Developmental atrazine exposure suppresses immune function in male, but not female Sprague-Dawley rats.
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Each year, 75 million pounds of the broadleaf herbicide atrazine (ATR) are applied to crops in the United States. Despite limited solubility, ATR is common in ground and surface water, making it of regulatory concern. ATR suppresses the immunomodulatory hormones prolactin (PRL) and the thyroid hormones (THs), with developmental exposure to ATR permanently disrupting PRL regulation. We hypothesized that ATR may cause developmental immunotoxicity through its disruption of PRL or THs. To test this hypothesis, pregnant Sprague-Dawley (SD) rats were exposed to 35-mg ATR/kg/d from gestational day (GD) 10 through postnatal day (PND) 23. Separate groups were exposed to bromocryptine (BCR) at 0.2 mg/kg/2x/day to induce hypoprolactinemia or to propylthiouracil (PTU) at 2 mg/kg/day to induce hypothyroidism. After the offspring reached immunologic maturity (at least 7 weeks old), the following immune functions were evaluated: natural killer (NK) cell function; delayed-type hypersensitivity (DTH) responses; phagocytic activity of peritoneal macrophages; and antibody response to sheep erythrocytes (SRBC). ATR decreased the primary antibody and DTH responses in male offspring only. Neither PTU nor BCR caused immunosuppression in any measured variable, although PTU increased phagocytosis by peritoneal macrophages. These results demonstrate that developmental exposure to ATR produced gender-specific changes in immune function in adult rats and suggest that immune changes associated with ATR are not mediated through the suppression of PRL or THs. (+info)
Unilateral ureteroperitoneostomy in the management of hypoproteinemia in nephrotic rats with normal renal function.
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Maintenance of serum albumin levels within normal limits is difficult to achieve in nephrotic children with normal renal functions who are unresponsive to specific treatment. One approach in such children is unilateral nephrectomy with rapid progression to renal failure. Peritoneal membrane is permeable to fluids, electrolytes and proteins, and peritoneal space has been used for total parenteral alimentation. Experimental ureteroperitoneostomy has been reported not to cause any significant side effect. The aim of this study was to evaluate the effects of unilateral ureteroperitoneostomy on serum and urine protein levels in rats with adriamycin-induced nephrosis. Adriamycin nephrosis was induced in 45 male Wistar rats. After two weeks, unilateral nephrectomy (Nx), unilateral ureteroperitoneostomy (Up) and sham operated (Sh) groups, each including 15 rats were formed. Serum creatine (S(Cr)) and albumin (S(alb)), and daily urinary protein excretion (U(pro)) were determined before adriamycin injection (week 0), before operations (week 2) and at the end of 6th week in all rats. In addition, percent change in serum albumin (deltaS(alb)) and urine protein levels (deltaU(pro)) between weeks 0-2, 0-6 and 2-6 were calculated for each group (e.g.; deltaS(alb) 0-2 = [S(alb) week 2-S(alb) week 0]/S(alb) week 0 x 100). Then, these parameters were compared within and between the groups. Furthermore, peritoneal tissue samples were obtained from the rats in Sh and Up groups to be examined for pathological changes. S(Cr) did not change within and in between the groups during the study period. S(alb) decreased significantly at weeks 2 and 6 with respect to week 0 in all three groups. In addition, although S(alb) tended to decrease at week 6 with respect to week 2 in all groups, this was significant only in Sh group. U(pro) increased significantly at weeks 2 and 6 with respect to week 0, and at week 6 with respect to week 2 in all groups. However, S(alb) and U(pro) were not different between the three groups at weeks 0.2 and 6. On the other hand, deltaS(alb) and deltaU(pro) were not different between Sh vs. Nx and Nx vs. Up rats, but deltaS(alb) 0-6, deltaS(alb) 2-6 and deltaU(pro) 0-6 were significantly lower in Up group compared to Sh group. Histopathological examination of peritoneal samples revealed significantly higher fibrosis score in Up group compared to Sh group. In conclusion, unilateral ureteroperitoneostomy may one important therapeutic selection in the treatment of intractable nephrotic syndrome. However, peritoneal fibrosis could be a concern for further use of peritoneum in case of end stage renal failure. (+info)
Measurements of serum free cortisol in critically ill patients.
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BACKGROUND: Because more than 90 percent of circulating cortisol in human serum is protein-bound, changes in the binding proteins can alter measured serum total cortisol concentrations without influencing free concentrations of this hormone. We investigated the effect of decreased amounts of cortisol-binding proteins on serum total and free cortisol concentrations during critical illness, when glucocorticoid secretion is maximally stimulated. METHODS: Base-line serum total cortisol, cosyntropin-stimulated serum total cortisol, aldosterone, and free cortisol concentrations were measured in 66 critically ill patients and 33 healthy volunteers in groups that were similar with regard to sex and age. Of the 66 patients, 36 had hypoproteinemia (albumin concentration, 2.5 g per deciliter or less), and 30 had near-normal serum albumin concentrations (above 2.5 g per deciliter). RESULTS: Base-line and cosyntropin-stimulated serum total cortisol concentrations were lower in the patients with hypoproteinemia than in those with near-normal serum albumin concentrations (P<0.001). However, the mean (+/-SD) base-line serum free cortisol concentrations were similar in the two groups of patients (5.1+/-4.1 and 5.2+/-3.5 microg per deciliter [140.7+/-113.1 and 143.5+/-96.6 nmol per liter]) and were several times higher than the values in controls (0.6+/-0.3 microg per deciliter [16.6+/-8.3 nmol per liter], P<0.001 for both comparisons). Cosyntropin-stimulated serum total cortisol concentrations were subnormal (18.5 microg per deciliter [510.4 nmol per liter] or less) in 14 of the patients, all of whom had hypoproteinemia. In all 66 patients, including these 14 who had hypoproteinemia, the base-line and cosyntropin-stimulated serum free cortisol concentrations were high-normal or elevated. CONCLUSIONS: During critical illness, glucocorticoid secretion markedly increases, but the increase is not discernible when only the serum total cortisol concentration is measured. In this study, nearly 40 percent of critically ill patients with hypoproteinemia had subnormal serum total cortisol concentrations, even though their adrenal function was normal. Measuring serum free cortisol concentrations in critically ill patients with hypoproteinemia may help prevent the unnecessary use of glucocorticoid therapy. (+info)
A patient with protein-losing enteropathy associated with systemic lupus erythematosus.
