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INTRODUÇÃO E/OU FUNDAMENTO: Em 1945 Martorell descreveu uma série de casos de úlceras supramaleolares dolorosas secundárias a arteriolosclerose subcutânea em hipertensos mal controlados. Estas úlceras hipertensivas (UH) acometem predominantemente a região laterodorsal do tornozelo, na ausência de doença arterial oclusiva periférica (DAOP), insuficiência venosa crônica ou outras vasculites. Afetam mais comumente mulheres entre 50 e 60 anos, são intensamente dolorosas e estão associadas a hipertensão arterial (HA) mal controlada. MÉTODOS: Relatamos o caso de um paciente de sexo masculino, 56 anos, negro, portador de obesidade grau 2 (peso 115 kg; IMC 37), acompanhado por HA primária refratária, que evoluiu com úlcera maleolar laterodorsal direita crônica e intensamente dolorosa. Apesar da prescrição de 7 classes de anti-hipertensivos (olmesartana, clortalidona, anlodipino, espironolactona, atenolol, hidralazina e clonidina), retornou com Monitorização Residencial da Pressão Arterial (MRPA) fora da meta (média: 146/88mmHg). Na ausência de diabetes, DAOP, insuficiência venosa e outras formas de vasculites, a úlcera foi caracterizada como hipertensiva. O paciente foi então submetido a intervenção comportamental multidimensional como parte de protocolo institucional de medicina do estilo de vida (MEV). O protocolo incluiu telemonitoramento da pressão arterial e da tomada da medicação, além da orientação alimentar e da promoção de atividade física e equilíbrio emocional assistidos via aplicativo gratuito. RESULTADOS: Após duas semanas, obteve-se controle da pressão arterial. Após 6 meses, o paciente apresentou perda de peso de 10 quilos e redução progressiva dos anti-hipertensivos (suspensas hidralazina e clonidina). Cursou com cicatrização completa da UH. Retornou às atividades físicas, manteve adesão ao tratamento e não apresentou recidiva da UH até o momento. CONCLUSÕES: A UH de Martorell é uma condição infrequente e não universalmente reconhecida como entidade clínica independente, não sendo mencionada nos principais textos de referência em HA. No entanto, as características clínicas e histopatológicas dos casos reportados na literatura parecem justificar o diagnóstico, que mais frequentemente é definido por dermatologistas e cirurgiões vasculares. O controle da HA é considerado fundamental para a remissão da úlcera, mas enfrenta o desafio da adesão do paciente ao tratamento. Este é o primeiro relato na literatura a reportar remissão da UH mediante intervenções não farmacológicas fundamentadas na MEV. Independentemente da etiologia, a MEV tem o potencial de atingir a causa primária e de ser benéfica para praticamente todas as formas de úlceras de membros inferiores. Intervenções de MEV deveriam integrar sistematicamente a abordagem terapêutica destes pacientes.

