Orientadores: Edgard Ferro Collares, Alba Regina Monteiro Souza Brito / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-05T21:01:46Z (GMT). No. of bitstreams: 1 Vinagre_AdrianaMendes_M.pdf: 520546 bytes, checksum: 8639e020093258b50bba40d8d83f839c (MD5) Previous issue date: 2005 / Resumo: A úlcera péptica acomete cerca de 10% da população mundial; inseridos dentro dessa porcentagem estão milhares de brasileiros. Essa patologia é causada por um desbalanço entre os mecanismos protetores e agressores da mucosa, e é resultado da associação de diversos fatores agressores endógenos (ácido, pepsina e bile), fatores exógenos predisponentes às condições de vida (estresse, fumo, álcool, uso continuo de drogas antiflamatórias não esteróides, ingestão de determinados alimentos e a presença do Helicobacter pylori) e a predisposição genética. Atualmente, as terapêuticas utilizadas no tratamento das lesões são: antiácidos, anticolinérgicos, antagonistas de receptores H2 para histamina, inibidores da bomba de próton, antibióticos e mais raramente alguns procedimentos cirúrgicos. A aplicação de qualquer esquema terapêutico com emprego de uma ou mais destas drogas ou procedimento cirúrgico pode ocasionar alguns efeitos colaterais e não obrigatoriamente é eficaz. A utilização de plantas medicinais no tratamento de doenças vem se desenvolvendo na última década. Algumas plantas têm atividade antiulcerogênica. Há evidências que a alga Chlorella vulgaris pode modificar a resposta imune celular, tem atividade antitumoral, antimetastática e antiulcerogênica. O objetivo do presente estudo foi avaliar a atividade antiulcerogênica da alga Chlorella vulgaris em modelos agudos e um modelo crônico de indução de úlceras. Ratos Wistar foram utilizados para determinação do esvaziamento gástrico (EG) e modelos de úlcera induzida por etanol e ácido acético, enquanto camundongos swiss foram utilizados para os modelos de úlcera através de ligadura do piloro e piroxicam. Para avaliar o efeito sobre o esvaziamento gástrico (EG) do extrato de Chlorella vulgaris (ECV) foi utilizada uma refeição de prova (RP) liquida com extrato nas concentrações de 50mg/mL e 100mg/mL do ECV. Para o estudo dos modelos agudos de ligadura do piloro, etanol e piroxicam e do modelo crônico, foram utilizadas as doses de 250, 500 e 1000mg/kg de ECV para a prevenção e o tratamento das lesões. No modelo crônico também foi utilizada a fração acetato obtida do ECV na dose de 5mg/100g e foi dosada a quantidade de fator de crescimento epidermal (EGF) produzido na região da úlcera. O estudo da toxicidade do ECV foi realizado através da medida de ganho de peso dos ratos e peso dos órgãos como rins, pulmões, fígado e coração, visto que os primeiros sinais da toxicidade dada por um extrato é a perda de peso corporal e dos órgãos.O ECV, nas concentrações empregadas, não interferiu no EG quando preparado como uma RP liquida em comparação com o veículo (água). O extrato não alterou nenhum dos parâmetros bioquímicos como pH, quantidade de H+ e peso do suco gástrico, no modelo de ligadura do piloro. O ECV não preveniu a formação de úlceras no modelo de piroxican, mas evitou a formação de lesões causadas por etanol nas doses de 500 e 1000 mg/kg. Esse efeito desapareceu quando o etanol foi empregado duas horas após o pré-tratamento com ECV na dose de 1000 mg/kg. No modelo de úlcera crônica o ECV, nas doses de 500 e 1000 mg/kg, foi capaz de diminuir significativamente as lesões causadas pelo ácido acético, não alterando no entanto, a quantidade de EGF produzida na zona de cicatrização, quando comparados ao controle água. Além disso, o tratamento prolongado com o ECV na dose de 500 mg/kg alterou significativamente a evolução do ganho de peso desses animais. Em conclusão, o ECV, como complemento alimentar, pode ser uma alternativa no tratamento da úlcera péptica gástrica / Abstract: About 10%of the world¿s population suffer from peptic ulcer, within this percentage we find thousands of Brazilians. This pathology is caused by an unbalance between the protection and attack mechanisms of the stomach lining, and is the result of the association of various endogenous attack factors (pepsin, acid, bile), exogenous factors pertaining to