High protein diet attenuates histopathologic organ damage and vascular leakage in transgenic murine model of sickle cell anemia.

Previous reports have shown that a high protein diet improves weight gain and decreases expression of inflammatory markers in weanling Berkeley transgenic sickle cell mice. The effect of this diet on the underlying histopathology, however, has not been studied. Age-matched, male C57BL/6 controls (n = 24), Berkley sickle mice (n = 31) and Townes sickle mice (n = 14) were randomized in a terminal experiment at weaning to isoenergetic diets, with either normal (20%) or high (35%) amount of energy from protein, by replacing dextrin. Tissue sampling for blinded histologic study and scoring of changes at baseline and after 3 months of feedings showed progressive siderosis and infarcts in spleen, kidney, and liver in all sickle groups, and no significant changes in age- and sex-matched normal controls. High-protein (35%) fed Berkeley sickle mice had significantly fewer (p < 0.01) infarcts in spleen (35.7% less), liver (12.5% less), and kidney (28.6% less) and lower histopathologic scores (p < 0.01) for chronic tissue injury in liver and spleen than matched normal-protein (20%) fed Berkeley sickle mice. In addition, high-protein fed Townes sickle mice had less vascular leakage (∼36%) in the heart, lungs, and brain and a better survival rate (21%) than matched normal-protein Townes sickle mice. This is the first report of histopathologic evidence that a high protein:calorie diet attenuates sickle cell related chronic organ injury in transgenic sickle cell mouse models.

Histomorphologic assessment of formalin substitute fixatives for diagnostic surgical pathology.

CONTEXT: In 1987, the Formaldehyde Standard became law in the United States, alerting laboratory workers to the potential carcinogenicity of formaldehyde. As a result, a variety of proprietary fixatives were developed for use in surgical pathology. OBJECTIVE: To assess histomorphology with different formalin substitute fixatives. DESIGN: Four experienced board-certified surgical pathologists examined 7 specimens (hepatocellular carcinoma, ovarian sex cord/stromal tumor, myxoid liposarcoma, uterine endometrioid adenocarcinoma, splenic follicular hyperplasia, infiltrating mammary carcinoma, and cecal signet ring carcinoma) fixed with formalin and 5 proprietary fixatives advertised as formalin replacements. In a blind study, the pathologists rated cellular outlines, cytoplasmic detail, nuclear detail, erythrocyte integrity, lymphocyte integrity, overall morphology, and overall staining in each case. RESULTS: Formalin received the highest overall morphology and staining scores, followed by Glyo-Fixx, STF-Streck, Omnifix, Histochoice, and Histofix. Formalin also received the highest scores in cellular outline and erythrocyte integrity. Individually, some fixatives performed better in different areas than others. Glyo-Fixx performed as well as formalin for overall morphology and provided highest nuclear detail and lymphocyte appearance scores. Omnifix II gave best results for cytoplasmic detail. CONCLUSION: In this blind study, formalin fixation provided the highest histomorphologic quality for tissue stained with hematoxylin-eosin and examined for diagnostic surgical pathology. Should the use of formalin be discontinued, pathologists will have to familiarize themselves with a different set of microscopic details associated with the replacement fixatives.