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INTRODUÇÃO E/OU FUNDAMENTO: Menos da metade dos pacientes com hipertensão arterial (HA) atinge sua meta terapêutica. A falta de adesão é apontada como a principal causa de resistência ao tratamento. Entre os motivos pelos quais os pacientes não aderem ao plano terapêutico, a falta de letramento em saúde, os mitos e as crenças limitantes (CLs) desempenham papel determinante. Reconhecer e reverter prontamente tais crenças pode ser decisivo para promover a adesão do paciente e o controle pressórico, mas faltam instrumentos que permitam esse rastreio de forma sistemática na prática clínica. MÉTODOS: Elaboramos um Questionário de cinco perguntas (H-5) a partir de análise exploratória das CLs mais frequentemente observadas em ambulatório de referência no tratamento da HA. Cada pergunta do H-5 explora um conjunto de CLs relativas a uma dimensão específica do tratamento anti-hipertensivo. O questionário foi aplicado a 30 pacientes com diagnóstico de HA resistente consecutivamente atendidos em ambulatório público de referência. As perguntas do H-5 são: 1. O que sentimos quando nossa pressão está alta?; 2. Qual o melhor momento para medir a pressão?; 3. Quando podemos parar de tomar o remédio da pressão?; 4. Porque a pressão alta é um problema?; 5. Qual dessas afirmações é verdadeira sobre o estilo de vida? O formato de avaliação foi por respostas fechadas de múltipla escolha, sendo oferecidas 4 opções por pergunta. RESULTADOS: O H-5 foi aplicado na sala de espera antes da consulta, com tempo médio de execução de 6 minutos. A idade média dos pacientes foi 63,9 ± 9,2 anos (sexo feminino: 83%: IMC: 33,1 ± 6,1). N de anti-hipertensivos: 3,9 ± 1,6; PAS media de consultório: 137 ± 17,4 mmHg); escolaridade: 80% apenas ensino fundamental. A Nota Média foi de 3 acertos em 5 (0= 5%; 2= 20%; 3= 50%; 4= 15%; 5=20%) A taxa de acertos por pergunta (P) foi respectivamente: P1= 20%; P2= 20%; P3= 95%; P4= 80%; P5=85%. Apenas 1 a cada 5 pacientes com HA resistente demonstrou saber que a HA é uma condição assintomática ou que a pressão arterial deve ser medida em condições controladas. CONCLUSÕES: A aplicação do Questionário H-5 foi simples e de rápida execução. 80% dos pacientes apresentou algum grau de crenças limitantes em relação ao tratamento da HA.

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INTRODUÇÃO E/OU FUNDAMENTO: O Hiperaldosteronismo Primário (HP) é a principal causa de hipertensão arterial (HA) endócrina e estima-se que até 20% dos hipertensos resistentes possa ser portador da condição. Indivíduos com HP apresentam um risco cardiovascular (CV) de 4 a 12 vezes mais elevado que portadores de HA primária. Apesar disso, o HP continua largamente subdiagnosticado, em parte pela falta de padronização de triagem, diagnóstico e tratamento. MÉTODOS: A partir de processo de revisão sistemática das diretrizes nacionais e internacionais de HA e HP, elaboramos um algoritmo ilustrando a Jornada Ideal do Paciente com HP. A busca foi realizada em idioma português e inglês na base MEDLINE/PubMed. Selecionamos as publicações dos últimos 5 anos. O processo foi conduzido simultaneamente por dois pesquisadores e os resultados confrontados. RESULTADOS: Um total de 3.476 artigos foram triados para HA e 1.238 para HP. Após revisão e confrontação foram incluídas 22 diretrizes de HA e 9 diretrizes de HP. A partir da análise dos documentos selecionados a Jornada Ideal do Paciente com HP foi segmentada em 7 etapas: 1-Suspeita (definidas as Red Flags); 2-Rastreio (Concentração Plasmática de Aldosterona e Renina ou Atividade da Renina Plasmática); 3-Diagnóstico Laboratorial (critérios e testes confirmatórios); 4-Diagnóstico Anatômico (exames de imagem); 5-Tratamento Cirúrgico (critérios de encaminhamento); 6-Tratamento Clínico (metas terapêuticas e ajuste posológico); 7-Seguimento (critérios e prazos de reavaliação periódica). Com o intuito de acelerar a jornada do paciente, para cada etapa foram definidos gatilhos e ações esperadas, assim como prazos ideais e prazos razoáveis. CONCLUSÕES: Com base nas melhores evidências atualmente disponíveis e a partir de revisão sistemática das diretrizes vigentes, apresentamos uma proposta de Jornada Ideal do Paciente com HP, como modelo para a implantação de serviços especializados para o rastreio, o diagnóstico, o tratamento e o follow-up do HA.

