Cancer therapy represents a challenge, even with the current scientific developments. Over the years, several studies have shown that the application of antitumor drug nanocarriers is an efficient strategy; however, it requires further improvement. Several nanosystems have been developed, some of which are already in use, including liposomes. Polymer-based nanocarriers are still being adjusted to the peculiarities of the human body due to the biological barriers that were encountered by the first systems that were developed. Among them, the formation of corona proteins, clearance by the endothelial reticulum system and kidneys, activation of the immune system, lack of selectivity, and difficult release have been extensively studied and improved with the development of new devices. In this review, we explore the evolution of primary nanocarriers based on polymeric micelles and highlight the gaps that remain in this field to assist in the research of new systems with superior therapeutic indices. challenge developments years strategy however improvement developed use liposomes Polymerbased Polymer them proteins kidneys selectivity devices review indices

ABSTRACT Introduction Several techniques of robotic-assisted radical prostatectomy (RARP) using the da Vinci SP (SP) have been described since its clearance by the FDA (Food and Drug Administration) in 2018 ( 1 , 2 ). Even with the expanding literature about this robot, the SP technology has been restricted to a few centers in the US and Asia due to the recent release of this robot in the marked.3 In this scenario, we provided, in this video compilation, a consensus of SP referral centers describing the current approaches and techniques of da Vinci SP Radical prostatectomy (SP-RARP). Surgical Technique We have illustrated five different techniques, including transperitoneal, extraperitoneal, Retzius-sparing, transvesical, and transperineal ( 4 - 6 ). Each surgery demonstrated crucial steps from the trocar placement until anastomosis. All approaches follow anatomic concepts and landmarks to minimize positive surgical margins, optimize oncological outcomes and promote optimal functional recovery. The trocar placement and the use of an assistant port were selected according to the operative technique of each institution. None of these surgeries had intra- or postoperative complications, and the pain management until discharge was controlled without using narcotics. All patients were discharged in less than 16 hours of surgery. Conclusion Robotic-assisted radical prostatectomy performed with the da Vinci SP is feasible and safe with optimal perioperative outcomes. Five different approaches were described in this video compilation, and we believe that the technical details provided by this multicentric collaboration are crucial for centers willing to initiate the SP approach to radical prostatectomy.

ABSTRACT Introduction/framework/objectives Pneumoconiosis are the most frequent occupational diseases. Silicosis is caused by inhaling breathable crystalline Silica. It is a diffuse interstitial fibronodular lung disease. Initially it is asymptomatic, however, it is usually progressive and without cure. The diagnosis is partially based on a history of professional exposure. It is more prevalent in countries with considerable unemployment and/or little or no Health and Safety Surveillance at Work. Methodology This is a Bibliographic Review, initiated through a search carried out in January 2022, in the databases “CINALH plus with full text, Medline with full text, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, Nursing and Allied Health Collection: comprehensive, MedicLatina and RCAAP”. Contents Silica or silicon dioxide (SiO2) is made up of oxygen and silicon. In nature it exists in amorphous and crystalline forms. The International Agency for Research on Cancer (IARC) considered inhaled crystalline Silica as a human carcinogen (group 1), probably due to cellular damage, inflammation, oxidative stress and inhibition of clearance. Amorphous silica is not considered carcinogenic to humans (group 3). Silicosis exists in all countries, but is more prevalent in the ones less developed, even realizing that the real incidence should be higher than the official one, due to the situation being underreported. In more developed countries, the incidence/prevalence has decreased, due to the improvement of working conditions. Exposure is relevant via inhalation; cutaneous and digestive tracts generally do not have important consequences in the work context. The health risk varies with concentration, particle size- diameter, surface and shape (more dangerous if smaller), exposure time, type of silica (crystalline, tridymite and cristobalite are the most harmful, although more rare), density, water and lipid solubility, chemical reactivity, hygroscopic and electrostatic character, temperature, air speed and employee physical activity. Also important are gender, body area, age, general health status, previous pathologies and smoking- that is, individual susceptibility. The particles can be inhaled, thoracic or respirable (the latter are able to settle in the lungs). The shape, size and density of dust will affect the behavior and penetration into the respiratory system. The respirable fraction consists of particles smaller than 10 micrometers, that is, they can reach the area where gas exchange takes place; larger than that, they are usually deposited in the nasal and thoracic region. Silica nanoparticles smaller than 100 nanometers can reach the bloodstream. After inhalation, Silica particles are mainly deposited in the bronchioles and alveoli; if mucociliary clearance is not sufficient, inflammation (alveolitis) develops, which can lead to fibrosis and cancer. Macrophage activation generates free radicals/reactive oxygen species, which are not always attenuated by anti-oxidant defenses. Continued exposure enhances the release of cytokines which, in turn, activate more macrophages, neutrophils and lymphocytes; the increased production of collagen will then lead to said fibrosis, decreasing lung profitability and efficiency; that is, decreasing gas exchange; being that it can also reach the pleura. Discussion and Conclusions Despite the advances provided by an increasingly effective Health and Safety system, Silicosis is still a problem in some contexts, so it is necessary that the professionals working in these teams have reasonable knowledge regarding the sectors/tasks where it can occur, auxiliary diagnostic tests and other surveillance parameters, collective and individual protection measures, as well as possible implications for the classification of aptitude to work. It would be relevant to better understand the national scenario, through the dissemination of investigations carried out in this context.

