Cautionary tales in the interpretation of systematic reviews of therapy trials

This is the second in a series of articles emphasizing the cautions in the interpretation of health-care studies. Systematic reviews are presented as comprehensive, unbiased summaries of evidence and are often referred to by clinicians, guideline developers and health policy-makers. Their strengths and limitations, and how their results can be subject to bias and misinterpretation, are discussed.

Paracetamol [acetaminophen]-induced gastrotoxicity: Revealed by induced hyperacidity in combination with acute or chronic inflammation

Paracetamol is regarded as a relatively safe drug in the gastro-duodenal region of humans but recent epidemiological investigations have suggested that at high doses there may be an increased risk of ulcers and bleeding. To investigate the possibility that inflammatory conditions and gastric acidity may play a role in potentiating development of gastric mucosal injury from paracetamol in rats (as noted previously with various non-steroidal anti-inflammatory drugs) we studied the gastric irritant effects of paracetamol and some phenolic and non-phenolic analgesics and antipyretics in rats with adjuvant or collagen II induced arthritis or zymosan-induced paw inflammation and given 1.0 ml hydrochloric acid (HCl) 0.1 M and/or an i. p. injection of the cholinomimetic, acetyl-β-methyl choline chloride 5.0 mg/kg. Gastric lesions were determined 2 h after oral administration of 100 or 250 mg/kg paracetamol or at therapeutically effective doses of the phenolic or non-phenolic analgesics/antipyretics. The results showed that gastric mucosal injury occurred with all these agents when given to animals that received all treatments so indicating there is an adverse synergy of these three factors, namely: (i) intrinsic disease; (ii) hyperacidity; and (iii) vagal stimulation for rapidly promoting gastric damage, both in the fundic as well as the antral mucosa, for producing gastric damage by paracetamol, as well as the other agents. Removing one of these three predisposing factors effectively blunts/abolishes expression of this paracetamol-induced gastrotoxity in rats. These three factors, without paracetamol, did not cause significant acute gastropathy.

The fountain amacrine cells of the rabbit retina

We have characterized a distinctive type of bistratified amacrine cell in the rabbit retina at both the single cell and population levels. These cells correspond to the fountain amacrine cells recently identified by MacNeil and Masland (1998). The fountain cells can be distinguished in superfused retinal wholemounts labeled with nuclear dyes, thus enabling them to be targeted for intracellular injection with Neurobiotin. This revealed that the primary dendrites ascend steeply to sublamina b of the inner plexiform layer, where they form an irregular arbor at the border of strata 4 and 5. These dendrites then give rise to multiple varicose processes that descend obliquely to sublamina a, where they form a more extensive arbor in stratum 1. The fountain amacrine cells show strong homologous tracer coupling when injected with Neurobiotin, and this has enabled us to map their density distribution across the retina and to examine the dendritic relationships between neighboring cells. The fountain amacrine cells range in density from 90 to 360 cells/mm(2) and they account for 1.5% of the amacrine cells in the rabbit retina. The thick tapering dendrites in sublamina b form highly territorial arbors that tile the retina with minimal overlap, whereas the thin varicose processes intermingle in sublamina a. The fountain cells are immunopositive for gamma-aminobutyric acid and immunonegative for glycine. We further propose that these cells are homologous to the substance P-immunoreactive (SP-IR) amacrine cells in the cat retina and that they may account for a subset of the SP-IR amacrine cells in the rabbit retina.