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OBJECTIVES: The aims of this article were to analyse the burden of NCDs and their RFs in the Mercosur countries between 1990 and 2019 and to project mortality trends for 2030. STUDY DESIGN: Epidemiological study of time series. METHODS: The present study used data from the Global Burden of Disease study. The absolute number of deaths, mortality rates, disability-adjusted life years, years of life lost, years lived with disability and the burden of premature mortality by NCD attributable to the RFs were evaluated. Projections were made up to 2030. Age-standardised rates were used to draw comparisons by years and by countries. The analysis was conducted using the RStudio software. RESULTS: Between 1990 and 2019, a decrease was found in the premature mortality rates caused by NCDs in all the countries, except for Paraguay, which remained stable. When analysing premature mortality rates due to NCDs up to 2030, it was predicted that none of the countries would achieve the sustainable development goal of a one-third reduction in premature mortality by NCDs. Regarding the impacts of the RFs for NCDs, smoking, dietary risks, high blood pressure (BP) and high body mass index (BMI) were the main risks attributable to premature deaths due to NCDs. CONCLUSIONS: The results showed that mortality rates are declining in Mercosur countries; however, none of the countries are predicted to achieve the sustainable development goal of a one-third reduction in mortality due to NCDs by 2030. In addition to access to adequate treatment, progress is required in public regulation actions to reduce RFs, such as smoking, dietary risks, high BP and high BMI.

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Physical inactivity is one of the main causes of chronic diseases; however, strenuous exercise can induce immunosuppression. Several studies suggest that moderate amounts of exercise lead to a Th1 response, favoring the resolution of infections caused by intracellular microorganisms, while high volumes of exercise tend to direct the response to Th2, favoring infection by them. Leishmaniasis is a parasitic disease promoted by parasites of the Leishmania genus, with clinical manifestations that vary according to the species of the parasite and the immune response of the host. The experimental Leishmania major-BALB/C mouse model provides a good model for the resistance (Th1 response) or susceptibility (Th2 response) that determines the progression of this infection. The aim of this study was to evaluate the effect of aerobic training at different volumes on modulation of in vitro macrophage infection by L. major, as well as to assess the effect of high volume (HV) aerobic training on the development of L. major in vivo in BALB/c mice. Uninfected animals were submitted to various exercise volumes: none (SED), light (LV), moderate (MV), high (HV), very high (VHV), and tapering (TAP). The macrophages of these animals were infected by L. major and the LV and MV groups showed a decrease in the infection factor, while the VHV showed an increase in the infection factor, when treated with LPS. The cytokine concentration pattern measured in the supernatants of these macrophages suggested a predominant Th1 response profile in the LV and MV groups, while the Th2 profile predominated in the VHV and TAP groups. Groups of BALB/C mice infected with L. major were subjected to high volume (iHV) or non-periodized high volume (iNPHV) exercise or kept sedentary (iSED). The exercised animals suffered a significant increase in injuries caused by the parasites. The animals in the group submitted to high volume exercise (iHV) showed visceralization of the infection. These data strongly suggest that a very high volume of aerobic training increased the susceptibility of BALB/C mice to L. major infection, while moderate distribution of training loads promoted immunological balance, better controlling the infection by this parasite.

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A good understanding of the immunological correlates of protective immunity is an important requirement for the development of effective vaccines against malaria. However, this concern has received little attention even in the face of two decades of intensive vaccine research. Here, we review the immune response to blood-stage malaria, with a particular focus on the type of vaccine most likely to induce the kind of response required to give strong protection against infection.

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AIM: To analyse the effect of calcium hydroxide paste, endodontic irrigants and time of application on the bond strength of fibre posts to root canal dentine. METHODOLOGY: Seventy bovine incisors were divided into 7 groups according to removal of calcium hydroxide and distilled water (CHW) (immediate - I; 21 days - 21 days; 6 months - 6 months) and endodontic irrigant (1% sodium hypochlorite - SH; 1% sodium hypochlorite + 17% EDTA - SHE). Fibre posts were cemented (RelyX U100), after which the roots were serially sectioned and submitted to a micro-push-out test. Data were analysed using two-way anova followed by the Tukey's and the Dunnett's tests (α = 0.05). RESULTS: The CHW groups were not significantly different from the control group in 13 of the 18 associated factors (P > 0.05). There were significant reductions in bond strength in the cervical (P = 0.0216) and middle (P = 0.0017) thirds of the root at 6 months in groups irrigated with SH. Irrigation with SHE reduced the bond strength significantly in the middle (P = 0.0488) and apical (P = 0.0252) thirds of the roots in the immediate groups and in the middle third (P = 0.0287) in the 21-day group. Bond strength was greater in the cervical than in the apical thirds of all immediate and 21-day groups (P < 0.05). CONCLUSIONS: Bond strength of groups that received CH paste was similar to that found in the control group in 13 of the 18 associated factors. EDTA and SH reduced bond strength in specimens in the immediate (middle and apical thirds) and 21-day (middle third) groups. There was a significant reduction in bond strength in the groups irrigated with SH and tested at 6 months (cervical and middle thirds). There was a predominance of adhesive failures between resin cement and dentine in all groups.