RESUMO Introdução/enquadramento/objetivos As pneumoconioses são as doenças profissionais mais frequentes. A Silicose é causada pela inalação de Sílica cristalina respirável. Trata-se de uma patologia pulmonar fibronodular intersticial difusa. Inicialmente ela é assintomática, contudo, geralmente progressiva e sem cura. O diagnóstico fundamenta-se parcialmente na história profissional de exposição. É mais prevalente em países com uma taxa de desemprego considerável e/ou pouca ou nenhuma vigilância da Saúde e Segurança no trabalho. Metodologia Trata-se de uma Revisão Bibliográfica, iniciada através de uma pesquisa realizada em janeiro de 2022, nas bases de dados “CINALH plus with full text, Medline with full text, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Cochrane Methodology Register, Nursing and Allied Health Collection: comprehensive, MedicLatina e RCAAP”. Conteúdo A Sílica ou o dióxido de silício (SiO2) é constituída por oxigénio e silício. Na natureza existe nas formas amorfa e cristalina. A International Agency for Research on Cancer (IARC) considerou a Sílica cristalina inalada como cancerígena para humanos (grupo 1), provavelmente devido ao dado celular, inflamação, stress oxidativo e inibição da clearence. A Sílica amorfa não é considerada cancerígena para humanos (grupo 3). A Silicose existe em todos os países, mas é mais prevalente nos menos desenvolvidos, mesmo percebendo-se que a incidência real deverá ser superior à oficial, devido à situação estar sub-reportada. Nos países mais desenvolvidos a incidência/prevalência tem diminuído, devido à melhoria das condições de trabalho. A exposição é relevante via inalatória; vias cutânea e digestiva não têm geralmente consequências importantes em contexto laboral. O risco para a saúde varia com a concentração, dimensão das partículas- diâmetro, superfície e forma (mais perigosas se mais pequenas), tempo de exposição, tipo de Sílica (a cristalina, tridimita e a cristobalita são as mais lesivas, ainda que mais raras), densidade, solubilidade em água e lípidos, reatividade química, carater higroscópico e eletrostático, temperatura, velocidade do ar e atividade física do funcionário. Por sua vez, neste último, destacam-se o género, área corporal, idade, estado geral de Saúde, patologias prévias e tabagismo; ou seja, a suscetibilidade individual. As partículas podem ser inaláveis, torácicas ou respiráveis (estas últimas conseguem se depositar nos pulmões). A forma, tamanho e densidade das poeiras irão condicionar o comportamento e penetração no aparelho respiratório. A fração respirável é constituída por partículas com menos de 10 micrómetros, ou seja, com capacidade para atingir a zona onde se efetua a troca gasosa; maiores que isso, geralmente ficam depositadas na região nasal e torácica. As nanopartículas com Sílica menores que 100 nanómetros podem chegar à circulação sanguínea. Após a inalação, as partículas de Sílica depositam-se sobretudo nos bronquíolos e alvéolos; se a clearence mucociliar não for suficiente, surge inflamação (alveolite), que poderá posteriormente levar a fibrose e cancro. A ativação dos macrófagos origina radicais livres/espécies reativas de oxigénio, que nem sempre são atenuados pelas defesas anti-oxidantes. A exposição continuada potencia a libertação de citoquinas que, por sua vez, ativam mais macrófagos, neutrófilos e linfócitos; a produção aumentada de colagénio levará então à dita fibrose, diminuindo a rentabilidade e eficácia pulmonares; ou seja, diminuindo as trocas gasosas; sendo que esta pode também atingir a pleura. Discussão e Conclusões Apesar dos avanços proporcionados por um sistema de Saúde e Segurança cada vez mais eficaz, ainda assim a Silicose constitui um problema em alguns contextos, pelo que é necessário que os profissionais a exercer nestas equipas tenham conhecimentos razoáveis relativos aos setores/tarefas onde esta pode ocorrer, exames auxiliares de diagnóstico e restantes parâmetros da vigilância, medidas de proteção coletivas e individuais, bem como eventuais implicações para a classificação de aptidão. Seria relevante conhecer melhor o panorama nacional, através da divulgação de investigações efetuadas neste contexto.