Drug utilization evaluation of parenteral proton pump inhibitors

Current evidence supports parenteral infusion of proton pump inhibitors (PPI) after endoscopic treatment of bleeding peptic ulcers and such treatment seems reasonable where there is active bleeding or visible vessel on endoscopy. Parenteral boluses of PPI can be used in patients nil by mouth who cannot tolerate oral therapy. We sought to examine the appropriateness of parenteral PPI use. Drug utilisation evaluation was performed on 94 patients admitted to a 500 bed metropolitan hospital. 39 patients received continuous parenteral infusion of omeprazole (8 mg/ h) over a mean of 60 ± 29 h. 55 patients had parenteral boluses (40 mg bd) of omeprazole over a mean of 5 ± 4 days. Indications for PPI infusion (n = 39) were: major haemorrhage requiring transfusion (23), minor haemorrhage (8), dyspepsia (4) and others (4). 31 of the 39 patients on PPI infusion had upper gastrointestinal (GI) endoscopy. PPI infusion was commenced prior to endoscopy in 26 (84%) patients. 13 patients (33%) had active bleeding or visible non bleeding vessels at endoscopy. Only 11 patients (28%) had endoscopically treated peptic ulcers. Indications for parenteral PPI boluses (n = 55) included patients nil by mouth unable to take maintenance PPI orally (21), minor haemorrhage (8), peptic ulcer prophylaxis in seriously unwell (6), major haemorrhage (4), dyspepsia (2), postoprative period following peptic ulcer surgery (2) and others (12). Endoscopy was performed in 10 patients (18%) with only 1 endoscopically treated peptic ulcer. Our data suggest significant inappropriate use of parenteral PPI, which may be used for minor GI bleeding and dyspepsia and are typically commenced prior to endoscopy. These findings can explain the costly hospital expenditure on PPI.

Host-bacteria interactions : Host cell responses and bacterial pathogenesis

Helicobacter pylori colonizes the human stomach, where it causes gastritis that may develop into peptic ulcer disease or cancer when left untreated. Neisseria gonorrhoeae colonizes the urogenital tract and causes the sexually transmitted disease gonorrhea. In contrast, Lactobacillus species are part of the human microbiota, which is the resident microbial community, and are considered to be beneficial for health. The first host cell types that bacteria encounter when they enter the body are epithelial cells, which form the border between the inside and the outside, and macrophages, which are immune cells that engulf unwanted material.       The focus of this thesis has been the interaction between the host and bacteria, aiming to increase our knowledge of the molecular mechanisms that underlie the host responses and their effects on bacterial pathogenicity. Understanding the interactions between bacteria and the host will hopefully enable the development of new strategies for the treatment of infectious disease. In paper I, we investigated the effect of N. gonorrhoeae on the growth factor amphiregulin in cervical epithelial cells and found that the processing and release of amphiregulin changes upon infection. In paper II, we examined the expression of the transcription factor early growth response-1 (EGR1) in epithelial cells during bacterial colonization. We demonstrated that EGR1 is rapidly upregulated by many different bacteria. This upregulation is independent of the pathogenicity, Gram-staining type and level of adherence of the bacteria, but generally requires viable bacteria and contact with the host cell. The induction of EGR1 is mediated primarily by signaling through EGFR, ERK1/2 and β1-integrins. In paper III, we described the interactions of the uncharacterized protein JHP0290, which is secreted by H. pylori, with host cells. JHP0290 is able to bind to several cell types and induces apoptosis and TNF release in macrophages. For both of these responses, signaling through Src family kinases and ERK is essential. Apoptosis is partially mediated by TNF release. Finally, in paper IV, we showed that certain Lactobacillus strains can reduce the colonization of H. pylori on gastric epithelial cells. Lactobacilli decrease the gene expression of SabA and thereby inhibit the binding mediated by this adhesin.

Apoptosis induction in gastric mucous cells in vitro:lesser potency of Helicobacter pylori than Escherichia coli lipopolysaccharide, but positive interaction with ibuprofen