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Galectins are evolutionarily conserved glycan-binding proteins with pleiotropic roles in innate and adaptive immune responses. Galectin-3 has been implicated in several immunological processes as well as in pathogen recognition through specific binding to glycosylated receptors on the surface of host cells or microorganisms. In spite of considerable evidence supporting a role for galectin-3 in host-pathogen interactions, the relevance of this lectin in the regulation of the host defence mechanisms in vivo is poorly understood. In this study, we analysed the impact of galectin-3 deficiency during infection with three distinct species of rodent malaria parasites, Plasmodium yoelii 17XNL, Plasmodium berghei ANKA and Plasmodium chabaudi AS. We found that galectin-3 deficiency showed a marginal effect on the course of parasitaemia during P. chabaudi infection, but did not alter the course of parasitaemia during P. berghei infection. However, lack of galectin-3 significantly reduced P. yoelii parasitaemia. This reduced parasitaemia in Lgals3(-/-) mice was consistent with higher titres of anti-P. yoelii MSP1(19) IgG2b isotype antibodies when compared with their wild-type counterparts. Our results reflect the complexity and singularity of host-pathogen interactions, indicating a species-specific role of endogenous galectin-3 in the control of parasite infections and the modulation of antibody responses.

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When ozone is used during caries treatment, bond strength can be compromised by the release of oxygen. The use of antioxidant agents neutralizes the free oxygen. The aim of this study was to evaluate the effects of ozone and sodium ascorbate on resin-dentin microtensile bond strength (µTBS). Forty human third molars were divided into four groups: Group 1, not treated with ozone; Group 2, ozone application followed by acid etching; Group 3, acid etching followed by ozone application; and Group 4, ozone and application of sodium ascorbate. Bonded beams (1.0 mm(2)) were tested under tension (0.5 mm min(-1)). The µTBS values were analyzed using one-way analysis of variance (ANOVA) and the Tukey test (p=0.05). All beams that fractured were analyzed under stereomicroscopy (40×). Group 1 had significantly higher µTBS values than Group 2 or 3. The µTBS values of Groups 1 and 4 were similar and higher than those of Group 2. The use of ozone in Group 2 resulted in lower values of µTBS in all conditions evaluated. The predominant failure mode was adhesive. The application of ozone decreased the µTBS of the dentin-composite resin interface. These values were reversed when compared with Groups 1 and 2 when sodium ascorbate was used.

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AIMS: The initial colonization of the tooth by streptococci involves their attachment to adsorbed components of the acquired pellicle. Avoiding this adhesion may be successful in preventing caries at early stages. Salivary mucins are glycoproteins that when absorbed onto hydroxyapatite may provide binding sites for certain bacteria. Algal lectins may be especially interesting for oral antiadhesion trials because of their great stability and high specificity for mucins. This work aimed to evaluate the potential of two algal lectins to inhibit the adherence of five streptococci species to the acquired pellicle in vitro. METHODS AND RESULTS: The lectins used were extracted from Bryothamnion triquetrum (BTL) and Bryothamnion seaforthii (BSL). Fluorescence microscopy was applied to visualize the ability of fluorescein isothiocyanate-labelled lectins to attach to the pellicle and revealed a similar capability for both lectins. Streptococcal adherence assays were performed using saliva-coated microtitre plates. BSL inhibited more than 75% of Streptococcus sanguis, Streptococcus mitis, Streptococcus sobrinus and Streptococcus mutans adherence, achieving 92% to the latter. BTL only obtained statistically significant results on S. mitis and S. sobrinus, whose adherence was decreased by 32.5% and 54.4%, respectively. CONCLUSION: Algal lectins are able to inhibit streptococcal adherence. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results support the proposed application of lectins in antiadhesion therapeutics.

