Interaction between prostaglandin E2 and leukotriene D4 on the excretion of electrolytes by the dog kidney in vivo

Recent experiments indicate that prostaglandin E2 potentiates the vasodilatory properties of leukotrienes in the skin microcirculation. The present experiments were undertaken to study the effect of leukotriene D4 and prostaglandin E2 on renal hemodynamics and urinary electrolytes in the dog. Experiments were performed in three groups of anesthetized Mongrel dogs: the first group was studied under hydropenia, whereas the two remaining groups were studied during water diuresis with (Group 3) or without indomethacin (Group 2). LTD4 (100 ng/min) and PGE2 (3 ug/min) were infused in the left renal artery to minimize systemic effects of these compounds. LTD4 alone failed to influence urinary sodium excretion in all 3 groups. In Group 1, urinary sodium increased from 77 +/- 6 to 393 +/- 74 uEq/min during PGE2, and further increased to 511 +/- 52 uEq/min during LTD4 + PGE2. No change occurred in the contralateral right kidney. In this group, glomerular filtration as well as renal plasma flow were not statistically influenced. In Group 2, the same phenomenon was observed for urinary sodium. The combined infusion of LTD4 + PGE2 increased urinary sodium without significant changes in glomerular filtration and renal plasma flow. Finally, in Group 3, indomethacin was shown to reduce the natriuretic effects of LTD4 and PGE2: during PGE2 alone, urinary sodium increased from 90 +/- 14 to 260 +/- 66 uEq/min, and only rose from 80 +/- 10 to 175 +/- 19 uEq/min during the combined infusion of LTD4 and PGE2. In groups 2 and 3, free water clearance was utilized as an index of sodium chloride reabsorption in the thick ascending limb: this parameter increased from 2.35 +/- 0.25 to 4.70 +/- 0.30 ml/min, while urinary volume was increasing from 3.55 +/- 0.25 to 10.05 +/- 0.65 ml/min, during LTD4 + PGE2. Indomethacin, administered in Group 3, (3 mg/kg/hr) again abolished the effect of combined PGE2 + LTD4. These results indicate a potentiating effect of leukotriene D4 on the PGE2-induced natriuresis in the anesthetized dog. These phenomena occurred in the absence of significant changes in renal hemodynamics, therefore suggesting a direct tubular effect of these arachidonic acid metabolites. Finally, the water diuresis experiments suggest a proximal site of action of PGE2 and LTD4.     

Inhibition by serum of autoimmune aspermatogenic orchitis.

Inhibition by serum of experimental autoimmune orchitis (EAO) was studied in guinea-pigs. It was found that the capacity of an autoantigen, antigen P, purified from guinea-pigs' spermatozoa, to produce lesions of EAO could be inhibited by mixing antigen P with a small amount of normal human serum before injection into guinea-pigs. In protected animals, cell-mediated immunity and humoral antibodies to antigen P were also significantly suppressed.     

Histology of tooth attachment tissues and plicidentine in Varanus (Reptilia: Squamata), and a discussion of the evolution of amniote tooth attachment

Few recent studies have examined the histological basis for tooth attachment in squamates. In the past few years, a surge of interest in this topic has led to the intriguing suggestion that the major tissues derived from the tooth germ (enamel, dentine, cementum and alveolar bone), are conservative and are present in all amniotes. In this study, we describe the histology and development of the tooth attachment complex in Varanus rudicollis, the rough‐neck monitor. We provide the first published evidence for the role of cementum and alveolar bone in tooth attachment in varanoid lizards. In Varanus, cementum is deposited on the external surface of the tooth root as well as at the base of the tooth, where it plays a role in the attachment of the tooth to the jawbone. Alveolar bone is also involved in tooth ankylosis. Our results support the hypothesis that the major tooth germ tissues are found in all amniotes. We provide insights into the structure and development of plicidentine, defined as infolding of the dentine around the tooth base. This feature is unique to varanoids among extant tetrapods and is the third tissue implicated in tooth attachment in Varanus. Plicidentine develops asymmetrically along the labial‐lingual axis of a tooth. Varanus is characterized by the presence of both primary and higher‐order lamellae, which anastomose to form a honeycomb‐like surface that then interacts with the more basal attachment tissues. J. Morphol. 2011. © 2011 Wiley‐Liss, Inc.     

Hemochromatosis in Two Female Olive Baboons (Papio anubis)

This report describes hemochromatosis associated with chronic parenteral iron dextran administration in 2 female olive baboons (Papio anubis). These baboons were enrolled on an experimental protocol that induced and maintained anemia by periodic phlebotomy for use in studying potential treatments for sickle cell anemia. The 2 baboons both presented with clinical signs consistent with iron overload, including decreased appetite, weight loss, elevated liver enzymes, and hepatosplenomegaly. Histopathologic findings supported a morphologic diagnosis of systemic hemosiderosis, as evidenced by the overwhelming presence of iron in the reticuloendothelial system and liver after the application of Prussian blue stain. This finding, combined with the clinical presentation, lead to a final diagnosis of hemochromatosis. This case report suggests that providing anemic patients with chronic parenteral iron supplementation in the absence of iron deficiency can result in iatrogenic iron overload and subsequent systemic toxicity. Furthermore, these subjects may present with hemochromatosis and its associated clinical signs many years after cessation of iron supplementation.