Non-steroidal anti-inflammatory drugs (NSAIDs) cause peptic ulcer disease, but whether they interact with Helicobacter pylori to promote damage is controversial. Moreover, the reported induction of apoptosis in gastric cells by H. pylori lipopolysaccharide (LPS) (10-9 g /ml) contrasts with studies showing low immunological potency of this LPS. Therefore, the effects of LPS from H. pylori NCTC 11637 and Escherichia coli 0111:B4 on apoptosis in a primary culture of guinea-pig gastric mucous cells were investigated in the presence and absence of the NSAID, ibuprofen. Cell loss was estimated by a crystal violet assay, and apoptosis determined from caspase activity and from condensation and fragmentation of nuclei. Exposure to E. coli LPS for 24 h caused cell loss and enhanced apoptotic activity at concentrations ≥ 10-9 g/ml, but similar effects were only obtained with H. pylori LPS at concentrations ≥10-6 g/ml. Although ibuprofen (250 μM) caused cell loss and apoptosis, addition of either E. coli or H. pylori LPSs further enhanced these effects. In conclusion, LPS and ibuprofen interact to enhance gastric cell loss and apoptosis. In such interactions, E. coli LPS is more potent than that of H. pylori. The low potency of H. pylori LPS may contribute to a chronic low-grade gastritis that can be enhanced by the use of NSAIDs. © W. S. Maney & Son Ltd.

The effects of advanced practice nurses (APNs) as intensivists in a surgical intensive care unit (SICU) on patient outcomes, healthcare charges, and apn intensivist services in the SICU

Intensive Care Units (ICUs) account for over 10 percent of all US hospital beds, have over 4.4 million patient admissions yearly, approximately 360,000 deaths, and account for close to 30% of acute care hospital costs. The need for critical care services has increased due to an aging population and medical advances that extend life. The result is efforts to improve patient outcomes, optimize financial performance, and implement models of ICU care that enhance quality of care and reduce health care costs. This retrospective chart review study examined the dose effect of APN Intensivists in a surgical intensive care unit (SICU) on differences in patient outcomes, healthcare charges, SICU length of stay, charges for APN intensivist services, and frequency of APNs special initiatives when the SICU was staffed by differing levels of APN Intensivist staffing over four time periods (T1-T4) between 2009 and 2011. The sample consisted of 816 randomly selected (204 per T1-T4) patient chart data. Study findings indicated reported ventilator associated pneumonia (VAP) rates, ventilator days, catheter days and catheter associated urinary tract infection (CAUTI) rates increased at T4 (when there was the lowest number of APN Intensivists), and there was increased pressure ulcer incidence in first two quarters of T4. There was no statistically significant difference in post-surgical glycemic control (M = 142.84, SD = 40.00), t (223) = 1.40, p = .17, and no statistically significant difference in the SICU length of stay among the time-periods (M = 3.27, SD = 3.32), t (202) = 1.02, p = .31. Charges for APN services increased over the 4 time periods from $11,268 at T1 to $51,727 at T4 when a system to capture APN billing was put into place. The number of new APN initiatives declined in T4 as the number of APN Intensivists declined. Study results suggest a dose effect of APN Intensivists on important patient health outcomes and on the number of APNs initiatives to prevent health complications in the SICU. ^

Systematic Monitoring of Wound Healing Using a Hand-held Near-Infrared Optical Scanner

According to the American Podiatric Medical Association, about 15 percent of the patients with diabetes would develop a diabetic foot ulcer. Furthermore, foot ulcerations leads to 85 percent of the diabetes-related amputations. Foot ulcers are caused due to a combination of factors, such as lack of feeling in the foot, poor circulation, foot deformities and the duration of the diabetes. To date, the wounds are inspected visually to monitor the wound healing, without any objective imaging approach to look before the wound’s surface. Herein, a non-contact, portable handheld optical device was developed at the Optical Imaging Laboratory as an objective approach to monitor wound healing in foot ulcer. This near-infrared optical technology is non-radiative, safe and fast in imaging large wounds on patients. The FIU IRB-approved study will involve subjects that have been diagnosed with diabetes by a physician and who have developed foot ulcers. Currently, in-vivo imaging studies are carried out every week on diabetic patients with foot ulcers at two clinical sites in Miami. Near-infrared images of the wound are captured on subjects every week and the data is processed using customdeveloped Matlab-based image processing tools. The optical contrast of the wound to its peripheries and the wound size are analyzed and compared from the NIR and white light images during the weekly systematic imaging of wound healing.