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In this work assays involving chlorinated water samples, which were previous spiked with humic substances or algae blue green and following the production of the THMs for 30 days is described. To implement the assays, five portions of 1,000 ml of water were stored in glass bottles. The water samples were treated with solutions containing 2, 3, 4 and 5 mg l(-1) chlorine. The samples aliquots (60 ml) were transferred into the glass vials, 10 ml were removed to have a headspace and 100 microl of the 10 mg l(-1) pentafluortoluene bromide solution was added to each vial. The extraction step was performed by adding 10 g of Na(2)SO(4) followed by 5 ml of n-pentane. The vials were stopped with a TFE-faced septum and sealed with aluminum caps. The generated THMs were determined by gas chromatography with electron capture detector using reference solutions with concentration ranging from 8 to 120 microg l(-1) THMs. Three assays were monitored during 30 days and chloroform was the predominant compound found in the water samples, while other species of THMs were not detected. The results showed that when the chlorine concentration was increased in water samples containing algae the concentration of THM varied randomly. Nevertheless, in water samples containing humic substances the increase of the THM concentration presented a relationship with the chlorine concentration. It was also observed that chloroform concentration increased with the elapsed time up to one and six days to water samples spiked with humic substances and algae blue green, respectively and decreased along 30 days. By other hand, assays performed using water samples containing decanted algae material showed that THM was not generated by the chlorine addition.

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The aqueous extract of Casearia sylvestris was tested in cortical membrane preparations. C. sylvestris was obtained commercially from two different sources, designated as Sample A and Sample B. The enzymes studied in this work were NTPDase-like, 5'-Nucleotidase, Na(+)/K(+)-ATPase and acetylcholinesterase (AChE). Adult rats received aqueous extracts from C. sylvestris in a dose of 20mg/kg body wt. daily for a 75-day-period, by oral administration (gavage). Our study showed that this treatment caused an inhibition of NTPDase-like activity with both, ATP (19.41% with Sample A and 25.03% with Sample B) and ADP (41.57% with Sample A and 31.20% with Sample B) as substrates. This treatment also caused an inhibition of 5'-nucleotidase activity (28.34% with Sample A and 31.46% with Sample B) and Na(+)/K(+)-ATPase (25.08% with Sample A and 24.81% with Sample B). The rate of acetylcholine degradation was reduced, as shown by the inhibition of AChE (31.65% and 26.74%, Samples A and B, respectively). These results suggest that extracts of C. sylvestris can cause neurochemical alterations in the purinergic and cholinergic systems of the central nervous system.

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Glycosylphosphatidylinositols (GPIs) are found in the outer cell membranes of all eukaryotes. GPIs anchor a diverse range of proteins to the surface of Plasmodium falciparum, but may also exist free of protein attachment. In vitro and in vivo studies have established GPIs as likely candidate toxins in malaria, consistent with the prevailing paradigm that attributes induction of inflammatory cytokines, fever and other pathology to parasite toxins released when schizonts rupture. Although evolutionarily conserved, sufficient structural differences appear to exist that impart upon plasmodial GPIs the ability to activate second messengers in mammalian cells and elicit immune responses. In populations exposed to P. falciparum, the antibody response to purified GPIs is characterised by a predominance of immunoglobulin (Ig)G over IgM and an increase in the prevalence, level and persistence of responses with increasing age. It remains unclear, however, if these antibodies or other cellular responses to GPIs mediate anti-toxic immunity in humans; anti-toxic immunity may comprise either reduction in the severity of disease or maintenance of the malaria-tolerant state (i.e. persistent asymptomatic parasitaemia). P. falciparum GPIs are potentially amenable to specific therapeutic inhibition and vaccination; more needs to be known about their dual roles in malaria pathogenesis and protection for these strategies to succeed.