life style (stress, smoking, alcohol intake, continuous use of non-steroidal anti-inflammatory drugs, ingestion of certain types of food and the presence of Helicobacter Pylori) and genetic predisposition. Nowadays, the therapeutic methods used for the treatment of the lesions are: Anti-acids, anti-cholinergic, antagonist H2 receptors for histamine, proton bombs; certain surgical procedures are also applied, though much less frequently. Any therapeutic method that involves the use of one or more of the drugs and/or procedures above mentioned may cause some side effects and is not necessarily effective. The use of medicinal plants in the treatment of diseases has been developing over the past decade. Some plants have an anti-ulcer activity. There is evidence that the Chlorella vulgaris algae may modify cellular immune response, and there is also evidence to its anti-tumor, anti-metastasis, anti-ulcer activity. The objective of this present study was to evaluate the anti-ulcer activity of the Chlorella vulgaris algae acute models of ulcer induction and also in one chronic model of ulcer induction. Wistar rats were used to determine gastric emptying (GE) and in models of ulcer induced by ethanol and acetic acid, while swiss mice were used for the piloro ligature and piroxicam ulcer induction models. In order to evaluate the effect of the Chlorella vulgaris extract (ECV) on gastric emptying (GE) a liquid proof meal (PM) with the extract in the concentration of 50mg/l and 100mg/l was usedIn the study of the acute piloro ligature, ethanol and piroxicam models, and in the chronic model, dosages of 250, 500 and 1000mg/kg of ECV were used in the prevention and treatment of the lesions. In the chronic model the fraction of acetate obtained from the ECV in the dosage of 5mg/100g was also used, and the amount of epidermal growth factor (EGF) produced in the region of the ulcer was measured. The toxicity study of the ECV was done by measuring the weight gain of the rats and the weight of their organs i.e. kidneys, lungs, liver, and heart, once the first signs of toxicity by an extract are loss of body and organ weight. The ECV, in the concentration used, did not interfere with the GE when prepared as a liquid PM in comparison to the vehicle (water). The extract did not alter any of the biochemical parameters such as pH, amount of H+ and weight of the gastric juice in the piloro ligature model. The ECV did not prevent the formation of ulcer in the piroxicam model, but it prevented the formation of lesions caused by ethanol in the dosage of 500 and 1000mg/kg. This effect disappeared when ethanol was ministered two hours after the pre-treatment with ECV in the dosage of 1000mg/kg. The chronic ulcer induction model the ECV, in the dosage of 500 and 1000mg/kg, was able to significantly lessen the lesions caused by acetic acid, not altering, however, the amount of EGF produced in the scar tissue area when compared to the water control. Furthermore, the long-term treatment with ECV in the dosage of 500mg/kg significantly altered the evolution of weight gain of these animals. In conclusion, the ECV, as a dietary complement, may be an alternative in the treatment of gastric peptic ulcer / Mestrado / Fisiologia / Mestre em Biologia Funcional e Molecular

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / O hidroxicitronelal à um composto amplamente usado como fragrÃncia em cosmÃticos. Este composto pode ser obtido a partir da semi-sÃntese do citronelal, um terpeno isolado do Ãleo essencial de citronela (Cymbopogon marginatus) ou de cidreira (Melissa officinalis), e tambÃm vÃrias outras plantas. O objetivo deste estudo à demonstrar a atividade gastroprotetora do hidroxicitronelal em modelos de lesÃo gÃstrica aguda. A manipulaÃÃo dos animais e os protocolos experimentais foram registrados no Comità de Ãtica Institucional (CEPA) sob o nÃmero 052/2011. Foram utilizados camundongos swiss, que foram divididos em grupos de 8 (n = 8), e foram submetidos a um perÃodo de jejum de 16h, entÃo foram tratados com HC nas doses de 0.5; 2.5 e 12,5 mg/Kg ou NAC (750 mg/Kg). ApÃs 30 minutos os animais receberam 0,2 ml de etanol absoluto v.o. E apÃs 30 min, os animais foram sacrificados, os