Native/citrullinated LL37-specific T-cells help autoantibody production in Systemic Lupus Erythematosus.

LL37 exerts a dual pathogenic role in psoriasis. Bound to self-DNA/RNA, LL37 licenses autoreactivity by stimulating plasmacytoid dendritic cells-(pDCs)-Type I interferon (IFN-I) and acts as autoantigen for pathogenic Th17-cells. In systemic lupus erythematosus (SLE), LL37 also triggers IFN-I in pDCs and is target of pathogenic autoantibodies. However, whether LL37 activates T-cells in SLE and how the latter differ from psoriasis LL37-specific T-cells is unknown. Here we found that 45% SLE patients had circulating T-cells strongly responding to LL37, which correlate with anti-LL37 antibodies/disease activity. In contrast to psoriatic Th17-cells, these LL37-specific SLE T-cells displayed a T-follicular helper-(TFH)-like phenotype, with CXCR5/Bcl-6 and IL-21 expression, implicating a role in stimulation of pathogenic autoantibodies. Accordingly, SLE LL37-specific T-cells promoted B-cell secretion of pathogenic anti-LL37 antibodies in vitro. Importantly, we identified abundant citrullinated LL37 (cit-LL37) in SLE tissues (skin and kidney) and observed very pronounced reactivity of LL37-specific SLE T-cells to cit-LL37, compared to native-LL37, which was much more occasional in psoriasis. Thus, in SLE, we identified LL37-specific T-cells with a distinct functional specialization and antigenic specificity. This suggests that autoantigenic specificity is independent from the nature of the autoantigen, but rather relies on the disease-specific milieu driving T-cell subset polarization and autoantigen modifications.

Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury.

BACKGROUND: Circulating cell-free DNA (cfDNA) is not found in healthy subjects, but is readily detected after thermal injury and may contribute to the risk of multiple organ failure. The hypothesis was that a postburn reduction in DNase protein/enzyme activity could contribute to the increase in cfDNA following thermal injury. METHODS: Patients with severe burns covering at least 15 per cent of total body surface area were recruited to a prospective cohort study within 24 h of injury. Blood samples were collected from the day of injury for 12 months. RESULTS: Analysis of blood samples from 64 patients revealed a significant reduction in DNase activity on days 1-28 after injury, compared with healthy controls. DNase protein levels were not affected, suggesting the presence of an enzyme inhibitor. Further analysis revealed that actin (an inhibitor of DNase) was present in serum samples from patients but not those from controls, and concentrations of the actin scavenging proteins gelsolin and vitamin D-binding protein were significantly reduced after burn injury. In a pilot study of ten military patients with polytrauma, administration of blood products resulted in an increase in DNase activity and gelsolin levels. CONCLUSION: The results of this study suggest a novel biological mechanism for the accumulation of cfDNA following thermal injury by which high levels of actin released by damaged tissue cause a reduction in DNase activity. Restoration of the actin scavenging system could therefore restore DNase activity, and reduce the risk of cfDNA-induced host tissue damage and thrombosis.