RESUMO Objetivo caracterizar o tempo de decanulação e liberação de dieta por via oral dos pacientes submetidos à cirurgia do câncer de boca no Hospital Alberto Cavalcante, e verificar quais fatores estão associados ao atraso no tempo de decanulação e de liberação de dieta por via oral. Método estudo observacional de análise do banco de dados de 33 pacientes adultos tratados cirurgicamente do câncer de boca e atendidos no período de 2012 a 2017. As variáveis sociodemográficas (idade e sexo) e clínicas (tipo de cirurgia, extensão operatória, tipo de reconstrução, condições clínicas e tempos de decanulação e reintrodução da via oral) foram coletadas por meio de análise de prontuários eletrônicos. Foi realizada análise estatística descritiva com medidas de tendência central, dispersão e proporções. Para análise de associação foi utilizado o teste não paramétrico Mann-Whitney para amostras independentes. Resultados Dos 33 participantes, predominou o sexo masculino e idosos, 69,8% realizaram ressecção de mais de uma estrutura. A mediana do tempo de decanulação entre os pacientes com câncer de boca foi de 8 dias, e da liberação da via oral foi de 9,5 dias. As ressecções com mais de uma estrutura, a presença de fístula e de deiscência interferiram no tempo de liberação de via oral. Conclusão a mediana de tempo de decanulação foi de oito dias e de liberação de via oral de 9,5 dias. As ressecções com mais de uma estrutura, a presença de fístula, e de deiscência de sutura, estão associadas com o aumento do tempo de liberação de via oral.

ABSTRACT Purpose to analyze the time of decannulation and oral diet release of patients undergoing oral cancer surgery at the Hospital Alberto Cavalcante and to verify which factors are associated with the time of decannulation and oral diet release. Methods an observational study of the database of 33 adult patients surgically treated with oral cancer and served between 2012 and 2017. The socio-demographic variables (age and gender) and clinical variables (type of surgery, surgical extension, type of reconstruction, clinical conditions and times of decannulation and reintroduction of the oral route) were collected through electronic medical records analysis. Descriptive statistical analysis was performed with measures of central tendency, dispersion and proportions. For the association analysis, the non-parametric Mann-Whitney U test was used for independent samples. Results of the 33 participants, male and elderly predominated, 69.8% underwent resection of more than one structure. The median time of decannulation among patients with oral cancer was 8 days, and oral clearance of 9.5 days. Resections with more than one structure, the presence of fistula and dehiscence interfered in the oral release time. Conclusion the median time of decannulation was eight days and oral release time of 9.5 days. Resections with more than one structure, the presence of fistula, and suture dehiscence are associated with increased oral release time.

ABSTRACT Introduction: Currently, the management of treatments in cystic fibrosis (CF) is mainly focused to control symptoms, which consist of mucus retention and chronic infection. The pulmonary route is proposed as an interesting alternative for administering drugs, especially antimicrobials. However, the rapid clearance of these, which leads to low drug levels and increased dosage regimens, as well as the appearance of adverse effects, make nanotechnology an interesting strategy for this disease. Objective: to study and analyze the different nanoparticulate systems available for use via the lung, specifying the use of lipid systems for the treatment of CF. Method: a non-systematic search of articles in different databases was carried out, mainly in the last 10 years, following established guidelines for selecting keywords. Results: The progress in recent years makes CF become an adult disease. Current treatments are increasingly being displaced by other alternatives, such as nanoparticular systems, being suitable for pulmonary administration due to their small size, sustained release and high biocompatibility. Among these, liposomes stand out for their structural similarity to lung surfactant, as well as for their ability to destroy bacterial biofilms. Most of the formulations contained a single drug. Conclusion: Scientific literature evidenced that research studies should be directed towards the development of formulations that are intended to destroy the biofilm.