estÃmagos removidos e analisados para determinaÃÃo do Ãndice de lesÃo ou feito homogenatos para a dosagem de GSH (glutationa reduzida). A fim de se investigar o envolvimento das prostaglandinas, NO e dos canais de potÃssio, antes do tratamento com HC os animais receberam L-NAME(20mg/Kg) e/ou L-arginina(600mg/Kg), indometacina (10mg/Kg) e/ou misoprostol(0.03Âg/Kg), Glibenclamida(5mg/Kg) e/ou DiazÃxido(3mg/Kg). Para investigar a participaÃÃo dos receptores TRPV1 , os animais receberam capsaicina(0,3mg/Kg) e/ou capsazepina(5mg/Kg). No modelo de Ãlcera gÃstrica induzida por AINEs, os animais foram tratados com HC (12.5; 50 e 200 mg/Kg) ou Cimetidina (100 mg/Kg) 30 min antes do tratamento com indometacina (60 mg/Kg), e depois de 6h os animais foram sacrificados, os estÃmagos removidos e analisados sob o critÃrio de escores de lesÃo. No modelo de lesÃo por etanol, HC nas doses de 0,5; 2.5 e 12 mg/Kg foi capaz de inibir a lesÃo em 31; 53 e 69% respectivamente. HC tambÃm recuperou os nÃveis de GSH na mucosa em 31.19% quando comparados com o grupo lesÃo. L-NAME, Glibenclamida e Indometacina foram capazes de reverter o efeito de HC, demonstrando o envolvimento das Prostaglandinas, NO e dos canais de potÃssio, em seu mecanismo de aÃÃo. Capsazepina foi inefetiva em reverter o efeito de HC, assim excluindo o possÃvel envolvimento dos receptores TRPV1. No modelo de lesÃo por AINEs, HC nas doses testadas reduziu os escores de lesÃo em 28.8, 56.3, e 84.1% respectivamente. Podemos concluir que HC possui uma atividade farmacolÃgica gastroprotetora sobre a mucosa do estÃmago. Essa proteÃÃo parece ser mediada em parte pela modulaÃÃo de Prostaglandina/NO/ KATP, que à de papel fundamental na manutenÃÃo do fluxo sanguÃneo e na defesa da mucosa gÃstrica. / The hydroxycitronellal is a compound widely used as fragrance in cosmetics. This compound can be obtained by semi-synthesis from citronellal, a terpenoid isolated from essential oil of citronella (Cymbopogon marginatus) or Balm (Melissa officinalis), and also found in other plants. The aim of this study is to demonstrate the gastroprotective of hydroxycitronellal in gastric ulcer models. Animal handling and experimental protocols were registered on the Institutional Ethics Committee (CEPA) under number 052/2011. Swiss mice were used, were divided into groups of 8 (n = 8), and undergo fasting of 16h, then were treated with HC in doses 0.5; 2.5 and 12,5 mg/Kg or NAC (750 mg/Kg). After 30 min they received 0, 2 ml of absolute ethanol per oral and after 30 min, the animals were sacrificed and stomachs removed and analyzed the lesion index and dosage of GSH (reduced glutathione). In order to investigate the involvement of prostaglandins, NO and potassium channels, before treatment with HC animals received L-NAME (20mg/Kg) or L-arginine (600mg/Kg), indomethacin (10mg/Kg) or misoprostol (0.03Âg/Kg), Glibenclamide (5mg/Kg) or Diazoxide (3mg/Kg). To investigate the participation of TRPV1 receptors, animals received capsaicin (0,3mg/Kg) or capsazepina (5mg/Kg). In the model of injury by NSAIDâs, the animals were treated with HC (12.5; 50 and 200 mg/Kg) or Cimetidine (100 mg/Kg) 30 min before treatment with indomethacin (60 mg/Kg), and after 6h animals were sacrificed and stomachs removed and examined under-rated scores. In model of injury by ethanol, HC at the doses 0,5; 2.5 and 12 mg/Kg was able to prevent injury in 31.0; 52.9 and 69.3% respectively. HC also restored the GSH levels in mucosa in 31.19% compared to the ethanol group. LNAME, Glibenclamide and Indometacin were able to reverse the protective effect of HC, demonstrating the involvement of Prostaglandins, NO and potassium channels in its mechanism of action. Capsazepine was unable to reverse the effect of HC, thus excluding a possible involvement of TRPV1 receptors. In the model of injury by NSAIDâs, HC in tested doses reduces the injury scores in 28.8, 56.3, and 84.1%respectively. We can conclude that the HC has pharmacological activity with gastroprotetor effect in the gastric mucosa. This protection appears to be mediated in part by modulation of Prostaglandin/NO/KATP, which is of great importance in mucosal defense and in maintaining blood flow to the stomach.