Avaliação da atividade anti-Helicobacter pylori e citotóxica in vitro de extratos orgânicos obtidos das folhas de Encholirium spectabile e Syzygium cumini

Helicobacter pylori is a spiral, Gram negative, mobile, and microaerophilic bacteria recognized as a major cause of gastritis, ulcer, gastric cancer, and gastric low grade, B cell, mucosa – associated lymphoid tissue (MALT) lymphoma, constituting an important microorganism in medical microbiology. Its importance comes from the difficulty of treatment because the requirement of multiple drugs use, besides the increasing emergence of resistant and multiresistant strains to antibiotics used in th e clinic. In order to expand safe and effective therapeutic options , chemical studies on medicinal plants by obtaining extracts, fractions, isolated compounds or essential oils with some biological activity has been intensified . Given the above, the objective was to evaluate the inhi bitory activity of organic extracts derived from Syzygium cumini and Encholirium spectabile, with antiulcer history, and the essential oil, obtained from S. cumini, against H. pylori (ATCC 43504) by the disk diffusion method, for qualitative evaluation, an d determination of minimum inhibitory concentration (MIC) using the broth microdilution method, for quantitative analysis. Also was evaluated the extracts in vitro toxicity by a hemolytic assay using sheep red blood cells, and VERO and HeLa cells using the MTT assay to analyze cell viability. The extracts of both plant used in antimicrobial assays did not inhibit bacterial growth, however the essential oil of S. cumini (SCFO) proved effective, showing MIC value of 205 μg/mL (0.024 % dilution of the original oil). In the hemolytic assay, the same oil shows moderate toxicity, by promote 25% hemolysis at 1000 μg/mL. Regarding the cytotoxicity in cell culture, the SCFO, at 260 μg/mL, affected the cell viability around 80% of HeLa and 50% of VERO cells. So the oi l obtained from S. cumini leaves has antimicrobial activity against H. pylori and cytotoxicity potential, suggesting a source of new molecule drug candidates, since new stages of toxicity in vitro and in vivo, as well, chemical characterization be evaluate d. Moreover, the development of a prospective drug delivery system can result in a prototype to be used in preclinical tests.

Autoeficácia e qualidade de vida de pessoas com úlcera venosa

Venous ulcers (UV) are the result of deep venous insufficiency or obstruction leading to venous hypertension in the lower limbs and lesions. Self-efficacy is the belief in the ability to successfully perform a given task or exhibit behavior that leads to a desirable outcome. Nursing needs to know and explore the influence of self-efficacy on quality of life (QOL) of people with UV, seeking to exercise holistic care. Thus, this study aimed to analyze the correlation of self-efficacy for pain control and functionality with the QOL of people with UV in primary health care. It is a cross-sectional, analytical, quantitative study with people with UV in family health strategy and mixed units in Natal / RN. We used the instruments: sociodemographic and health questionnaire, domains self-efficacy for pain control and self-efficacy for functionality of Scale of Self-Efficacy for Chronic Pain (SFCD) and the Charing Cross Venous Ulcer Questionnaire (CCVUQ). The sample included 101 people in the self-efficacy scale for functionality and 89 in self-efficacy for pain, for twelve patients reported no pain at the time of collection, and therefore were excluded from the application of the scale of selfefficacy for pain. The project was approved by the ethics committee of the Federal University of Rio Grande do Norte (CAAE No. 07556312.0.0000.5537), serving Resolution 466/12. Women predominated (66.3%), elderly (61.4%), married or in a stable relationship (63.4%), low income (90.1%) and education (85.1%), inactive (75.2%), associated chronic diseases (60.4%), more than six hours of sleep / day (82.2%), non-drinkers / smokers (80.2%), chronic injury (73.3%) and moderate to severe pain (76.2%). Self-efficacy for pain (mean 67.3, SD 26.6) was less committed to the self-efficacy for functionality (mean 59.4 SD 25.9), with statistical difference (pvalue = 0.011). No significant associations were found between self-efficacy for pain control and functionality with the sociodemographic and health characteristics. When considering the total mean CCVUQ (mean 52.1, SD 16.6), QOL of respondents tended to worsen, with the aesthetic domain the most committed (mean 57.6, SD 24.0), followed by emotional state (mean 57.0, SD 25.7), social interaction (mean 48.4, SD 21.4) and household activities (mean 43.6, SD 23.3) . We found negative and significant correlations between self-efficacy for pain and CCVUQ total score (r = -0,324; p = 0,001), the social interaction domain (r = -0,278; p = 0,008), household activities (r = - 0,285; p = 0,007) and state emotional (r = -0,247; p = 0,019). Likewise, between selfefficacy for functionality and the CCVUQ total score (r = -0,553; p < 0,001), the social interaction domain (r = -0,553; p < 0,001), household activities (r = -0,594; p < 0,001) and emotional status (r = -0,259; p = 0,009). The aesthetic domain showed negative correlation but weak and not significant with self-efficacy for pain (r = -0, 155; p = 0,147) and functionality (r = -0,189; p = 0,058). It became evident the correlation between self-efficacy for pain control and functionality and the domains social interaction, household activities and emotional state, the quality of life of people with UV

