relationship, and correlation in the fibrous tissue capsule of calcium phosphate (TCP) ceramic drug delivery systems. Sixteen animals in four experimental groups were implanted with one TCP bioceramic each. Group I animals were implanted with a TCP ceramic not containing a biologic (control group). Group II animals received the testosterone loaded TCP ceramic. Group III animals were implanted with the dihydrotestosterone loaded ceramic. Group IV animals received the androstenedione ceramic. At 90 days post-implantation, the animals were euthanized. Implants and fibrous tissue capsules were collected. Determination of macrophage populations and neovascularity was conducted microscopically following HE staining and aided by ImagePro digital analysis software. Androgens have varying effects on vascularity and macrophage populations. Overall, macrophage counts were highly and significantly correlated with vascularity (p0.05), particularly in Groups II, III, and IV. Correlations for Group I was not statistically significant. These findings suggest that presence of macrophages is be directly related to neovascularity, especially in the presence of exogenous androgens.

The objective of this investigation was to quantify and further elucidate the tissue-implant response in the fibrous tissue surrounding tricalcium phosphate (TCP), hydroxyapatite (HA), and aluminum calcium phosphate (ALCAP) implants when implanted subcutaneously. Sixteen animals in four experimental groups (n = 4/group) were implanted with one implant each: Group I (control, TCP), Group II (HA), and Group III (ALCAP). At 90 days post-implantation, the fibrous tissue surrounding the implants was harvested. Sections of stained fibrous tissue were evaluated for the presence of macrophages, fibrocytes, neutrophils, vascularity and thickness for all three groups using semi-automated quantitative methods. The analysis indicated Group III demonstrated a significantly higher number of neutrophils but fewer macrophages and blood vessels per high power field and had a substantially thinner fibrous tissue capsule thickness compared to Groups I and II (alpha=0.05). Group II elicited a greater response of fibroblasts compared to Groups I and III suggesting HA may provide a slightly higher degree of stability to the implant. In total, these findings suggest both TCP and HA behave similarly in vivo when compared to ALCAP and may be better choices for subcutaneous soft-tissue application compared to ALCAP.

It is well documented that Inflammatory cytokines such as IL-6 are thought to be mediators in the initiation of several organ injuries by inducing apoptosis and necrosis. Several reports have indic...

Both chronic and acute ethanol exposure have been shown to be cytotoxic and also to disrupt normal cell function or responses in a variety of cell types. Macrophage function has specifically been shown to be disrupted by chronic ethanol exposure by mechanisms that have not been elucidated. It is known that exposure of macrophages to lipopolysaccharide (LPS) from gram-negative bacteria will decrease the number of cells. Since increased exposure to endotoxin is often associated with chronic alcoholism, this may be one mechanism to account for loss of macrophages in alcoholic patients. The loss of macrophages, as a consequence of endotoxin treatment, appears to be linked to cell activation and, in particular, LPS-stimulated synthesis of nitric oxide which has been suggested to cause an increase in apoptosis. Ethanol also increases apoptosis in some cell types but, in general, ethanol inhibits activation of macrophages. Thus, the overall effect on cell numbers and cell proliferation elicited by treating macrophages concomitantly with ethanol and LPS depends on the balance between inhibiting LPS-mediated activation and the actions of ethanol. The interaction between ethanol and LPS was investigated in a macrophage cell line (RAW 264.7 cells) by measuring nitric oxide production and cell proliferation. A 24-h exposure to ethanol (100 mM) decreased [3H]-thymidine incorporation significantly. LPS treatment elicited a concentration-dependent decrease in [3H]-thymidine incorporation at LPS concentrations of 0.1 ng/ml to 1000 ng/ml and stimulated nitric oxide production at concentrations above 1 ng/ml. LPS-stimulated nitric oxide production was inhibited by ethanol (20 to 100 mM) and the nitric oxide synthesis inhibitor, N(G)Nitro-L-arginine methyl L-NAME) ester (100 and 500 microM). However, LPS-inhibited [3H]-thymidine incorporation was not be totally reversed by ethanol- or L-NAME-treatment. A direct correlation between nitric oxide production and inhibition of cell proliferation could not be demonstrated. However, it appears that ethanol and LPS do affect some common mechanism(s) in this cell line.

