Tissue Balance Research Articles

Endogenous MCP-1 Influences Systemic Cytokine Balance in a Murine Model of Acute Septic Peritonitis

Sepsis and septic syndrome represent an intense systemic response with multiple physiologic and immunologic abnormalities, leading to multiple organ failure. Recent investigations suggest that the critical conditions are balanced by endogenous cytokines. In the present study, we examined the involvement of endogenous monocyte chemoattractant protein (MCP)-1 in the regulation of cytokine production in tissue/organs in a murine model of acute septic peritonitis induced by cecal ligation and puncture (CLP). Initial studies showed that CLP induced elevated levels of MCP-1 in tissues, such as liver, lung, and kidney. To neutralize endogenous MCP-1, either anti-MCP-1 antibodies or control antibodies were intraperitoneally administered 2 h prior to CLP. Administration of anti-MCP-1 antibodies resulted in a decrease in the level of interleukin (IL)-13 in tissues, while increasing the level of tumor necrosis factor-α, compared to control. In addition, anti-MCP-1 treatment decreased the level of IL-12 and, in contrast, increased the level of IL-10 in specific tissues. These findings suggest that endoge nous MCP-1 influences the cytokine balance in tissues in favor of anti-inflammatory and immune-enhancing cytokines, probably protecting the host from tissue/organ damage during sepsis.

Effects of castration and androgen replacement on erectile function in a rabbit model.

We investigated, in a rabbit model, the effects of castration and testosterone replacement on: 1) the hemodynamics of the corpus cavernosum; 2) alpha-1 adrenergic receptor protein expression; 3) neural NO synthase protein expression and activity; 4) phosphodiesterase type 5 activity; and 5) trabecular smooth muscle/connective tissue balance. One week after bilateral orchiectomy, animals were treated for 7 days with vehicle alone, testosterone, or estradiol. Intact control animals received vehicle only. Systemic arterial blood and intracavernosal pressures (ICP) were measured in each animal before and after electrical stimulation of the cavernosal nerve. Alpha1-adrenergic receptor protein expression was determined by ligand binding studies. NO synthase expression and activity were determined by Western blot analyses and conversion of L-arginine to citrulline, respectively. Phosphodiesterase type 5 activity was determined by hydrolysis of guanosine 3',5'-cyclic monophosphate (cGMP) in tissue extracts in the absence or presence of 100 nM sildenafil. Smooth muscle content was assessed by Masson's trichrome staining and computer-assisted histomorphometry. Castration significantly reduced ICP, but it did not alter systemic arterial blood pressure during stimulation of the cavernosal nerve. Testosterone, but not estradiol, treatment prevented the effects of castration and restored ICP to values similar to those obtained in intact animals. Castration reduced expression of alpha1-adrenergic receptor, and this reduction was prevented or reversed by testosterone replacement. Neural NO synthase protein expression and total activity were not altered significantly by castration or after testosterone replacement. However, phosphodiesterase type 5 activity increased in castrated animals treated with testosterone. Castration significantly reduced trabecular smooth muscle content, and this reduction was restored by testosterone (but not estradiol) treatment. The results of this study demonstrate that androgen deprivation alters the functional responses and structure of erectile tissue.

Effects of N-acetylcysteine and 2,3-dimercaptosuccinic acid on lead induced oxidative stress in rat lenses

Lead (Pb) is known to disrupt the pro-oxidant/anti-oxidant balance of tissues which leads to biochemical and physiological dysfunction. The present study investigated the effects of exposure on the redox status of the lenses of Fisher 344 rats and examined whether antioxidant or chelator administration reversed these changes. Animals were given 5 weeks of 2000 ppm Pb exposure followed by 1 week of either antioxidant, chelator or distilled water administration. Glutathione (GSH) and cysteine (CYS) levels decreased in the Pb-exposed group. N-acetylcysteine or 2,3-dimercaptopsuccinic acid (Succimer) supplementation following Pb intoxication resulted in increases in the GSH and CYS levels. Protein bound glutathione (PSSG) and cysteine (PSSC) increased following Pb exposure. In the Succimer-treated animals, the PSSG decreased significantly. The glutathione disulfide (GSSG) levels remained unchanged. Malondialdehyde (MDA) levels, a major lipid peroxidation byproduct, increased following Pb exposure and decreased following Succimer treatment. Our results suggest that antioxidant supplementation, as well as chelation, following Pb exposure may enhance the reductive status of lenses.