ANTECEDENTES: El ADN libre de las células circulantes (circulating cell-free DNA, cfDNA) no se encuentra en sujetos sanos, pero se detecta fácilmente después de una lesión térmica y puede contribuir al riesgo de fallo multiorgánico. La hipótesis fue que una disminución en la actividad de la proteína/enzima ADNasa tras la lesión térmica podría contribuir a la elevación del cfDNA que ocurre tras la misma. MÉTODOS: Los pacientes con quemaduras graves con una extensión ≥ 15% del área de superficie corporal total (total body surface area, TBSA) se incluyeron en un estudio prospectivo de cohortes durante las primeras 24 horas posteriores a la lesión. Se recogieron muestras de sangre desde el día de la lesión hasta los 12 meses posteriores a la misma. RESULTADOS: El análisis de muestras de sangre de 64 pacientes reveló una reducción significativa de la actividad de la ADNasa en los días 1 a 28 después de la lesión, en comparación con los controles sanos. Los niveles de proteína ADNasa no se vieron afectados, lo que sugiere la presencia de un inhibidor enzimático. Un análisis adicional reveló que la actina (un inhibidor de la ADNasa) estaba presente en las muestras de suero de los pacientes, pero no en los controles, y las concentraciones de la gelsolina, proteína que causa la disociación de la actina, y la proteína de unión a la vitamina D se redujeron significativamente después de la lesión térmica. En un estudio piloto de 10 pacientes con politrauma por lesiones militares, la administración de hemoderivados produjo un aumento en la actividad de la ADNasa y de los niveles de gelsolina. CONCLUSIÓN: Este estudio sugiere un nuevo mecanismo biológico para la acumulación de cfDNA después de una lesión térmica, por el cual los altos niveles de actina liberada por el tejido dañado causarían una reducción en la actividad de la ADNasa. La restauración del sistema eliminador de actina podría, por lo tanto, restaurar la actividad de la ADNasa y reducir el riesgo de daño tisular y trombosis en el huésped inducido por el cfDNA.

Miopatia White Striping em diferentes linhagens de frangos de corte e suas consequências sobre a composição e a qualidade da carne / The White Striping myopathy in different broiler strains and its influence on composition and meat quality

Avaliou-se a incidência da miopatia White Striping (WS) em três linhagens de frangos de corte machos e suas consequências sobre a composição química e a qualidade física da carne. Para determinação das porcentagens de incidência dos diferentes graus da miopatia WS (normal, moderada e severa) nas linhagens, foi utilizado um delineamento inteiramente ao acaso (DIC), com três tratamentos (linhagens A, B e C) e cinco repetições de 300 peitos cada. Para as variáveis químicas e físicas, utilizou-se um DIC em esquema fatorial 3 x 3 (três linhagens x três níveis de WS), com 15 repetições cada. Os dados foram submetidos à análise de variância e, em casos de diferenças significativas, utilizou-se o teste de Tukey (P≤0,05). As aves da linhagem A apresentaram 84,81% de peitos classificados como normais e 9,91% de peitos classificados como moderados, valores respectivamente maiores e menores que nas duas demais linhagens. Os peitos classificados com miopatia WS severa foram mais pesados e apresentaram maiores porcentagens de lipídios e umidade, e menor concentração de proteína bruta. As concentrações de colágeno total, termo solúvel e insolúvel variaram com o nível de acometimento por WS nos filés, com comportamento específico para cada linhagem.(AU)

The incidence of the White Striping (WS) myopathy in three male broiler strains and its consequences on the chemical composition and physical quality of the meat was evaluated. A completely randomized design (DIC) with three treatments (strains A, B and C) and five replicates of 300 breasts each were used to determine the incidence rates of the different degrees of WS myopathy (normal, moderate and severe) in each strain. For the chemical and physical variables, a 3 X 3 factorial scheme was used (three strains X three WS levels), with 15 replicates. The data were submitted to ANOVA and in cases of significant differences the Tukey test (P< 0.05) was used.The A strain chickens presented 84.81% of breasts classified as normal and 9.91% of breasts classified as moderate, respectively higher and lower values than in the other two strains. Breasts classified with severe WS myopathy were heavier and had higher percentages of lipids and moisture, and lower concentration of crude protein. However, the concentrations of total, soluble and insoluble collagen had interaction effects between lineage and WS level in the fillets, and therefore, the same behavior was not observed in the samples of the different strains.(AU)

Post-Streptococcal Uveitis: a Rare Entity.

Without appropriate treatment, Group A streptococcal infections can lead to post-streptococcal syndrome, including post-streptococcal uveitis. This should be kept in mind in young patients with acute bilateral non-granulomatous anterior uveitis, in order to avoid ocular and systemic complications. We report two cases of bilateral post-streptococcal anterior uveitis, in young men, of respectively 20 and 16 years old, that presented to Jules Gonin Eye Hospital.