Osteonecrosis is a disease that is characterized by lesions of dead bone, most frequently detected in the subchondral bone of the convex side of the major diarthrodial joints (hips, knees, shoulders, and talus). High-dose corticosteroid therapy is one major risk factor for osteonecrosis. The pathological appearance of osteonecrosis of the femoral head, however, is fairly consistent regardless of the etiology. Depending on the stage of the disease, this includes evidence of bone marrow edema, lipocyte and bone cell necrosis, fibrosis, creeping substitution (new bone lying on dead bone), and the presence of osteoporosis [1]. Hemorrhage within the bone marrow compartment has also been observed in patient specimens from corticosteroid-associated osteonecrosis [2]. Previous investigators have suggested that corticosteroid-associated osteonecrosis has more rapid progression than other etiologies [1, 3]. The mechanisms involved in the development of osteonecrosis [ON] are difficult to explore from clinical samples as they provide a single snapshot at one time point subsequent to the onset of the disease, usually months after the onset of the disease when the symptoms first appear. While some investigators have used corticosteroid-associated animal models to evaluate different potential treatments [4–6], it is not clear whether the results can be extrapolated to the human condition. A better understanding of the pathophysiological mechanisms is needed.

Osteoporosis affects over ten million persons within the United States and is estimated to cost the healthcare system $18 billion dollars a year. Approximately 1.5 million persons will be diagnosed with an osteoporotic fracture and the epidemiological data reflects that prevalence of the osteoporotic fractures is four times more common than having a stroke. The current treatments strategies for osteoporosis are geared toward inhibiting the osteoclast cell resorption of bone, and not on the osteoblast bone formation. The use of demineralized bone matrix proteins (DBM) has been shown to be effective in healing osteoporotic bone fractures within a four week time period. Our goal was to deliver in a sustained manner DBM over an eight week period and compare bone strength and bone histology to osteoporotic untreated animals, osteoporotic animals given sustained delivery of physiological estrogen, as well as naïve control (animals with ovary intact). Our results showed estrogen administered in a sustained fashion was able to reverse the decline in bone strength and re-establish the bone quality similar to ovary intact controls. DBM administered in a sustained manner showed similar bone quality and strength to osteoporotic control animals. Administration of DBM to mature bone in a sustained fashion may be ineffective in inducing osteoblast function or reversing osteoclast activity. It is possible that DBM may be more effective on immature bone cells.

We describe the preliminary findings of seatbelt compliance among severely injured blunt trauma patients involved in motor vehicle crashes in Mississippi. Stratification of the sample size of 1,405 patients included obese versus the non-obese patients with sub-stratification of weight classes to include normal weight, overweight, obese and morbidly obese. An overview of the design of the study is included. The results demonstrate no significant difference between the numbers of restrained and unrestrained obese patients compared to their normal weight counterparts. Our findings suggest unrestrained patients regardless of weight class had higher ISS than restrained individuals. The data for Mississippi is similar to those reported nationally. Interestingly, we observed the injury severity scores in the restrained obese and morbidly obese patients were higher than the unrestrained motorists within the same weight cohort. This may reflect less movement within the vehicle resulting in less trauma.

Glucocorticoids have long been recognized to have beneficial effects in rheumatoid arthritis and asthma. Numerous clinical trials show the efficacy of short term low dose treatment to resolve inflammation. Despite the success of short term use, there is concern regarding chronic use of glucocorticoids because of the development of exogenous Cushing’s syndrome. Chronic variable stress models have detailed the effects of chronic stress exposure on body weight, plasma corticosteroid levels, ACTH levels, and adrenal weights, but limited studies detail the effects of the body systems induced by continuous exposure to glucocorticoids similar to that seen in exogenous Cushing’s syndrome. The present study uses a TCPL drug delivery system to administer corticosterone (CS) continuously in male and female animals for 24 days and evaluates long term chronic use effects on body weight, adrenal weight, and adrenal ultrastructure. Continuous release of CS resulted in slight decreases in body weight in both male and female rats and decreases in adrenal wet weight in the female rats. Ultrastructural changes were seen in the adrenal histology in both female and male rats. Male rat adrenal glands showed atrophy of the zona glomerulosa and hypertrophy of the adrenal medulla. Female rats showed disorganization of all zones within the adrenal gland and an increase in fat around the gland. The information is important for understanding physiological differences in males and females during stress. The continuous release of CS may provide insight into the pathology of exogenous Cushing’s syndrome.