Orientadores: Rodney Alexandre Ferreira Rodrigues, Mary Ann Foglio, João Ernesto de Carvalho / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-26T07:27:17Z (GMT). No. of bitstreams: 1 Iwamoto_LeilaneHespporte_M.pdf: 2225260 bytes, checksum: d0f9c4fb0f990871b5301caf7bb6d22b (MD5) Previous issue date: 2014 / Resumo: A espécie Piper umbellatum L., sinonímia Pothomorphe umbellata (L.) Miquel, é conhecida popularmente como pariparoba, caapeba e malvarisco. Tendo em vista as diferentes atividades biológicas comprovadas para a espécie Piper umbellatum e a técnica de microencapsulação por Spray Dryer, o objetivo desse trabalho foi avaliar a atividade farmacológica de extrato bruto padronizado (EBP) de P. umbellatum em modelos de câncer, inflamação, úlcera e verificar se as micropartículas de EBP apresentam atividade antiproliferativa in vitro. O extrato bruto diclorometânico de P. umbellatum possui 23,9% de 4-nerolidilcatecol aproximadamente. Foi avaliado a sua atividade anticâncer em modelo in vivo de tumor sólido de Ehrlich, atividade anti-inflamatória no edema da pata induzido por carragenina e peritonite. EBP foi capaz de reduzir o crescimento do tumor, quando administrado diariamente por via oral, sem sinais de toxicidade. Além disso, diminuiu o edema de pata e a migração de leucócitos no modelo de peritonite dessa forma, acredita-se existir uma relação entre a atividade anticâncer e anti-inflamatória. Também foi comprovada sua a atividade antiulcerogênica e gastroprotetora, relatada pelo uso popular no tratamento de úlceras gástricas. Os mecanismo de ação gastroprotetor envolvido na manutenção dos grupos sulfidrílicos, aumento de glutationa e de muco relacionam sua atividade antiulcerogênica à atividade antioxidante já descrita na literatura. O processo de microencapsulação por Spray Dryer do extrato bruto diclorometânico de P. umbellatum com o amido modificado Purity Gum 1773® permitiu alterar a propriedade graxa inerente a este extrato, insolúvel em água e foi capaz de manter sua atividade antiproliferativa in vitro. Dessa forma, a técnica de Spray Dryer pode ser um caminho para desenvolver um extrato seco de P. umbellatum. Portanto, podemos concluir que P. umbellatum pode ser fonte promissora para o desenvolvimento de novos agentes terapêuticos, tanto para o tratamento de úlceras gástricas quanto para inflamação e câncer / Abstract: The species Piper umbellatum, is popularly known as "pariparoba", "caapeba" and "malvarisco". Despite the different biological activities certified for the species P. umbellatum and the technique of microencapsulation by Spray Dryer, the aim of this study was to evaluate the pharmacological activity of dichloromethane crude extract (DCE) from Piper umbellatum leaves in models of cancer, inflammation and gastric ulcer and also evaluate the antiproliferative activity of microparticles containing standardized crude extract (SDE) in a panel of human tumor cell lines. The SDE from P. umbellatum containing 23,9% of 4-nerolidylcatechol approximately and its in vivo anticancer activity in the Ehrlich solid tumor model as well as its anti-inflammatory activity on carrageenan induced paw edema and peritonitis. The SDE presented in vitro and in vivo antiproliferative activity, being capable to reduce tumor growth when administered daily by oral route, without signals of toxicity. It was