Magnetorheological finishing of chemical-vapor deposited zinc sulfide via chemically and mechanically modified fluids.

We describe the anisotropy in the material removal rate (MRR) of the polycrystalline, chemical-vapor deposited zinc sulfide (ZnS). We define the polycrystalline anisotropy via microhardness and chemical erosion tests for four crystallographic orientations of ZnS: (100), (110), (111), and (311). Anisotropy in the MRR was studied under magnetorheological finishing (MRF) conditions. Three chemically and mechanically modified magnetorheological (MR) fluids at pH values of 4, 5, and 6 were used to test the MRR variations among the four single-crystal planes. When polishing the single-crystal planes and the polycrystalline with pH 5 and pH 6 MR fluids, variations were found in the MRR among the four single-crystal planes and surface artifacts were observed on the polycrystalline material. When polishing the single-crystal planes and the polycrystalline with the modified MR fluid at pH 4, however, minimal variation was observed in the MRR among the four orientations and a reduction in surface artifacts was achieved on the polycrystalline material.

Incidence and factors associated with medication nonadherence in patients with mental illness: a cross-sectional study.

BACKGROUND: In spite of the progress made in the treatment of psychiatric disorders during the last few decades, nonadherence continues to be a frequent phenomenon, often associated with potentially severe clinical consequences and increased health-care costs. There are numerous factors associated with medication nonadherence in patients with mental illness. The aim of the study was to determine the incidence and factors associated with medication nonadherence among psychiatric outpatients. MATERIALS AND METHODS: A cross-sectional study was carried out in the outpatient psychiatric department of an Indian tertiary care private hospital over a period of 1 year. Patients aged 18 years and above who presented with mental illness as diagnosed by the International Classification of Diseases (ICD)-10 and who were receiving at least one psychotropic medication for at least 1 month were included in the study. Medication adherence was assessed using the Medication Adherence Rating Scale (MARS). RESULTS: Of the 400 patients, 172 (43%) were nonadherent to their prescribed medications. There is a statistically significant association between the education (P = 0.001), number of drugs (P = 0.002), family income (P = 0.013), and nonadherence. Among the 172 patients, 33.5 % were nonadherent to their therapy due to patient-related factors followed by drug-related factors (32%) and disease-related factors (31%). CONCLUSION: The overall incidence of medication nonadherence in patients with mental illness was 43%. Numerous factors contributed to medication nonadherence. Strategies need to be developed and implemented to enhance medication adherence, and thereby achieve a better therapeutic outcome in patients with mental illness.

First record of Dero (Aulophorus) bimagnasetus Harman (Oligochaeta) from Brazil and habitat characteristics.

Annelid worms represent a significant part of freshwater benthic communities worldwide and Oligochaeta is a particularly species-rich group. Dero (A) bimagnasetus (Naididae) previously found and described from a small marsh in Surinam in 1974, has now been found for the first time in Barra Lake, MG, Brazil. Due to the scarce biological data and absence of ecological information in the literature regarding this species we are presenting morphological information on the specimens obtained and the physical and chemical characteristics of the habitat they were found. This species occurred only in the littoral zone of Barra Lake, in muddy, low oxygen, low conductivity and low organic matter sediment. The four individuals collected ranged 3.17-4.15 mm total length; 0.25 - 0.26 mm body width and 0.16-0.21 mm3 total volume. Considering the present anthropic pressures on freshwater biota and fast biodiversity losses worldwide it is now recognized that attention must be paid to low abundance species and the urgency for preservation of their habitats.

Deployed research.

The Role 3 Medical Treatment Facility (Field Hospital) in Camp Bastion (R3 Bastion) is acknowledged to be one of the busiest dedicated trauma facilities in the world. Casualties typically present with severe injuries and in physiological extremis. These casualties form a unique cohort representing the most relevant population to evaluate the effectiveness of treating battlefield injuries as academic clinicians and scientists interested in trauma seek to improve outcomes for such patients in the future. This article describes four separate but related research projects that have been undertaken in Camp Bastion, Afghanistan, over the last year. They traverse the spectrum of clinical research, ranging from data collection to a randomised control trial. The aim is to discuss some of the problems encountered and the solutions that made it possible to undertake research in a theatre of operations, thereby providing a starting point for others who may wish to initiate research in a similar environment.