Immunolocalization of collagenase (MMP-1) and stromelysin (MMP-3) in the gingival tissues of organ transplant patients medicated with cyclosporin.

Cyclosporin-induced gingival overgrowth results from a disturbance in the homeostatic balance in the gingival tissues which is characterised by both an increase in the number of fibroblasts and in the volume of the extracellular matrix. Whilst the accumulation of the collagenous matrix is well recognised, little attention has been paid to the role of the degradative enzymes in the development of this condition in vivo. The matrix metalloproteinases MMP-1 (collagenase) and MMP-3 (stromelysin) were immunolocalized using specific polyclonal and monoclonal antisera in gingival specimens from 18 patients with drug-induced gingival overgrowth and 6 control subjects. A positive granular pattern of MMP-1 staining was seen in the vast majority of fibroblasts in specimens from drug-free controls throughout the connective tissue. This was in marked contrast to the findings in overgrown tissue, where positive cytoplasmic staining was shown by only a small number of fibroblasts. Where fibroblast staining occurred in overgrown tissue, the intracellular pattern was the same as in the drug free tissue. Positive staining was, however, largely confined to a small number of fibroblasts in the lamina propria of the outer gingival mucosa and even in this region there were areas that showed little or no fibroblast staining. This apparent cessation of collagenase production by many of the fibroblasts in gingival overgrowth supports the hypothesis that perturbation of collagenase activity is responsible for the disturbance in the homeostatic balance, which is pivotal to this condition.

Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the Society for the Study of Impotence.

During erection, oxygen tension changes in the corpus cavernosum penis from 25-40 mm Hg in the flaccid state to 90-100 mm Hg in the erect state. The relationship between corpus cavernosum trabecular structure and erectile function is dependent on a critical balance of smooth muscle to connective tissue for successful veno-occlusion. In this article, the potential role for transforming growth factor beta(1) (TGF-beta(1)) and prostaglandin E (PGE) in maintaining a functional smooth muscle/connective tissue balance are discussed as well as the importance of oxygen tension in the synthesis of these factors. Correlations between animal models of disease as well as clinical reports are presented in support of a role for hypoxemia in penile fibrosis. A case is presented for a biological basis of nocturnal penile tumescence in the preservation of potency and an overall hypothesis for the molecular pathology of erectile dysfunction is proposed.

Effect of dehydroepiandrosterone on brown adipose tissue and energy balance in mice.

In order to investigate the reported antiobesity action of dehydroepiandrosterone (DHEA), a complete energy balance was made on four groups of mice. Group A was fed the standard Purina diet, group B the same diet to which DHEA was added (0.3%), group C the Purina diet supplemented with palatable high fat food (meat spread), and group D the same diet as group C, to which DHEA was added. Food intake which was larger in groups C and D, was not altered by DHEA treatment. Body weight gain which was comparable for groups A and C, was significantly reduced in the two groups receiving DHEA. The resulting reduced food efficiency caused by DHEA was completely explained by body fat utilization. It was also found that the weight and the protein content of the interscapular brown adipose tissue (BAT) were increased by DHEA treatment suggesting, because of the great thermogenic capacity of this tissue in mice, that it may have been involved in causing the observed reduction in food efficiency. It is also proposed that the action of DHEA may be related to the activation of other tissues such as the liver and muscles. Further investigations are needed to verify this possibility.

Biochemical mechanisms for disrupting the proteinase-proteinase inhibitor balance in tissues.

The regulation of proteolytic activity in tissues by members of the Serpin family of inhibitors is normally tightly controlled. However, numerous mechanisms are available for interrupting this process in pathological tissues by depleting functional inhibitory activity at inflammatory foci. These include a) saturation of inhibitory activity due to excessive proteinase release from inflammatory cells, b) oxidative inactivation of inhibitory activity, c) proteolytic inactivation of inhibitory activity by non-complexing proteinases. In an attempt to regain a normal inhibitor-proteinase balance, however, it is now known that both inhibitor: enzyme complexes and inactive forms of inhibitors can act as signalling agents for the resynthesis of functionally active proteins. Thus, during inflammatory episodes where the levels of functional inhibitors are continually being depleted, mechanisms are in place to signal either directly or indirectly for their resynthesis.