also reduced paw edema induced and leukocyte migration on carrageenan induced peritonitis model. Thus establishing a relationship between the anticancer and anti-inflammatory activities.It was also confirmed the popular use of P. umbellatum in the treatment of gastric ulcers, as SDE presented gastroprotective action dependent of the sulfhydryl groups, increase glutatione and mucus pathway and possibly for its antioxidant potential. The microencapsulation process by Spray Dryer of SDE of P. umbellatum with modified starch (Purity Gum 1773®) allowed improvement of the extract solubility, without interfere on its in vitro antiproliferative activity. Thus, the technique of Spray Dryer may be a good alternative to the development of a dry extract of P. umbellatum. Therefore, we conclude that P. umbellatum is a promising source for the development of new therapeutic agents for the treatment gastric ulcers, inflammation and cancer / Mestrado / Farmacologia, Anestesiologia e Terapeutica / Mestra em Odontologia

Background: The aim of this paper was to create an updated Australian guideline on footwear for people with diabetes. Methods: We reviewed new footwear publications, (international guidelines, and consensus expert opinion alongside the 2013 Australian footwear guideline to formulate updated recommendations. Result: We recommend health professionals managing people with diabetes should: (1) Advise people with diabetes to wear footwear that fits, protects and accommodates the shape of their feet. (2) Advise people with diabetes to always wear socks within their footwear, in order to reduce shear and friction. (3) Educate people with diabetes, their relatives and caregivers on the importance of wearing appropriate footwear to prevent foot ulceration. (4) Instruct people with diabetes at intermediate-or high-risk of foot ulceration to obtain footwear from an appropriately trained professional to ensure it fits, protects and accommodates the shape of their feet. (5) Motivate people with diabetes at intermediate-or high-risk of foot ulceration to wear their footwear at all times, both indoors and outdoors. (6) Motivate people with diabetes at intermediate-or high-risk of foot ulceration (or their relatives and caregivers) to check their footwear, each time before wearing, to ensure that there are no foreign objects in, or penetrating, the footwear; and check their feet, each time their footwear is removed, to ensure there are no signs of abnormal pressure, trauma or ulceration. (7) For people with a foot deformity or pre-ulcerative lesion, consider prescribing medical grade footwear, which may include custom-made in-shoe orthoses or insoles. (8) For people with a healed plantar foot ulcer, prescribe medical grade footwear with custom-made in-shoe orthoses or insoles with a demonstrated plantar pressure relieving effect at high-risk areas. (9) Review prescribed footwear every three months to ensure it still fits adequately, protects, and supports the foot. (10) For people with a plantar diabetic foot ulcer, footwear is not specifically recommended for treatment; prescribe appropriate offloading devices to heal these ulcers. Conclusions: This guideline contains 10 key recommendations to guide health professionals in selecting the most appropriate footwear to meet the specific foot risk needs of an individual with diabetes.