Benthic macroinvertebrates of a tropical lake: Lake Caçó, MA, Brazil.

Benthic communities are highly relevant in the study of aquatic ecosystems, both for their role in the functioning of the ecosystem and also as markers or indicators of paleo-conditions. Their distribution, as in other communities, is conditioned by abiotic and biotic factors and to their interactions, which determine the structure of the community that is established. The aim of this study was to determine the taxonomic composition, abundance and spatial distribution of the benthic community, by collecting at 20 sampling sites in Caçó Lake (State of Maranhão, Brazil). Seasonal variation in these community parameters was analysed and related to the seasonal displacement of the Intertropical Convergence Zone. The results indicated that changes occur in the taxa richness, diversity and density of the benthic species of this lake that are mainly related to seasonality. All those parameters were higher in the dry than in the rainy period. The family Chironomidae (Diptera, Insecta) was the most important component of the community, representing approximately 50% of the total benthic fauna of the lake. The identification of the Chironomidae currently occurring in Lake Caçó is relevant, even at the genus level, considering the fact that this group produces fossilizing remains and could perhaps be good paleolimnological and paleoclimatic tracers that could be used to make inferences on past lake and climate conditions.

Benthic macroinvertebrates of a tropical lake: lake Caçó, MA, Brazil / Macroinvertebrados bentônicos de um lago tropical: lago Caço, MA, Brasil

Benthic communities are highly relevant in the study of aquatic ecosystems, both for their role in the functioning of the ecosystem and also as markers or indicators of paleo-conditions. Their distribution, as in other communities, is conditioned by abiotic and biotic factors and to their interactions, which determine the structure of the community that is established. The aim of this study was to determine the taxonomic composition, abundance and spatial distribution of the benthic community, by collecting at 20 sampling sites in Caçó Lake (State of Maranhão, Brazil). Seasonal variation in these community parameters was analysed and related to the seasonal displacement of the Intertropical Convergence Zone. The results indicated that changes occur in the taxa richness, diversity and density of the benthic species of this lake that are mainly related to seasonality. All those parameters were higher in the dry than in the rainy period. The family Chironomidae (Diptera, Insecta) was the most important component of the community, representing approximately 50 percent of the total benthic fauna of the lake. The identification of the Chironomidae currently occurring in Lake Caçó is relevant, even at the genus level, considering the fact that this group produces fossilizing remains and could perhaps be good paleolimnological and paleoclimatic tracers that could be used to make inferences on past lake and climate conditions.

As comunidades bentônicas são relevantes nos ecossistemas aquáticos devido ao seu papel no seu funcionamento e também como marcadores ou indicadores de paleocondições. Sua distribuição, similarmente à de outras comunidades, é condicionada por fatores abióticos e bióticos e pela interação entre eles, determinando a estrutura da comunidade que se estabelecerá. O objetivo do presente trabalho foi determinar a composição taxonômica, a abundância e a distribuição espacial da comunidade bentônica, amostrando-se em 20 pontos na lagoa do Caçó (Estado do Maranhão, Brasil). As variações sazonais nas características desta comunidade foram analisadas e relacionadas ao deslocamento sazonal da Zona de Convergência Intertropical. Os resultados indicaram que ocorrem mudanças na riqueza de taxons, diversidade e densidade da comunidade bentônica deste lago que são principalmente relacionadas à sazonalidade. Todas as variáveis analisadas foram maiores no período seco do que no chuvoso. Os organismos pertencentes à família Chironomidae (Diptera, Insecta) foram os mais importantes componentes da comunidade, representando aproximadamente 50 por cento do total da fauna. A identificação dos Chironomidae atualmente presentes no Lago Caçó, mesmo em nível de gênero, é relevante, considerando-se o fato de que as larvas deste grupo produzem remanescentes fósseis que podem ser bons traçadores paleolimnológicos e paleoclimáticos, podendo ser utilizados para fazer inferências sobre as condições passadas neste lago e no clima regional.

