The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor) was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin) and protein excretion rate (PER) were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P < .001), Cinulin increased 80% (P < .01). Kidney wet and dry weights increased 10%–12% (P < .05), and glomerular tuft area increased 9.3% (P < .001). Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.
Wound healing (WH) impairment is a well-documented phenomenon in clinical and experimental diabetes. Sex hormones, in addition to a number of signaling pathways including transforming growth factor-β1 (TGF-β1)/Smads and TNF-α/NF-κB in macrophages and fibroblasts, appear to play a cardinal role in determining the rate and nature of WH. We hypothesized that a defect in resolution of inflammation and an enhancement in TNF-α/NF-κB activity induced by estrogen deficiency contribute to the impairment of TGF-β signaling and delayed WH in diabetes models. Goto-Kakizaki (GK) rats and full thickness excisional wounds were used as models for type 2 diabetes (T2D) and WH, respectively. Parameters related to the various stages of WH were assessed using histomorphometry, western blotting, real-time PCR, immunofluorescence microscopy and ELISA-based assays. Retarded re-epithelialization, suppressed angiogenesis, delayed wound closure, reduced estrogen level and heightened states of oxidative stress were characteristic features of T2D wounds. These abnormalities were associated with a defect in resolution of inflammation, shifts in macrophage phenotypes, increased β3-integrin expression, impaired wound TGF-β1 signaling (↓p-Smad2/↑Smad7) and enhanced TNF-α/NFκB activity. Human/rat dermal fibroblasts of T2D, compared to corresponding control values, displayed resistance to TGF-β-mediated responses including cell migration, myofibroblast formation and p-Smad2 generation. A pegylated form of soluble TNF receptor-1 (PEG-sTNF-RI) or estrogen replacement therapy significantly improved re-epithelialization and wound contraction, enhanced TGFβ/Smad signaling, and polarized the differentiation of macrophages toward an M2 or "alternatively" activated phenotype, while limiting secondary inflammatory-mediated injury. Our data suggest that reduced estrogen levels and enhanced TNF-α/NF-κB activity delayed WH in T2D by attenuating TGFβ/Smad signaling and impairing the resolution of inflammation; most of these defects were ameliorated with estrogen and/or PEG-sTNF-RI therapy.
Endometriotic nodules need to be differentiated from other benign/malignant masses and evaluated for possible malignant transformation. FNAC provides a safe and effective tool for diagnosis thereby obviating the need for other procedures.
Abstract. in the present study, the expression of estrogen receptor (Er)α and Erβ isoforms in Er-positive (mcF7, t-47d and Zr-75-1) and Er-negative (mda-mB-231, SK-Br-3, mda-mB-453 and hcc1954) breast cancer cell lines was investigated. Erα mrna was expressed in Er-positive and some Er-negative cell lines. Erα ∆3, ∆5 and ∆7 spliced variants were present in mcF7 and t-47d cells; Erα ∆5 and ∆7 spliced variants were detected in ZR-75-1 cells. mda-mB-231 and hcc1954 cells expressed Erα ∆5 and ∆7 spliced variants. the Erβ1 variant was expressed in all of the cell lines and the Erβ2 variant in all of the Er-positive and some Er-negative cell lines (mda-mB-231, mda-mB-453 and SK-Br-3). mcF7, Zr-75-1, mda-mB-453, hcc1954 and t-47d cells expressed Erβ5. all cell lines expressed an Erα 66-kda protein band, and some expressed the truncated 42-kda variant. Erβ1 was detected in all of the cell lines in addition to a 38-44 kda variant. the results indicate that breast cancer cell lines widely used in research and reported as being Er-negative express Erα and/or Erβ mrna and protein.
It is commonly believed that cytodiagnosis of Hodgkin's lymphoma (HL) is much easier than that of non-Hodgkin lymphoma (NHL). However, recognition of certain NHL subtypes with Reed-Sternberg (R-S)-like cells and results of immunohistochemical studies point to the contrary. To study the limitations of cytology in diagnosis of HL, fine-needle aspiration (FNA) smears of 130 lymphoma or suspected lymphoma cases were reviewed. Initial and reviewed cytodiagnoses were compared with histopathology in 89 cases. Immunocytochemical and immunohistochemical studies were performed in 56 and 59 cases, respectively. Among histologically diagnosed HL cases, definitive cytodiagnosis of HL (initial as well as reviewed) was significantly less frequent than cytodiagnosis of NHL among histologically diagnosed NHL cases (P = 0.0328 and = 0.0001, respectively). On the other hand, cytologically diagnosed HL/NHL cases were significantly more frequent in the former group (P = 0.0001 and = 0.0018, respectively). ALCL and TCRBCL were the two NHL subtypes which created confusion with HL in FNA smears. Twenty-one cytohistological concordant HL cases and equal number of discordant cases were compared. When compared with discordant group, the patients in concordant group were significantly younger (P = 0.045). Hodgkin/Hodgkin-like cells and typical R-S cells were significantly more frequent in FNA smears of the concordant group (P = 0.0478 and = 0.0431, respectively). Immunocytochemical and immunohistochemical studies showed good correlation with histological diagnosis of HL. It is suggested that proper interpretation of cytologic features, together with use of immunocytochemical parameters can help in reducing the margin of error in cytodiagnosis of HL.
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