Iron is an essential micronutrient that plays an important role in cellular proliferation, oxygen transport, and cellular energy generation.^13,26,31 The highest levels of iron in the body is found in the erythrocytes, followed by the liver, reticuloendothelial system, and skeletal muscle.⁹ Three main mechanisms regulate iron: 1) dietary absorption through the proximal duodenum; 2) recycling of senescent red blood cells by macrophages; and 3) storage in the liver. The liver produces the hormone hepcidin, which is the primary negative regulator of systemic iron metabolism.³⁸ Hepcidin controls the release of iron from enterocytes and macrophages into the circulation by binding to and degrading ferroportin, the only mammalian iron exporter.³⁵ When plasma iron levels are high, hepatocytes increase hepcidin synthesis. The increased hepcidin subsequently suppresses gastrointestinal absorption of exogenous iron and iron release from macrophages into circulation.³¹Approximately 1 to 2 mg of iron is lost per day through enterocyte and skin sloughing.³⁸ Iron can also be lost by hemorrhage, menstruation, and parasitic infestation.³⁸ Other than these, the body has no active mechanism for iron excretion. Iron overload can result from acute iron toxicity or chronic accumulation of iron over time.³⁵ Iron is primarily stored in the liver in the form of ferritin, and excess iron is transformed into hemosiderin, an oxidized form of ferritin. Hemosiderin is an iron-containing pigment found primarily in macrophages and hepatocytes.³⁵Hemosiderosis occurs when iron accumulates in tissues, but causes no subsequent organ injury or dysfunction. It is not typically pathologic and can be reversed.⁹ In contrast, hemochromatosis occurs when iron accumulation results in organ injury and dysfunction.³⁵ The 2 types of hemochromatosis are primary and secondary. Primary hemochromatosis, also known as hereditary hemochromatosis, is the result of inherited mutations in genes that are important for iron homeostasis. The most common gene involved in primary hemochromatosis is HFE, an autosomal recessive trait.¹¹ Almost all forms of primary hemochromatosis involve low levels of hepcidin expression.¹¹ Secondary hemochromatosis can occur due to iron-loading anemias such as thalassemia and sideroblastic anemia, chronic liver disease (for example, hepatitis C), and iatrogenic causes, such as excess iron in the diet or parenteral administration.¹⁶ Hemolytic anemia and repeated blood transfusions can also result in secondary hemochromatosis.³⁵ In primary hemochromatosis, iron typically accumulates in the liver, pancreas, heart, and endocrine glands for many years.^16,24 In contrast, secondary hemochromatosis patients often accumulate iron in the reticuloendothelial system, bone marrow, and lymph nodes¹⁶ over a shorter time period,²⁴ with excess iron accumulating in the hepatocytes after the reticuloendothelial system has become saturated with iron.¹⁶ Symptoms of iron overload can vary among individuals due to the number of organ systems affected. These symptoms may include lethargy, arthralgia, skin hyperpigmentation, abdominal pain, abnormal liver chemistry tests, and hepatomegaly.¹⁵ In the current report, we describe 2 cases of hemochromatosis in female baboons after chronic parenteral administration of iron dextran as part of an anemia maintenance protocol used to study sickle cell anemia treatments.     

Influence of young black spruce plantations on moose winter distribution

Logging in the boreal forest may benefit moose by increasing food availability. However, the influence of tree plantations on moose behavior, especially on moose spatial ecology, is poorly understood. We assessed the impacts of black spruce plantations on moose winter distribution at a landscape scale in the Bas-Saint-Laurent region (Québec, Canada). We used winter aerial surveys to examine relationships among plantation characteristics and other habitat variables known to affect moose distribution. The total area of plantations positively influenced moose abundance, but highly aggregated plantations resulted in fewer moose. Moose abundance was also positively associated with food availability and the density of edges between stands providing cover and stands offering high food availability, but moose abundance was negatively associated with road density. Although plantation characteristics were less influential than habitat variables related to foraging and predator avoidance, we demonstrate that the area of black spruce plantations and their configuration should be considered in moose management. We conclude that an integrated management strategy is needed to find a balance between overdeveloped road networks (needed to join homogeneously distributed plantations) and agglomerated plantations in order to mitigate impacts on moose winter distribution. © 2012 The Wildlife Society.     

The identification of disease-induced biomarkers in the urine of BSE infected cattle

Background  

The bovine spongiform encephalopathy (BSE) epidemic and the emergence of a new human variant of Creutzfeldt-Jakob Disease (vCJD) have led to profound changes in the production and trade of agricultural goods. The rapid tests currently approved for BSE monitoring in slaughtered cattle are all based on the detection of the disease related isoform of the prion protein, PrP^d, in brain tissue and consequently are only suitable for post-mortem diagnosis. Objectives: In instances such as assessing the health of breeding stock for export purposes where post-mortem testing is not an option, there is a demand for an ante-mortem test based on a matrix or body fluid that would permit easy access and repeated sampling. Urine and urine based analyses would meet these requirements.     

Factors influencing the in vitro growth of Mycobacterium leprae: effect of oxygen.

In our efforts to evaluate factors responsible for in vitro growth of Mycobacterium leprae in DH medium and also to improve the system, effects of oxygen tension on in vitro growth of M. leprae were determined. This was achieved by varying the ratio between DH medium and free air space above the medium in the culture tubes. Growth-competent M. phlei (ATCC 11758) could tolerate all the oxygen it can get in the medium. On the other hand, M. leprae seemed to be of microaerophilic nature. In vivo-grown M. leprae cells were more sensitive than their counterparts that were adapted to in vitro environment. In vivo-grown cells grew better when 70% of the space in culture tube was occupied by DH medium. These in vitro-adapted cells gave optimum growth in subcultures when the air spaces in the culture tubes were 40-50%. The role of oxygen tensions in the development of lesions in leprosy patients and armadillos has been discussed.