Iron Deficiency Stress Response of Epipremnum aureum and Philodendron scandens Subspecies Oxycardium

Summary Philodendron [ Philodendron scandens Koch, C. and H. Sello subspecies oxycardium (Schott) Bunt.] grown in Hoagland Solution Number 1, with all N supplied as nitrate, lowered solution pH from 5.1 to below 3 when the solution contained no Fe, 0.1 mM FeEDTA, or 6.3 mM Fe 2 O 3 . Philodendron with no Fe became severely chlorotic, while plants with Fe 2 O 3 or FeEDTA remained green. Reductant levels in the philodendron solutions did not differ regardless of Fe treatment. Pothos [ Epipremnum aureum (Linden and Andre) Bunt.] caused the solution pH to rise above 7 with FeEDTA, but the pH dropped with no Fe and at least initially with Fe 2 O 3 . With no Fe, pothos became severely chlorotic. With Fe 2 O 3 , pothos became slightly chlorotic but regreened as the pH dropped. After regreening of plants, the solution pH increased to above 7. Solutions of chlorotic pothos plants had reductant concentrations 10 to 25 times as high as those of Fe-sufficient plants. A macronutrient charge balance of leaf tissue indicated excess anion uptake only for the pothos receiving FeEDTA, which was consistent with the rise in nutrient solution pH. All other pothos and all philodendron treatments had excess cation uptake, which was consistent with the drop in nutrient solution pH in these treatments. Pothos had a strong Strategy I Fe-deficiency stress response, i.e. pH decrease and production of Fe reductant. Philodendron had some aspects of a Strategy I Fe-deficiency stress response but was unique because it lowered the pH of an all nitrate-N solution, regardless of Fe availability or plant Fe status.

Feed Efficiency: A Composite Trait of Dairy Cattle

A pleiotropic pathway of correlated response of feed efficiency from selection for milk yield has been inferred from a large genetic correlation coefficient. However, in studies to estimate the genetic correlation, cows were fed according to yield (i.e., not ad libitum), and there was no accounting for body tissue balance (i.e., catabolism or repletion status). Research evidence indicates that the apparent feed efficiency of dairy cattle is a composite trait of physiological processes that does not include genetic covariance between yield and rate (efficiency) of converting dietary nutrients directly into milk. Absence of pleiotropy in direct nutrient utilization makes feed efficiency an artifact of the selection response in milk, which depends on the genotypes and within-animal environments for milk yield, tissue balance, and appetite. Several reports point to a major connection between genetic ability in milk and tissue balance.

Isolation and properties of oxidized alpha-1-proteinase inhibitor from human rheumatoid synovial fluid

Human alpha-1-proteinase inhibitor (α-1-PI) from synovial fluid has been isolated to near 90% purity. The preparation has a molecular weight near 52,000, contains 3.5 residues of methionine sulfoxide, and an amino terminal glutamine residue. Sequence studies indicate that the first 17 residues, normally present in plasma α-1-PI, are missing from this protein. The inhibitor did not form a complex with porcine pancreatic elastase but, instead, was converted to a lower molecular weight form. Sequence studies on the latter indicated that two methionyl residues, one at the P 1 reactive site and the other at P 8, had been oxidized. These data confirm the fact that oxidized α-1-PI may be formed in vivo , presumably by the action of myeloperoxidase. This latter effect may alter the proteinase-proteinase inhibitor balance in tissues so that excess proteolysis and abnormal tissue degradation may occur.

Zinc Response in Corn as Influenced by Genetic Variability1

AbstractInfluence of genetic variability on Zn response in recently improved corn (Zea mays L.) genotypes has not been investigated. Therefore, eight genotypes representing indigenous, hybrid, and composite varieties, were evaluated in the greenhouse using a Zn deficient loamy sand soil (Typic Torripsamments) at 0 (original soil), 5, and 10 ppm Zn applied to the soil. Zinc deficiency symptoms, dry matter yield response (6 weeks after sowing), Zn concentration, and P/Zn and Fe/Zn ratios were the criteria for evaluation. There was considerable variation among the eight genotypes in the severity of Zn deficiency symptoms, growth depression, Zn concentration, P/Zn, and Fe/Zn ratios under Zn stress conditions. The depression in shoot and root dry matter yield under Zn stress conditions ranged from 78 to 95 and 72 to 94%, respectively, as compared to 5 ppm supplemental Zn level. Zinc concentration in different genotypes under Zn stress condition varied from 7.4 to 20.5 ppm. The differential response among the genotypes was found to be associated with their capability to exploit soil Zn and/or translocate it to the shoot. The contribution of P/Zn and/or Fe/Zn balance in tissues to the variability in Zn responses was not significant.

Cyclophosphamide (endoxan) metabolism in the rabbit: metabolic balance and elimination kinetics in different tissues and organs following oral administration.