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We have previously reported that infection with Plasmodium yoelii, Plasmodium chabaudi, or injection of extracts from malaria-parasitized red blood cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in streptozotocin (STZ)-diabetic mice. P yoelii glycosylphosphatidylinositols (GPIs) were extracted in chloroform:methanol:water (CMW) (10:10:3), purified by high-performance thin layer chromatography (HPTLC) and tested for their insulin-mimetic activities. The effects of P yoelii GPIs on blood glucose were investigated in insulin-resistant C57BL/ks-db/db diabetic mice. A single intravenous injection of GPIs (9 and 30 nmol/mouse) induced a significant dose-related decrease in blood glucose (P < .001), but insignificantly increased plasma insulin concentrations. A single oral dose of 2.7 micromol GPIs per db/db mouse significantly lowered blood glucose (P < .01). P yoelii GPIs in vitro (0.062 to 1 micromol/L) significantly stimulated lipogenesis in rat adipocytes in a dose-dependent manner both in the presence and absence of 10(-8) mol/L insulin (P < .01). P yoelii GPIs stimulated pyruvate dehydrogenase phosphatase (PDH-Pase) and inhibited both cyclic adenosine monophosphate (cAMP)-dependent protein kinase A and glucose-6-phosphatase (G6Pase). P yoelii GPIs had no effect on the activity of the gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase) and phosphoenolpyruvate carboxykinase (PEPCK). This is the first report of the hypoglycemic effect of P yoelii GPIs in murine models of type 2 diabetes. In conclusion, P yoelii GPIs demonstrated acute antidiabetic effects in db/db mice and in vitro. We suggest that P yoelii GPIs, when fully characterized, may provide structural information for the synthesis of new drugs for the management of diabetes.

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This open-label study evaluated the effects on body fat of the use of a low-dose oral contraceptive (gestodene75/EE20) in a group of 61 women (OC-U group) as compared to a nonuser group (OC-N group) of 51 women who did not receive an oral contraceptive. Weight, body mass index (BMI), waist-over-hip ratio and body composition data, obtained by bioelectrical impedance [percentages of body fat (%FAT), water (%TBW) and lean mass (%FFM)], were assessed before and after six treatment cycles. Baseline OC-U group weight, BMI, %FAT, %TBW and %FFM did not differ from the OC-N group, either at baseline or at the end of the study, and did not significantly change within each group during the study. Also, there was no modification of fat distribution in either group. Among women in the OC-U group, there was a slight increase in total cholesterol levels and a trend towards higher triglycerides levels. No changes were detected in blood pressure. In conclusion, this low-dose oral contraceptive did not affect weight or body composition. Thus, our data suggest that gestodene75/EE20 represents an appropriate OC choice and may enhance compliance of women who mistakenly believe that the use of oral contraceptives always leads to weight gain.

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Sterilization by gamma radiation is a method often used for bone and extracted teeth banking. The bond strength of human dentin submitted to gamma rays has not been reported. Therefore, the aim of this study was to assess the effect of gamma radiation on dentin shear bond strength and morphology. The roots were removed from extracted human bicuspids and their crowns divided into two groups: an untreated control and crowns submitted to gamma radiation sterilization. The crowns were mounted in epoxy resin and the buccal enamel removed exposing the subjacent dentin. SBMPPlus adhesive system was applied to a 3-mm diameter area after 15 s of 35% phosphoric acid etching. The samples were mounted in composite resin cylinders and stored in distilled water at 37 degrees C for 24 h until the shear test. Dental fragments from both groups were prepared for SEM analysis. There was no statistically significant difference between the results of the shear test for the two groups according to the Tukey test (p > 0.05). Scanning electron micrographs also did not show alterations. These results indicate that gamma radiation neither affected the shear bond strength of SBMPPlus nor altered the dentin surface morphology.