A phase II study of weekly paclitaxel in elderly patients with advanced non-small cell lung cancer.

PURPOSE: Our aim was to evaluate the efficacy, toxicity, and pharmacokinetic behavior of single-agent paclitaxel given weekly to elderly patients with lung cancer. EXPERIMENTAL DESIGN: Previously untreated patients with stage IIIB/IV non-small cell lung cancer were eligible for the study if they were at least 70 years of age and had preserved organ function. Paclitaxel was administered over 1 h at a dose of 90 mg/m(2) for 6 consecutive weeks on an 8-week cycle. The pharmacokinetics of paclitaxel were assessed during the first and sixth week of therapy in a subgroup of eight patients. RESULTS: A total of 35 patients (median age, 76 years; range, 70-85) were enrolled. The overall response rate was 23%. Median time to failure was 5.2 months, whereas the median survival time was 10.3 months. Survival rates after 1 and 2 years were 45 and 22%, respectively. Grade 3/4 toxicities included neutropenia (5.8%), hyperglycemia (17.6%), neuropathy (5.8%), and infection (8.8%). Two patients died from treatment-related toxicity. There was no significant difference (P = 0.18) between the total body clearance of paclitaxel on the first (17.4 +/- 2.9 liters/h/m(2), mean +/- SD) and sixth (15.8 +/- 4.1 liters/h/m(2)) week of therapy. CONCLUSION: Paclitaxel administered as a weekly 1-h infusion at a dose of 90 mg/m(2) is a safe and effective therapy for elderly patients with advanced non-small cell lung cancer. Its pharmacokinetics in elderly patients do not appear to differ from historical data for younger patients, and there was no suggestion of a change in drug clearance after repeated weekly dosing.

A phase II trial of the cyclin-dependent kinase inhibitor flavopiridol in patients with previously untreated stage IV non-small cell lung cancer.

PURPOSE: Flavopiridol is a potent cyclin-dependent kinase inhibitor with preclinical activity against non-small cell lung cancer (NSCLC), inhibiting tumor growth in vitro and in vivo by cytostatic and cytotoxic mechanisms. A Phase II trial was conducted to determine the activity and toxicity of flavopiridol in untreated patients with metastatic NSCLC. EXPERIMENTAL DESIGN: A total of 20 patients were treated with a 72-h continuous infusion of flavopiridol every 14 days at a dose of 50 mg/m(2)/day and a concentration of 0.1-0.2 mg/ml. Dose escalation to 60 mg/m(2)/day was permitted if no significant toxicity occurred. Response was initially assessed after every two infusions; patients treated longer than 8 weeks were then assessed after every four infusions. Plasma levels of flavopiridol were measured daily during the first two infusions to determine steady-state concentrations. RESULTS: This study was designed to evaluate a total of 45 patients in two stages. However, because no objective responses were seen in the first 20 patients, the early-stopping rule was invoked, and patient accrual was halted. In four patients who received eight infusions, progression was documented at 15, 20, 40, and 65 weeks, respectively. The most common toxicities included grade 1 or 2 diarrhea in 11 patients, asthenia in 10 patients, and venous thromboses in 7 patients. The mean +/- SD steady-state concentration of drug during the first infusion was 200 +/- 89.9 nM, sufficient for cytostatic effects in in vitro models. CONCLUSIONS: At the current doses and schedule, flavopiridol does not have cytotoxic activity in NSCLC, although protracted periods of disease stability were observed with an acceptable degree of toxicity.

Role of smooth muscle cell membrane potential in neointima formation in arteries of spontaneously hypertensive rats.