RESUMEN Introducción: Actualmente, los tratamientos existentes para tratar la fibrosis quística (FQ) están diseñados para controlar sus síntomas, consistentes principalmente en retención de moco e infección crónica. Se propone la vía pulmonar como alternativa para la administración de los fármacos, principalmente antimicrobianos. Sin embargo, su rápido aclaramiento, que conduce a niveles bajos de fármaco e incremento de los regímenes posológicos, así como la aparición de efectos adversos, hacen de la nanotecnología una estrategia interesante para esta enfermedad. Objetivo: estudiar y analizar los diferentes sistemas nanoparticulares existentes para su uso por vía pulmonar, concretando en el uso de sistemas lipídicos para el tratamiento de la FQ. Método: se realizó una búsqueda no sistemática de artículos en diferentes bases de datos, en los últimos 10 años principalmente, siguiendo pautas establecidas de palabras clave. Resultados: Los progresos que se han conseguido en los últimos años hacen que la FQ pase a ser una enfermedad de adultos. Los tratamientos que se están usando en la actualidad están siendo cada vez más desplazados por otras alternativas, como los sistemas nanoparticulares, siendo idóneos para la administración pulmonar debido a su pequeño tamaño, su liberación sostenida y su elevada biocompatibilidad. Entre éstos, destacan los liposomas por su similitud estructural con el surfactante pulmonar, así como por su capacidad de destruir las biopelículas bacterianas. La mayoría de las formulaciones encontradas contenían un solo fármaco. Conclusión: Existen evidencias científicas que indican que la investigación debe dirigirse hacia el desarrollo de formulaciones que sean capaces de destruir la biopelícula.

BACKGROUND: Tracheostomal stenosis is a distressing complication with a high incidence rate post laryngectomy. We aimed to assess the deltopectoral flap (DPF) for tracheostomal stenosis correction in irradiated patientsMETHODS: Six patients with tracheostomal stenosis, 3 of whom developed restenosis after prior use of local flaps, were managed using a DPF to reconstruct the defect following a vertical incision release of the stenotic band down to the inferior tracheal cartilaginous ring. Healing absence of restenosis, alleviation of the symptoms of difficulty in breathing and clearance of secretions were considered a successful composite endpointRESULTS: Over a median follow-up period of 11 months all patients maintained patency, and symptoms of difficulty in breathing and clearing of secretions were alleviatedCONCLUSION: The deltopectoral flap is a rapid, reliable flap for the management of tracheostomal stenosis in irradiated patients. It brings well-vascularised tissue into the site of reconstruction and, in the short term, stomal patency and symptom relief were achieved

Introdução. A obesidade, um importante fator de risco para o desenvolvimento da insuficiência cardíaca (IC), é um fator prognóstico protetor. Esse possível paradoxo pode explicar-se pelo papel protetor do tecido adiposo marrom (BAT), das adipocinas anti-inflamatórias e pela conexão do tecido adiposo ao coração mediada pelos peptídeos natriuréticos (NPs). Material e métodos. As evidências sobre os três mecanismos citados são discutidas. Resultados. Em animais e em humanos, tanto obesos como em portadores de IC, há aumento do BAT mas, é menos ativo, com menor expressão de proteína desacopladora tipo 1 (UCP1), limitando seu potencial protetor. A atividade anti-inflamatória de algumas adipocinas está associada à promoção da regeneração do miocárdio, formação de novos vasos sanguíneos, redução da pós-carga, melhora dos processos metabólicos em cardiomiócitos. Recentemente demonstrou-se que NPs, além de seu papel na homeostase circulatória, têm um papel na regulação do consumo energético e na regulação do tecido adiposo, interferindo na liberação de adipocinas. Sabe-se que os NPs estão diminuídos nos obesos, por haver maior clearence ou menor secreção. Conclusão. O papel das adipocinas anti-inflamatórias e a conexão do tecido adiposo ao coração mediada pelos NPs são mecanismos promissores para explicar o paradoxo da obesidade na IC. Localizamos somente dois estudos sobre o papel anti-inflamatório das adipocinas, com evidências diretas. Apesar da existência de inúmeros estudos sobre os NPs, as evidências são menos consistentes. Trata-se de uma área que merece ser acompanhada na tentativa de compreender o paradoxo da obesidade na IC, o que poderia permitir uma melhor abordagem ao paciente acometido por essa síndrome.