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Spontaneous bacterial peritonitis (SBP) is a frequent infection in cirrhotic patients with ascites, with a poor prognosis. The aims of this study were to determine the long-term survival of cirrhotic patients with SBP treated with ceftriaxone and to identify predictive factors related to survival. We studied 47 first episodes of SBP treated with ceftriaxone with a mean follow-up of 272 days. Nineteen variables were recorded to evaluate their relation to survival. The most frequent organism that caused SBP was Escherichia coli (40%). Spontaneous bacterial peritonitis resolution was achieved in 67% of patients. After resolution, SBP recurrence was observed in 44% of patients. The cumulative probability of survival was 68.1% at 1 month and 30.8% at 6 months. After uni-and multivariate analyses of all cases, SBP resolution ( p = 0.0001) and international normalized ratio (INR) ( p = 0.0057) were found to be related to survival. Another analysis performed after SBP resolution and SBP recurrence showed that ascitic fluid-positive culture ( p = 0.0344) and INR ( p = 0.0218) had statistical significance as variables predictive of long-term survival. We conclude that the survival of cirrhotic patients is very short after the first episode of SBP, a fact probably related to advanced liver disease, as liver dysfunction (INR) is the most important factor related to long-term patient survival.

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We have previously shown that infection with Plasmodium yoelii malaria or injection of extracts from malaria-parasitized red cells induces hypoglycemia in normal mice and normalizes the hyperglycemia in mice made moderately diabetic with streptozotocin. Inositol phosphoglycans (IPGs) are released outside cells by hydrolysis of membrane-bound glycosylphosphatidylinositols (GPIs), and act as second messengers mediating insulin action. The C57BL/Ks-db/db and C57BL/6J-ob/ob mice offer good models for studies on human obesity and Type 2 diabetes. In the present study, we show that a single iv injection of IPG-A or IPG-P extracted from P. yoelii significantly (P < 0.02) lowers the blood glucose in STZ-diabetic, db/db, and in ob/ob mice for at least 4--6 h. Using rat white adipocytes, IPG-P increased lipogenesis by 20--30% in the presence and absence of maximal concentrations of insulin (10(-8) M) (P < 0.01) and stimulated pyruvate dehydrogenase (PDH) phosphatase in a dose-related manner. Both IPG-A and IPG-P inhibited c-AMP-dependent protein kinase (PKA) in a dose-related manner. Compositional analysis of IPGs after 24 h hydrolysis revealed the presence of myo-inositol, phosphorus, galactosamine, glucosamine, and glucose in both IPG-A and IPG-P. However, hydrolysis of IPGs for 4 h highlighted differences between IPG-A and IPG-P. There are some functional similarities between P. yoelii IPGs and those previously described for mammalian liver. However, this is the first report of the hypoglycemic effect of IPGs in murine models of Type 2 diabetes. We suggest that IPGs isolated from P. yoelii, when fully characterized, may provide structural information for the synthesis of new drugs for the management of diabetes mellitus.

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A case of gingival erosive lichen planus is presented with special emphasis on its clinical and microscopic characteristics. The differential diagnosis and the controversy associated with the malignant potential of oral lichen planus is also discussed.

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The early role of natural killer cells and gamma delta T cells in the development of protective immunity to the blood stage of nonlethal Plasmodium yoelii infection was studied. Splenic cytokine levels were measured 24 h after infection of natural killer cell-depleted immunodeficient and littermate mice or transiently T-cell-depleted normal mice. Splenic gamma interferon levels were significantly increased above background in immunodeficient and littermate mice 24 h after infection. Depletion of natural killer cells resulted in markedly depressed gamma interferon levels and poor control of parasitemia, particularly in severe combined immunodeficient mice. In the littermates, gamma interferon levels were partially reduced, but parasitemias were resolved normally. However, in athymic mice, natural killer cell depletion had no effect on gamma interferon production. Levels of tumor necrosis factor alpha were increased in all animals 24 h after infection, and responses were not affected by natural killer cell depletion. However, in T-cell-depleted animals, both gamma interferon and tumor necrosis factor alpha levels were decreased 24 h after infection, and depleted mice were unable to control their parasitemia. These results suggest that the early production of both cytokines is important in the early control of parasitemia and that both natural killer and gamma delta T cells contribute equally towards their production. The data also suggest that the subsequent resolution of infection requires early production of gamma interferon, which might act by switching on the appropriate T-helper-cell subsets and other essential parasitotoxic effector mechanisms.

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