Based on observations that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) have altered resting potentials as well as abnormal cell proliferation rates, neointima formation after controlled balloon injury was compared in arteries from SHR and Wistar Kyoto rats (WKY). SHR aortic VSMC showed hyperpolarized resting membrane potentials (-93+/-8 mV) when compared to those from WKY (-61+/-6 mV). Histomorphometric analysis of cross sections from aortic segments submitted to balloon injury showed reduced neointima formation in SHR (neointima/media ratio: 0.04+/-0.03) as compared to WKY (0.2+/-0.1). On the other hand, in injured carotid arteries, neointima formation was more extensive in SHR (neointima/media ratio 5.0+/-0.9) than in WKY (0.8+/-0.7), leading in most cases to luminal occlusion. Measurements of VSMC resting potential showed that carotid artery cells from SHR were depolarized with respect to those from WKY (-46+/-4 vs. -69+/-5 mV, respectively). The results demonstrate an inverse relationship between VSMC membrane polarization and neointima formation in SHR arteries, suggesting that genetic modifications in SHR determine a dysfunctional cellular physiology that may influence cell proliferation subsequent to injury.

Oestrous cycle and pregnancy alter the reactivity of the rat uterine vasculature.

Isolated uterine vascular beds from virgin and pregnant rats were used to assess vascular reactivity and the ability of nitric oxide (NO), prostanoids and endothelium-derived hyperpolarizing factor (EDHF) to modulate these responses. One uterine horn from female rats in each oestrous cycle day and gestation day 17 was removed and perfused with physiological saline solution. Tone was induced with cirazoline (1 micromol/l), and concentration-response curves to acetylcholine (ACh) generated. Responsiveness to ACh was tested in the presence of N-nitro-L-arginine (L-NA), ibuprofen (IBU) and tetrabutylammonium (TBA), to inhibit NO synthase, cyclo-oxygenase and K+ channels respectively. Cirazoline-induced tone was smaller in the pregnant compared with the proestrous group. Sensitivity to ACh was cycle day and pregnancy dependent with pregnant > dioestrous day-1 > dioestrous day-2 > proestrous and oestrous. L-NA shifted the curve to the right in all groups except dioestrous day-1. IBU inhibited the ACh response in the pregnant group only. TBA virtually abolished the response in all groups. These results suggest that in the uterine vascular bed from pregnant rats, EDHF, along with NO and a dilator prostanoid mediate ACh-induced dilatation. In contrast, in the dioestrous day-1 group, only EDHF seems to be released by ACh in this vascular bed. In the oestrous, dioestrous day-2 and proestrous groups, ACh releases both EDHF and NO.

Abnormal proliferative response of the carotid artery of spontaneously hypertensive rats after angioplasty may be related to the depolarized state of its smooth muscle cells.

Hypertension is one of the major precursors of atherosclerotic vascular disease, and vascular smooth muscle abnormal cell replication is a key feature of plaque formation. The present study was conducted to examine the relationship between hypertension and smooth muscle cell proliferation after balloon injury and to correlate neointima formation with resting membrane potential of uninjured smooth muscle cells, since it has been suggested that altered vascular function in hypertension may be related to the resetting of the resting membrane potential in spontaneously hypertensive rats (SHR). Neointima formation was induced by balloon injury to the carotid arteries of SHR and renovascular hypertensive rats (1K-1C), as well as in their normotensive controls, i.e., Wistar Kyoto (WKY) and normal Wistar (NWR) rats. After 14 days the animals were killed and the carotid arteries were submitted to histomorphometric and immunohistochemical analyses. Resting membrane potential measurements showed that uninjured carotid arteries from SHR smooth muscle cells were significantly depolarized (-46.5 +/- 1.9 mV) compared to NWR (-69 +/- 1.4 mV), NWR 1K-1C (-60.8 +/- 1.6 mV), WKY (-67.1 +/- 3.2 mV) and WKY 1K-1C (-56.9 +/- 1.2 mV). The SHR arteries responded to balloon injury with an enhanced neointima formation (neo/media = 3.97 +/- 0.86) when compared to arteries of all the other groups (NWR 0.93 +/- 0.65, NWR 1K-1C 1.24 +/- 0.45, WKY 1.22 +/- 0.32, WKY 1K-1C 1.15 +/- 0.74). Our results indicate that the increased fibroproliferative response observed in SHR is not related to the hypertensive state but could be associated with the resetting of the carotid smooth muscle cell resting membrane potential to a more depolarized state.