Introduction. Obesity, an important risk factor for the development of heart failure (HF), is a protective prognostic factor. This paradox can be explained by the protective role of brown adipose tissue (BAT), anti-inflammatory adipokines and the crosstalk between adipose tissue and heart mediated by natriuretic peptides (NPs). Material and methods. Evidence for these three mechanisms is discussed. Results. In animals and humans models, in both, obese and patients with HF, there is an increase in BAT, but it is less active, with lower expression of uncoupling protein type 1 (UCP1), limiting its protective potential. The antiinflammatory effect of some adipokines is associated with myocardial regeneration, production of new blood vessels, reduction of afterload and potentiation of metabolic processes in cardiomyocytes. It has been shown that NPs, in addition to their role in circulatory homeostasis, play a role in the energy tightening and regulation of adipose tissue, interfering with the release of adipokines. It is known that NPs are decreased in obese, due to a greater clearance or lower secretion. Conclusion. The role of anti-inflammatory adipokines and the crosstalk between adipose tissue and heart mediated by NPs are promising mechanisms to explain the paradox of obesity in HF. We found only two studies on the antiinflammatory role of adipokines, with direct evidence. Despite the existence of numerous studies on NPs, the evidence is less consistent. This area deserves to be followed in an attempt to understand the paradox of obesity in HF, which could allow a better care to the patient affected.

Background:Visceral leishmaniasis (VL) or Kala-Azar (KA) is one of the most deadly forms of disease among all neglected tropical diseases. There are no satisfactory drugs or vaccine candidates available for this dreaded disease. Our previous studies showed promising therapeutic and prophylactic efficacy of the live, radio-attenuated parasites through intramuscular (I.M.) and intraperitoneal (I.P.) route in BALB/c mice model.Methods:The T-cell proliferation level, the mRNA expression level of inducible nitric oxide synthase (iNOS) and tumor growth factor-beta (TGF-β) genes and finally the phosphorylation levels of phosphoinositide dependent kinase 1 (PDK1), phosphoinositide 3 kinase (PI3K) and p38 mitogen activated protein kinase (p38MAPK) molecules were checked in BALB/c mice model immunized with radio-attenuated Leishmania donovaniparasites through I.M. route.Results:Higher T-cell proliferation, increased iNOS level, and suppressed TGF-β level were found in treated infected animal groups (100 and 150 Gy) in relation to untreated infected animals. Likewise, phosphorylation levels of PDK1, PI3K and p38MAPK of these two groups were increased when compared to untreated infected controls.Conclusion:The clearance of the parasites from treated infected groups of animals may be mediated by the restoration of T-cell due to therapy with radio-attenuated L. donovaniparasites. The killing of parasites was mediated by increase in nitric oxide release through PDK1, PI3K and p38MAPK signaling pathways. A lower TGF-β expression has augmented the restored Th1 ambience in the 100 and 150 Gy treated animal groups proving further the efficacy of the candidate vaccine.

The neural retina is a highly complex tissue composed of excitatory and inhibitory neurons and glial cells. Glutamate, the main excitatory neurotransmitter, mediates information transfer from photoreceptors, bipolar cells, and ganglion cells, whereas interneurons, mainly amacrine and horizontal cells, use γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter. In this review we place an emphasis on glutamate and GABA transporters as highly regulated molecules that play fundamental roles in neurotransmitter clearance, neurotransmitter release, and oxidative stress. We pharmacologically characterized glutamate transporters in chicken retina cells and identified two glutamate transporters: one Na+-dependent transporter and one Na+-independent transporter. The Na+-dependent uptake system presented characteristics related to the high-affinity xAG- system (EAAT1), and the Na+-independent uptake system presented characteristics related to the xCG- system, which highly contributes to glutamate transport in the retina. Glutamate shares the xCG- system with another amino acid, L-cysteine, suggesting the possible involvement of glutathione. Both transporter proteins are present mainly in Müller glial cells. GABA transporters (GATs) mediate high-affinity GABA uptake from the extracellular space and terminate the synaptic action of GABA in the central nervous system. GABA transporters can be modulated by molecules that act on specific sites to promote transporter phosphorylation and dephosphorylation. In addition to a role in the clearance of GABA, GATs may also release GABA through a reverse transport mechanism. In the chicken retina, a GAT-1 blocker, but not GAT2/3 blocker, was shown to inhibit GABA uptake, suggesting that GABA release from retina cells is mainly mediated by a GAT-1-like transporter.