IntroductionNeuropeptide Y (NPY) is a 36-amino acid neuropeptide that acts as a neurotransmitter in the brain and in the autonomic nervous system of humans. In the autonomic system it is produced m...

In an effort to increase the number of well trained minority healthcare professionals and basic science researchers, Jackson State University, (JSU, a historically black institution) in partnership with Hinds Community College (HCC, a 2-year college) and consultant biomedical researchers/healthcare professionals at the University of Mississippi Medical Center established a Bridges to the Baccalaureate Degree Program (BBDP). The purpose of the BBDP was to enhance HCC students transfer rates to 4 year institutions and to motivate trainees to seek Baccalaureate and advanced degrees in the biomedical and health sciences areas. The program utilized faculty and administrators at each institution in the planning and implementation of all programmatic aspects, including student selection, advisement procedures and program activities. HCC students (280) were recruited, 94.5 % of whom were African American, and trained in research laboratory methodologies, responsible conduct of research concepts, literature survey mechanisms, and scientific writing techniques during the academic year. Students engaged in specific individualized research projects during the summer and presented their research findings at local scientific seminars and professional meetings e.g., Mississippi Academy of Sciences, ABRCMS, FASEB, and the Endocrine Society. Sixty-five percent of students eligible to transfer actually transferred to Jackson State University and 8 other colleges and universities. Approximately 70% of the transfer students obtained Baccalaureate degrees and many received or are enrolled in masters and doctorate degree programs. HCC science faculty also received additional research training experiences and in 6 cases, initiated or completed terminal degrees in the sciences. In conclusion, it is clear that exposure to research training in the biomedical sciences can enhance community college students transfer rates and potential to seek advanced degrees.

Preliminary research has shown evidence of the presence of connective tissue growth factor CTGF in the tenosynovium of patients with carpal tunnel syndrome, a finding which supports the fibrotic pathophysiological progression of the disease. Connective tissue growth factor (CTGF) expression is regulated through the actions of two distinct molecular signals; transforming growth factor-beta (TGF-ß) and hypoxia inducible factor-1 alpha (HIF-1a). Mannose-6 phosphate is a natural inhibitor of TGF-ß and can also is converted to fructose 6 phosphate which we have shown is capable of reducing HIF-1 a. The goal of this experiment was to determine if mannose 6 phosphate is capable of reducing HIF-1a reducing both components of the CTGF pathway. Fibroblast cells were subjected to 5µM or 50µM concentration of either fructose 1,6 diphosphate (F6P) or mannose 6 phosphate (M6P) for a period of 24 hours in either ambient or hypoxic conditions. After the incubation period, cell viability, cell damage, morphology, and concentration of HIF-1a were determined. Cell numbers were reduced by approximately 50% in hypoxic conditions compared with ambient control. Intracellular glutathione concentration was increased significantly under hypoxic conditions compared with control. The concentration of reduced glutathione in both F6P and M6P were similar to ambient air values indicating a protection against oxidative stress. Hypoxia inducible factor-1 alpha was increased in cells under hypoxic conditions compared to base line levels in normoxic treated cells. Interestingly, only 5µM F6P was able to reduce HIF-1a back toward control normoxic values. The data suggest that the HIF-1a pathway leading to fibrosis is not the primary pathway for reductions in CTGF following MP6 treatments. This information is important in terms of developing compounds which decrease adhesion while not decreasing cell viability or impairing cellular function.

Mesenchymal stem cells (MSCs) have the capabilities to proliferate and differentiate into osteoblastic and chondrogenic lineages when stimulated with bone morphogenic proteins (BMPs). BMPs play a vital role in skeletal development. BMPs bind to their cell surface receptors on MSCs and send signals to the cell nucleus which results to the synthesis of macromolecules involved in cartilage and bone formation and then the mesenchymal cell differentiates into chondrocytes or osteoblasts. The objective of this study was to evaluate the effects of BMP-2, BMP-7, and BMP-13 on undifferentiated MSCs for cellular damage markers, alkaline phosphatase, and morphological changes at 24, 72, 120, and 168 hours of culture. MSC viability, proliferation, cellular damage, and cellular morphology were evaluated after each time point. As early as 48 hours MSCs treated with BMPs resulted in morphological changes, and increased cell numbers. At 120 and 168 hours BMP-13 resulted in morphological changes resembling chrondrocytes. It was concluded that BMPs have no adverse effects on proliferation and are non- toxic to undiffetentiated MSCs.