Cyclophosphamide (endoxan) metabolism in the rabbit: metabolic balance and elimination kinetics in different tissues and organs following oral administration.

Influence of catecholamines on development of myocardial neurodystrophies.

Myocardial dystrophy in rats and rabbits was produced by electric irritation either of the aortic arch or hypothalamus. It was found that 2–3 h after beginning the stimulation the noradrenalin content in myocardium showed a sharp decrease. A similar decrease in noradrenalin is produced by the injection of toxic doses of exogenous noradrenalin and isoproterenol. Postsynaptic adrenolytics do not prevent exhaustion of catecholamines but do prevent neurogenous dystrophies. An adrenergic blocker, bretylium, and a precursor of noradrenalin, DOPA, prevent exhaustion and also partly protect from neurodystrophies. A conclusion is made of the significant role of the disturbance of catecholamine balance in tissues in the development of neurogenous dystrophies.

Seasonal and diurnal changes in water balance of fruits, cones, and leaves of forest trees

Seasonal variations in actual moisture content (MC), moisture content as percent of dry weight (% MC), and dry weight were determined for fruits of Acer rubrum L., Quercus rubra L., and Prunus serotina Ehrb. at weekly or 2-weekly intervals. On selected dates diurnal variations in MC, % MC, and dry weight of fruits or cones and leaves of Quercus rubra, Prunus serotina, P. virginiana L., and Pinus banksiana Lamb. were determined at 4-hour intervals during the day and night. Percentage moisture content of reproductive tissues and leaves was variously influenced by water uptake or loss, change in dry weight, or both of these. The water balance of different tissues of the same organ varied differently, both seasonally and diurnally, in the same species as well as between species. Percentage moisture content alone is not an accurate indicator of internal water balance of plants and should be interpreted in relation to both water weight and dry weight changes of tissues.

Estimation of rapidly exchangeable cellular thyroxine from the plasma disappearance curves of simultaneously administered thyroxine-131-I and albumin-125-I.

A mathematical analysis of the plasma disappearance curves of simultaneously injected thyroxine-(131)I and albumin-(125)I allows the development of simple formulas for estimating the pool size and transfer kinetics of rapidly exchangeable intracellular thyroxine in man. Evidence is presented that the early distribution kinetics of albumin-(125)I can be used to represent the expansion of the thyroxine-(131)I-plasma protein complex into the extracellular compartment. Calculations indicate that approximately 37% of total body extrathyroidal thyroxine is within such exchangeable tissue stores. The average cellular clearance of thyroxine is 42.7 ml per minute, a value far in excess of the metabolic clearance of this hormone. Results of external measurements over the hepatic area and studies involving hepatic biopsies indicate that the liver is an important but probably not the exclusive component of the intracellular compartment. The partition of thyroxine between cellular and extracellular compartments is determined by the balance of tissue and plasma protein binding factors. The fractional transfer constants are inversely related to the strength of binding of each compartment and directly proportional to the permeability characteristic of the hypothetical membrane separating compartments. Appropriate numerical values for these factors are assigned. An increased fractional entrance of thyroxine-(131)I into the cellular compartment was noted in a patient with congenital decrease in the maximal binding capacity of thyroxine-binding globulin and in three patients after the infusion of 5,5-diphenylhydantoin. Decreased intracellular space and impaired permeability characteristics were observed in five patients with hepatic disease. Studies of the rate of entrance of thyroxine-(131)I and albumin-(125)I into the pleural effusion of a patient with congestive heart failure suggested that transcapillary passage of thyroxine independent of its binding protein is not a predominant factor in the total distribution kinetics of thyroxine-(131)I. The thesis is advanced that the distribution of thyroxine, both within the extracellular compartment and between the extracellular and intracellular compartments, is accomplished largely by the carrier protein and the direct transfer of thyroxine from one binding site to another. The concept of free thyroxine is reassessed in terms of this formulation.

The effect of ion exchange resins in the paroxysmal disorders of the nervous system.

Paroxysmal disorders of the nervous system such as epilepsy, migraine, and Meniere's disease can develop a disturbance of electrolyte and water balance of cerebral and labyrinthine tissues when the paroxysms of the attack become frequent and severe. Experimental work and tissue analysis support this assumption. The introduction of ion exchange resins into the field of therapy has offered an opportunity to influence electrolyte (particularly Na and K) and water balance in these conditions. Clinical experience and results from the use of these resins have established their usefulness in the therapy of epilepsy, migraine, and Meniere's disease.