The host immune response plays an important role in viral clearance in patients who are chronically infected with hepatitis C virus (HCV) and are treated with interferon and ribavirin. Activation of the immune system involves the release of pro and anti-inflammatory molecules that can be measured in plasma samples. The present study aimed to evaluate the association between pretreatment plasma levels of chemokines and soluble tumor necrosis factor receptors (sTNF-R) and the virological response in treated patients with chronic hepatitis C infection. Forty-one chronically-infected HCV patients that were being treated with interferon-α (IFN-α) plus ribavirin were included in the study. Socio-demographic, clinical and laboratory data were collected and pretreatment plasma levels of chemokine CCL2, CCL3, CCL11, CCL24, chemokine CXCL9, CXCL10, sTNF-R1 and sTNF-R2 were measured. The virological response was assessed at treatment week 12, at the end of treatment and 24 weeks after treatment. Pretreatment CXCL10 levels were significantly higher in patients without an early virological response (EVR) or sustained virological response (SVR) compared to responders [512.9 pg/mL vs. 179.1 pg/mL (p = 0.011) and 289.9 pg/mL vs. 142.7 pg/mL (p = 0.045), respectively]. The accuracy of CXCL10 as a predictor of the absence of EVR and SVR was 0.79 [confidence interval (CI) 95%: 0.59-0.99] and 0.69 (CI 95%: 0.51-0.87), respectively. Pretreatment plasma levels of the other soluble inflammatory markers evaluated were not associated with a treatment response. Pretreatment CXCL10 levels were predictive of both EVR and SVR to IFN-α and ribavirin and may be useful in the evaluation of candidates for therapy.

O tratamento de doenças do segmento posterior do olho é limitado pela dificuldade no transporte de doses efetivas de fármacos para o vítreo, retina e coróide. Os fármacos aplicados topicamente são pouco absorvidos por causa da baixa permeabilidade dos tecidos oculares externos e ao lacrimejamento. Embora a administração sistêmica seja capaz de transportar fármacos para o segmento posterior do olho, as barreiras hemato-aquosa e hematorretiniana dificultam a absorção e, normalmente, são necessárias doses elevadas, as quais estão geralmente associadas a potenciais efeitos adversos. Injeções intravitreais são capazes de transportar fármacos para o segmento posterior do olho, mas é uma técnica invasiva, pouco tolerada pelos pacientes e apresenta riscos de infecções oculares e danos aos tecidos. Visando a obtenção de níveis terapêuticos adequados de fármacos no segmento posterior do bulbo do olho por longos períodos, sistemas de liberação poliméricos implantados diretamente no vítreo estão sendo investigados para o tratamento de várias doenças vítreo-retinianas. Esses implantes podem ser preparados a partir de diferentes polímeros biocompatíveis, biodegradáveis ou não-biodegradáveis. Nesta revisão, as principais características destes implantes transportadores de fármacos são descritas, expondo suas potencialidades de aplicação clínica.

The treatment of diseases affecting the posterior segment of the eye is limited by the difficulty in transporting effective doses of drugs to the vitreous, retina, and choroid. Topically applied drugs are poorly absorbed due to the low permeability of the external ocular tissues and tearing. The blood-retina barrier limits drug diffusion from the systemic blood to the posterior segment, thus high doses of drug are needed to maintain therapeutic levels. In addition, systemic side effects are common. Intraocular injections could be an alternative, but the fast flowing blood supply in this region, associated with rapid clearance rates, causes drug concentration to quickly fall below therapeutic levels. To obtain therapeutic levels over longer time periods, polymeric sustained-drug release systems implanted within the vitreous are being studied for the treatment of vitreoretinal disorders. These systems are prepared using different kinds of biodegradable or non-biodegradable polymers. This review aims to demonstrate the main characteristics of these drug delivery implants and their potential for clinical application.