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A 46-year-old woman previously diagnosed as having systemic lupus erythematosus presented with severe hypoalbuminemia and anasarca. She was demonstrated to have protein-losing enteropathy without any other active symptoms of SLE. Her bowel habit was normal and endoscopic examination revealed non-specific colitis and a small ulcer in the duodenum. Serum biochemistry showed an abnormal profile of the serum protein, including severe hyperlipoproteinemia and hyperfibrinogenemia. The process of protein-losing was not selective in terms of the molecular size. All of these symptoms and the abnormalities in laboratory data were improved by corticosteroid therapy. (+info)
Familial hypercatabolic hypoproteinemia caused by deficiency of the neonatal Fc receptor, FcRn, due to a mutant beta2-microglobulin gene.
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Two siblings, products of a consanguineous marriage, were markedly deficient in both albumin and IgG because of rapid degradation of these proteins, suggesting a lack of the neonatal Fc receptor, FcRn. FcRn is a heterodimeric receptor composed of a nonclassical MHC class I alpha-chain and beta(2)-microglobulin (beta(2)m) that binds two ligands, IgG and albumin, and extends the catabolic half-lives of both. Eight relatives of the siblings were moderately IgG-deficient. From sera archived for 35 years, we sequenced the two siblings' genes for the heterodimeric FcRn. We found that, although the alpha-chain gene sequences of the siblings were normal, the beta(2)m genes contained a single nucleotide transversion that would mutate a conserved alanine to proline at the midpoint of the signal sequence. Concentrations of soluble beta(2)m and HLA in the siblings' sera were <1% of normal. Transfection assays of beta(2)m-deficient cultured cells with beta(2)m cDNA indicated that the mutant beta(2)m supported <20% of normal expression of beta(2)m, MHC class I, and FcRn proteins. We concluded that a beta(2)m gene mutation underlies the hypercatabolism and reduced serum levels of albumin and IgG in the two siblings with familial hypercatabolic hypoproteinemia. This experiment of nature affirms our hypothesis that FcRn binds IgG and albumin, salvages both from a degradative fate, and maintains their physiologic concentrations. (+info)
Familial yellow nail syndrome.
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A 70-year-old woman with yellow nail syndrome and right-sided pleural effusion, lower extremity edema, and hypoalbuminemia was followed for 18 months. She reported an 8-year history of asthma. She had four children (3 boys and 1 girl). Dystrophy, changes in color and shape of nails both hands and foot, along with lower extremity edema was observed in the daughter and two of her sons. One son had asthma. The patient reported that her grandmother had similar nail abnormality and lower extremity edema. Other family members and patient's grandchildren were healthy. This report demonstrates a case of familial yellow-nail syndrome. (+info)
A reappraisal of the criteria to diagnose plasma leakage in dengue hemorrhagic fever.
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A study was undertaken to analyze the usefulness of radiographic and ultrasonographic findings and area specific hematocrit cut off values in Dengue Hemorrhagic Fever (DHF). Of the 65 cases, 35 were DHF and 30 were Dengue Fever as per the WHO case definition. Among the DHF cases, hemoconcentration (>20%) was detected in 20 cases (57.14%), hypoproteinemia in 11 (31.42%) and clinical evidence of pleural effusion and or ascites in 25 (71.42%). Hemoconcentration based on area specific hematocrit cut off values was observed in 32 cases (91.42%). Ultrasonographic evidence of plasma leakage was seen in 32 cases (91.42%). In detecting plasma leakage, area specific hematocrit cut off values and ultrasonography had the highest sensitivity (91.42%), while ultrasonography had the highest negative predictive value of 84.21%. Clinical evidence of plasma leakage was more frequent than hemoconcentration or hypoproteinuria. Ultrasonography is an ideal non-invasive investigation to detect plasma leakage and area specific hematocrit values are useful as evidence of plasma leakage. (+info)
Disappearance of diabetic macular hard exudates after hemodialysis introduction.
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We report herein the disappearance of macular hard exudates after the introduction of hemodialysis in diabetic patients. A 62-year-old woman and a 52-year-old man with diabetes mellitus showed hard exudates in the macula of the left eyes. Both patients had previously undergone panretinal photocoagulation in both eyes. During the follow-up, hemodialysis was introduced for deteriorating chronic renal failure caused by diabetic nephropathy. Half a year later, macular hard exudates in the left eyes disappeared dramatically in both patients, but the visual acuity remained the same. No additional laser treatment was done during the observation period. Hemodialysis is considered to have accelerated the resolution of macular hard exudates in both patients. The deposition of macular hard exudates in diabetic patients is due in part to concurrent poor renal function. (+info)