Neuropathy is one of the main long term complications of diabetes affecting 30-50% of patients. It is the major contributing factor for foot ulceration with a life time risk which may be as high as 25%. Hence neuropathy leads to reduced pain and pressure perception, anatomic deformities and an impaired microcirculation. More specifically, unperceived minor trauma results in cutaneous injury which when combined with an inadequate pressure induced vasodilator response leads to tissue breakdown and ulceration. Once ulcers form, healing may be delayed or difficult to achieve, particularly if infection occurs in the deeper tissues and bone which can then lead to amputation. In the UK, South Asians (people originating from India, Pakistan and Bangladesh) have an excess mortality for coronary artery disease (CAD), stroke and end-stage renal disease when compared to white Europeans. However, it has been shown that South Asian people with type 2 diabetes in the UK are only one third as likely to have a foot ulcer compared with White European diabetic patients. This has been attributed to lower levels of peripheral neuropathy in Asians, but has not been systematically explored in detail. In the present study, both neurological and vascular deficits in a group of South Asian and European patients with type II diabetes have been assessed. The results demonstrate that: • South Asian diabetic patients have poorer glycaemic control, but paradoxically lower triglycerides. This finding may be relevant to the finding that they have a lower incidence of neuropathy, as triglycerides have been related to neuropathy and foot ulceration. • South Asians compared to Europeans have better small fibre function and a trend for better structure (Intra epidermal nerve fibre density and corneal nerve morphology) and large fibre function assessed with nerve conduction studies. • South Asians have higher foot skin oxygenation and hyperaemic blood flow response to heating. • South Asians have a thicker epidermis and a trend for a better capillary density. Therefore these alterations may protect South Asians from the development of foot ulceration.

Pressure injuries (pressure ulcers, bed sores) are a localized injury to skin and/or underlying tissues as a result of excessive pressure with or without shear force or friction. These injuries are painful, increase risk of secondary infection, have prolonged healing times (months), and cost the U.S. healthcare system 26.8 billion dollars annually. While these injuries are considered preventable, pressure injuries have an overall prevalence of 12.3% in U.S. healthcare facilities with 40% of all pressure injury incidents being facility acquired. The current clinical standard of rotating patients every two hours to offload tissues and performing visual skin assessments is not sufficient for preventing all pressure injuries. The susceptibility to pressure injury formation varies between individuals, and visual skin assessments cannot detect tissue damage below the skin surface. Objective and non-invasive methods for detecting early signs of tissue damage, such as ultrasound and subepidermal moisture scanners, have shown promise in detecting subcutaneous damage. However, these spot scan techniques require trained personnel for interpretation and can lag the pressure loading event by more than 2 days. As part of an ongoing effort to develop an objective and wearable noninvasive monitor to detect early changes related to pressure injury formation, a low-cost, battery-powered bioimpedance sensor was developed and tested on ex vivo and in vivo animal models. The developed sensor is capable of measuring typical human skin impedances with errors of less than 6% as determined using a human skin equivalent electrical model. Continuous bioimpedance-based monitors need to be capable of measuring accurately during changing skin conditions, such as changes in temperature and sweating. The effect of changes in skin microclimate on bioimpedance measurements was investigated using an ex vivo porcine dermis model. We found that increased tissue hydration, simulated by washing porcine dermis in saline, can significantly impact impedance magnitude and phase angle measurements. Finally, an in vivo pressure ulcer rat model was used to determine the relationship between bioimpedance measures, tissue loading intensities, and clinical ulcer staging. Changes between bioimpedance measures before and immediately following the pressure loading event had moderate (0.55) to strong (0.8) linear and rank order correlation with tissue loading intensity (pressure x time). Thresholds were determined to separate clinical ulcer stages via bioimpedance measures taken 3 days prior to visual skin assessment and found that the majority of ulcers could be properly categorized into ulcer/no ulcer groups. These results indicate that bioimpedance is a promising parameter in the development of a continuous noninvasive system for early pressure ulcer detection.