Objective: the alteration of hormones regulating sodium and water status is related to renal failure in obstructive jaundice (OJ). Experimental design: OJ was induced by common bile duct ligation. Samples were obtained from the control (SO) and OJ groups at 24 and 72 hours, and at 7 days. Different parameters related to biliary obstruction, liver and renal injury, and vasoactive mediators such as renin, aldosterone, endothelin-1 (ET-1) and prostaglandin E2 (PGE2) were studied. Results: bile duct ligation caused an increase in total bilirubin (p < 0.001) and alkaline phosphatase (AP) (p < 0.001). The SO and OJ groups had the same values for diuresis, renin, and creatinine clearance at 24 h. However, animals with OJ had a lower sodium concentration in urine than SO animals (p < 0.01), as well as an increase in aldosterone levels (p < 0.03). ANP levels were moderately increased during OJ but did not reach statistical significance when compared to the SO group. In contrast, OJ animals showed a rise in serum ET-1 concentration (p < 0.001) and increased PGE2 in urine (p < 0.001). Conclusions: biliary obstruction induced an increase in ET-1 release and PGE2 urine excretion. These hormones might play a role during the renal complications associated with renal disturbances that occur during OJ.

Cytokines make up a network of molecules involved in the regulation of immune response and organ functional homeostasis. Cytokines coordinate both physiological and pathological processes occurring in the liver during viral infection, including infection control, inflammation, regeneration, and fibrosis. Hepatitis B and hepatitis C viruses interfere with the complex cytokine network brought about by the immune system and liver cells in order to prevent an effective immune response, capable of viral control. This situation leads to intrahepatic sequestration of nonspecific inflammatory infiltrates that release proinflammatory cytokines, which in turn favor chronic inflammation and fibrosis. The therapeutical administration of cytokines such as interferon alpha may result in viral clearance during persistent infection, and revert this process.

Diminazene remains one of South Africa's most commonly used antiprotozoal agents for the management of babesiosis in dogs . Although the drug has been on the market for over 40 years, its intravenous pharmacokinetics are poorly known. To better understand the pharmacokinetics of the drug Berenil®, it was reconstituted in sterile water and administered intravenously to 6 adult German shepherd dogs. All 6 dogs demonstrated the previously described secondary peak in the plasma concentration versus time profile. The plasma pharmacokinetics for diminazene are described by both non-compartmental and compartmental models. From non-compartmental analysis, the area under curve to the last sample point (AUQast), clearance (CL) and volume of distribution (Vz) were 4.65 ± 1.95 ng/ml/h, 0.77 ± 0.18 l/kg/h and2.28 ± 0.60 l/kg respectively. For compartmental modelling, the plasma concentrations were fitted to both a 2-compartmental open model and a recirculatory enterohepatic model. From the recirculation model, the rate of release and re-entry into the central compartment varied markedly with the rate of release from the gall bladder (Ttom) being estimated at 27 ± 20.90 h. Once released, drug re-entry into the central compartment was variable at 9.70 ± 5.48 h. With normal biliary excretion time being about 2 h, this indicates that the redistribution cannot be occurring physiologically from the bile. Although it was not possible to identify the site from which sequestration and delayed release is occurring, it is believed that it is most likely from the liver. The study therefore showed that the secondary peak described for the pharmacokinetics of intramuscular administered diminazene in the dog is not related to biphasic absorption.

Iron is essential for many aspects of cellular function. However, it also can generate oxygen-based free radicals that result in injury to biological molecules. For this reason, iron acquisition and distribution are tightly regulated. Constant exposure to the atmosphere results in significant exposure of the lungs to catalytically active iron. The lungs have a mechanism for detoxification to prevent associated generation of oxidative stress. Those same proteins that participate in iron uptake in the gut are also employed in the lung to transport iron intracellularly and sequester it in an inactive form within ferritin. The release of metal is expedited (as transferrin and ferritin) from lung tissue to the respiratory lining fluid for clearance by the mucocilliary pathway or to the reticuloendothelial system for long-term storage. This pathway is likely to be the major method for the control of oxidative stress presented to the respiratory tract.