História oral de vida de pessoas com úlcera venosa nos serviços de atenção primária à saúde

The Chronic Venous insufficiency is characterized as a set of physical changes including how most serious complication of venous ulcers, characterized by irregular and progressive loss of continuity of the skin. The occurrence of venous ulcers in people with chronic venous insufficiency generates dependence on them with health services, with long-term treatments that cause limitations and high-impact changes, affecting their quality of life, affecting the physical, psychological, social, cultural and spiritual as an important public health problem. This study aimed to describe the experience of having a venous ulcer, in the scenario of primary health care services to Health, which includes Primary Care Units and Family Health Strategy in the city of Natal / RN, based on the life histories of users. This is a qualitative study, exploratory and descriptive, with the Oral History of Life as a methodological framework. From the ponto zero was the recruitment of participants who formed the network, totaling six employees, of both sexes and aged between 57 and 79 years. After approval by the Research Ethics Committee - UFRN under the Protocol 653 788/2014 and CAAE 30408014.0.0000.5537 was held data collection, between the months of July and August, through interviews, using identification and characterization of the instrument employees and open questions. Interviews were recorded, transcribed, transcriadas and returned to employees for a conference. The narratives were subjected to Content thematic analysis technique, according to Bardin, allowing the construction of three themes that encompass categories, namely: Axis I - Perspectives on the changes: the impact wound in social relations (changes with ulcer venous, venous ulcer and social and family relationships); Axis II - Brands in body and soul: the story of being hurt (conceptions of the body injured; therapeutic itinerary in primary care services); and Axis III - Reconstruction of being hurt: coping mechanisms (redefinition of the wounded body, resilience to chronic wound). The impact of having a chronic venous ulcer generates impact of physical, psychological and social order. As aspects related to changes after the appearance of venous ulcers, survey participants reported the presence of pain, physical limitations, psychological distress, social and emotional isolation, incapacity, aesthetic discomfort and dependency on health services; the family was the aspect thatshowed no significant change after the occurrence of wound for most participants, an ally in the therapeutic process as a support network. The redefinition of the body and the wound are the main coping mechanism of chronic condition. The services in the Primary Care Network play a fundamental role in the rehabilitation of patients with venous ulcers, although there are difficulties in accessing appropriate treatment and need for expanded services, with permanent professional training of health teams and providing the resources managers to strengthen the comprehensive care of people with venous ulcers in Health Primary Care.