Pressure injuries (pressure ulcers, bed sores) are a localized injury to skin and/or underlying tissues as a result of excessive pressure with or without shear force or friction. These injuries are painful, increase risk of secondary infection, have prolonged healing times (months), and cost the U.S. healthcare system 26.8 billion dollars annually. While these injuries are considered preventable, pressure injuries have an overall prevalence of 12.3% in U.S. healthcare facilities with 40% of all pressure injury incidents being facility acquired. The current clinical standard of rotating patients every two hours to offload tissues and performing visual skin assessments is not sufficient for preventing all pressure injuries. The susceptibility to pressure injury formation varies between individuals, and visual skin assessments cannot detect tissue damage below the skin surface. Objective and non-invasive methods for detecting early signs of tissue damage, such as ultrasound and subepidermal moisture scanners, have shown promise in detecting subcutaneous damage. However, these spot scan techniques require trained personnel for interpretation and can lag the pressure loading event by more than 2 days. As part of an ongoing effort to develop an objective and wearable noninvasive monitor to detect early changes related to pressure injury formation, a low-cost, battery-powered bioimpedance sensor was developed and tested on ex vivo and in vivo animal models. The developed sensor is capable of measuring typical human skin impedances with errors of less than 6% as determined using a human skin equivalent electrical model. Continuous bioimpedance-based monitors need to be capable of measuring accurately during changing skin conditions, such as changes in temperature and sweating. The effect of changes in skin microclimate on bioimpedance measurements was investigated using an ex vivo porcine dermis model. We found that increased tissue hydration, simulated by washing porcine dermis in saline, can significantly impact impedance magnitude and phase angle measurements. Finally, an in vivo pressure ulcer rat model was used to determine the relationship between bioimpedance measures, tissue loading intensities, and clinical ulcer staging. Changes between bioimpedance measures before and immediately following the pressure loading event had moderate (0.55) to strong (0.8) linear and rank order correlation with tissue loading intensity (pressure x time). Thresholds were determined to separate clinical ulcer stages via bioimpedance measures taken 3 days prior to visual skin assessment and found that the majority of ulcers could be properly categorized into ulcer/no ulcer groups. These results indicate that bioimpedance is a promising parameter in the development of a continuous noninvasive system for early pressure ulcer detection.

Although pressure ulcer (PrU) development is now generally considered an indicator for quality of care, questions and concerns about situations in which they are unavoidable remain. Considering the importance of this issue and the lack of available research data, in 2010 the National Pressure Ulcer Advisory Panel (NPUAP) hosted a multidisciplinary conference to establish consensus on whether there are individuals in whom pressure ulcer development may be unavoidable and whether a difference exists between end-of-life skin changes and pressure ulcers. Thirty-four stakeholder organizations from various disciplines were identified and invited to send a voting representative. Of those, 24 accepted the invitation. Before the conference, existing literature was identified and shared via a webinar. A NPUAP task force developed standardized consensus questions for items with none or limited evidence and an interactive protocol was used to develop consensus among conference delegates and attendees. Consensus was established to be 80% agreement among conference delegates. Unanimous consensus was achieved for the following statements: most PrUs are avoidable; not all PrUs are avoidable; there are situations that render PrU development unavoidable, including hemodynamic instability that is worsened with physical movement and inability to maintain nutrition and hydration status and the presence of an advanced directive prohibiting artificial nutrition/hydration; pressure redistribution surfaces cannot replace turning and repositioning; and if enough pressure was removed from the external body the skin cannot always survive. Consensus was not obtained on the practicality or standard of turning patients every 2 hours nor on concerns surrounding the use of medical devices vis-à-vis their potential to cause skin damage. Research is needed to examine these issues, refine preventive practices in challenging situations, and identify the limits of prevention.

Pressure ulcer prevalence and incidence data are increasingly being used as indicators of quality of care and the efficacy of pressure ulcer prevention protocols. In some health care systems, the occurrence of pressure ulcers is also being linked to reimbursement. The wider use of these epidemiological analyses necessitates that all those involved in pressure ulcer care and prevention have a clear understanding of the definitions and implications of prevalence and incidence rates. In addition, an appreciation of the potential difficulties in conducting prevalence and incidence studies and the possible explanations for differences between studies are important. An international group of experts has worked to produce a consensus document that aims to delineate and discuss the important issues involved, and to provide guidance on approaches to conducting and interpreting pressure ulcer prevalence and incidence studies. The group's main findings are summarised in this paper.

The thesis investigates the role of psycotherapy in treating peptic ulcers, offering a new approach, "Re-evaluation Co-counseling," a peer cathartic therapy.