Abnormal proliferative response of the carotid artery of spontaneously hypertensive rats after angioplasty may be related to the depolarized state of its smooth muscle cells

Hypertension is one of the major precursors of atherosclerotic vascular disease, and vascular smooth muscle abnormal cell replication is a key feature of plaque formation. The present study was conducted to examine the relationship between hypertension and smooth muscle cell proliferation after balloon injury and to correlate neointima formation with resting membrane potential of uninjured smooth muscle cells, since it has been suggested that altered vascular function in hypertension may be related to the resetting of the resting membrane potential in spontaneously hypertensive rats (SHR). Neointima formation was induced by balloon injury to the carotid arteries of SHR and renovascular hypertensive rats (1K-1C), as well as in their normotensive controls, i.e., Wistar Kyoto (WKY) and normal Wistar (NWR) rats. After 14 days the animals were killed and the carotid arteries were submitted to histomorphometric and immunohistochemical analyses. Resting membrane potential measurements showed that uninjured carotid arteries from SHR smooth muscle cells were significantly depolarized (-46.5 + or - 1.9 mV) compared to NWR (-69 + or - 1.4 mV), NWR 1K-1C (-60.8 + or - 1.6 mV), WKY (-67.1 + or - 3.2 mV) and WKY 1K-1C (-56.9 + or - 1.2 mV). The SHR arteries responded to balloon injury with an enhanced neointima formation (neo/media = 3.97 + or - 0.86) when compared to arteries of all the other groups (NWR 0.93 + or - 0.65, NWR 1K-1C 1.24 + or - 0.45, WKY 1.22 + or - 0.32, WKY 1K-1C 1.15 + or - 0.74). Our results indicate that the increased fibroproliferative response observed in SHR is not related to the hypertensive state but could be associated with the resetting of the carotid smooth muscle cell resting membrane potential to a more depolarized state

Influence of oestrous cycle and pregnancy on the reactivity of the rat mesenteric vascular bed.

In isolated, perfused mesenteric vascular beds from female rats, it was assessed whether the constrictor response to cirazoline, an alpha(1)-adrenergic agonist, or acetylcholine (ACh)-induced relaxation was altered by oestrous cycle or pregnancy and the ability of nitric oxide (NO), prostanoids and endothelium-derived hyperpolarizing factor (EDHF) to modulate these responses. Mesenteries, removed from female rats on each oestrous cycle day and gestation day 16, were perfused with physiological salt solution. Tone was induced with cirazoline (1 micromol/l), and concentration-response curves to ACh generated. Responsiveness to ACh was tested in the presence of N(omega)-nitro-L-arginine (L-NA), ibuprofen (IBU) and tetrabutylammonium (TBA), to inhibit nitric oxide synthase (NOS), cyclo-oxygenase and K(+) channels respectively. Cirazoline-induced tone was smaller in pro-oestrous and pregnant groups, but the increase in tone to L-NA was larger in pregnant compared with oestrous and dioestrous groups. Control responses to ACh were not different, but L-NA attenuated the response in virgin groups only. IBU did not affect the ACh response, but TBA attenuated it in all groups. When TBA was introduced first, ACh-induced dilatation was significantly reduced and not altered by L-NA addition. These results suggest that in the mesenteric vascular bed from cycling and pregnant rats, EDHF is the major mediator of ACh-induced dilatation and NOS may be up-regulated in pregnant and pro-oestrous rats.