Obtenção e caracterização de sistemas particulados de quitosana para liberação gástrica de amoxicilina

The infection caused by Helicobacter pylori (H. pylori) is associated with gastroduodenal inflammation can lead to the development of gastritis, gastric or duodenal ulcer and gastric cancer (type 1 carcinogen for stomach cancer). Amoxicillin is used as first-line therapy in the treatment of H. pylori associated to metronidazole or clarithromycin, and a proton pump inhibitor. However, the scheme is not fully effective due to inadequate accumulation of antibiotics in gastric tissue, inadequate efficacy of ecological niche of H. pylori, and other factors. In this context, this study aimed to obtaining and characterization of particulate systems gastrorretentivos chitosan - amoxicillin aiming its use for treatment of H. pylori infections. The particles were obtained by the coacervation method / precipitation using sodium sulfate as precipitating agent and crosslinking and two techniques: addition of amoxicillin during preparation in a single step and the sorption particles prior to amoxycillin prepared by coacervation / precipitation and spray drying. The physicochemical characterization of the particles was performed by SEM, FTIR, DSC, TG and XRD. The in vitro release profile of amoxycillin free and incorporated in the particles was obtained in 0.1 N HCl (pH = 1.2). The particles have higher encapsulation efficiency to 80% spherical shape with interconnected particles or adhered to each other, the nanometric diameter to the systems obtained by coacervation / precipitation and fine for the particles obtained by spray drying. The characterization by FTIR, DSC and XRD showed that the drug was incorporated into the nanoparticles dispersed in the polymeric matrix. Thermal analysis (TG and DSC) indicated that encapsulation provides greater heat stability to the drug. Amoxicillin encapsulated in nanoparticles had slower release compared to free drug. The particles showed release profile with a faster initial stage (burst effect) reaching a maximum at 30 minutes 35% of amoxicillin for the system in 1: 1 ratio relative to the polymer and 80% for the system in the ratio 2: 1. Although simple and provide high encapsulation efficiency of amoxicillin, the process of coacervation, precipitation in one step using sodium sulfate as precipitant / cross-linker must be optimized in order to adjust the release kinetics according to the intended application.

Avaliação dos efeitos tóxicos in vitro e in vivo do extrato hidroetanólico dos frutos de Genipa americana L. (Rubiaceae) em camundongos Swiss

The therapeutic use of medicinal plants has contributed since antiquity in a beneficial way for health. However, many species lacks of scientific evidence which provide basis for their use in therapeutic practice. In this context is the Genipa americana L. species (Rubiaceae), popularly known as jenipapo and used to treat syfilis, ulcer and hemorrhagic disturbs. It's also used against bruising, as tonic and as aphrodisiac. Due this species lacks toxicological studies, the aim of this study was to evaluate the toxicity in vivo (acute and sub-chronic toxicity) and in vitro (cytotoxicity) of the hydroethanolic extract from G. americana fruits. The hydroethanolic extract of G. americana fruits was prepared by maceration. A preliminary phytochemical analysis was performed to assess the presence of secondary metabolites in the extract. The cytotoxicity study of the extract (0.1, 1.0, 10, 100 and 1000 mg / 100 ul) were performed against normal cells (3T3) and tumor (786-0, HepG2 and B16), analyzed by the MTT assay. To evaluate the acute (single dose of 2000 mg / Kg) and subchronic (100, 500 and 1000 mg / kg for 30 days) toxicity Swiss mice of both sexes were used. At the end of the experiment, blood samples and organs were collected for analysis. Data between groups were compared by t test or ANOVA with Dunnett's post-test with 5% significance level. The phytochemical study of the extracts mainly indicated the presence of iridoids. Results for cytotoxicity tests showed up to 70% inhibition of B16 cell line at a dose of 1000 mg / 100 ul, and up to 29% inhibition of 786-0 at a dose of 10 ug / 100 ul. The extract did not cause death in 3T3 and HepG2 cells. During the in vivo assays, there were no animal deaths. Analysis of blood samples revealed that the animals submitted to the evaluation of acute toxicity had changes in AST and ALT, and that the animals evaluated for subchronic toxicity showed changes in the relative wet weight of the kidney and plasma urea concentration. No differences were observed between groups on histopathological evaluation of the collected organs. Despite the changes found in the in vivo toxicity tests, using the criteria described by the OECD Guidelines, it is suggested that the hydroethanolic extract of the fruits of the G. americana is classified as low toxicity. The cytotoxicity of the extract suggests that they have potential against melanoma cell lines (B16).

Avaliação dos efeitos tóxicos in vitro e in vivo do extrato hidroetanólico dos frutos de Genipa americana L. (Rubiaceae) em camundongos Swiss

The therapeutic use of medicinal plants has contributed since antiquity in a beneficial way for health. However, many species lacks of scientific evidence which provide basis for their use in therapeutic practice. In this context is the Genipa americana L. species (Rubiaceae), popularly known as jenipapo and used to treat syfilis, ulcer and hemorrhagic disturbs. It's also used against bruising, as tonic and as aphrodisiac. Due this species lacks toxicological studies, the aim of this study was to evaluate the toxicity in vivo (acute and sub-chronic toxicity) and in vitro (cytotoxicity) of the hydroethanolic extract from G. americana fruits. The hydroethanolic extract of G. americana fruits was prepared by maceration. A preliminary phytochemical analysis was performed to assess the presence of secondary metabolites in the extract. The cytotoxicity study of the extract (0.1, 1.0, 10, 100 and 1000 mg / 100 ul) were performed against normal cells (3T3) and tumor (786-0, HepG2 and B16), analyzed by the MTT assay. To evaluate the acute (single dose of 2000 mg / Kg) and subchronic (100, 500 and 1000 mg / kg for 30 days) toxicity Swiss mice of both sexes were used. At the end of the experiment, blood samples and organs were collected for analysis. Data between groups were compared by t test or ANOVA with Dunnett's post-test with 5% significance level. The phytochemical study of the extracts mainly indicated the presence of iridoids. Results for cytotoxicity tests showed up to 70% inhibition of B16 cell line at a dose of 1000 mg / 100 ul, and up to 29% inhibition of 786-0 at a dose of 10 ug / 100 ul. The extract did not cause death in 3T3 and HepG2 cells. During the in vivo assays, there were no animal deaths. Analysis of blood samples revealed that the animals submitted to the evaluation of acute toxicity had changes in AST and ALT, and that the animals evaluated for subchronic toxicity showed changes in the relative wet weight of the kidney and plasma urea concentration. No differences were observed between groups on histopathological evaluation of the collected organs. Despite the changes found in the in vivo toxicity tests, using the criteria described by the OECD Guidelines, it is suggested that the hydroethanolic extract of the fruits of the G. americana is classified as low toxicity. The cytotoxicity of the extract suggests that they have potential against melanoma cell lines (B16).

RF MIMO Systems for Wide-Area Indoor Human Motion Monitoring

Human motion monitoring is an important function in numerous applications. In this dissertation, two systems for monitoring motions of multiple human targets in wide-area indoor environments are discussed, both of which use radio frequency (RF) signals to detect, localize, and classify different types of human motion. In the first system, a coherent monostatic multiple-input multiple-output (MIMO) array is used, and a joint spatial-temporal adaptive processing method is developed to resolve micro-Doppler signatures at each location in a wide-area for motion mapping. The downranges are obtained by estimating time-delays from the targets, and the crossranges are obtained by coherently filtering array spatial signals. Motion classification is then applied to each target based on micro-Doppler analysis. In the second system, multiple noncoherent multistatic transmitters (Tx's) and receivers (Rx's) are distributed in a wide-area, and motion mapping is achieved by noncoherently combining bistatic range profiles from multiple Tx-Rx pairs. Also, motion classification is applied to each target by noncoherently combining bistatic micro-Doppler signatures from multiple Tx-Rx pairs. For both systems, simulation and real data results are shown to demonstrate the ability of the proposed methods for monitoring patient repositioning activities for pressure ulcer prevention.