Ineffective correction of PPARγ signaling in cystic fibrosis airway epithelial cells undergoing repair.

Peroxisome proliferator-activated receptor gamma (PPARγ) represents a potential target to treat airway mucus hypersecretion in cystic fibrosis (CF). We aimed to determine if PPARγ is altered in CF human airway epithelial cells (HAECs), if PPARγ contributes to mucin expression and HAEC differentiation, and if PPARγ ligand therapy corrects the CF phenotype. To this end, well-differentiated CF and NCF HAEC primary cultures were wounded to monitor the expression of key genes involved in PPARγ activation and mucus homeostasis, and to evaluate the effect of a PPARγ agonist, at different times of repair. Hydroxyprostaglandin dehydrogenase (HPGD) converts prostaglandin E2 to 15-keto PGE2 (15kPGE2), an endogenous PPARγ ligand. Interestingly, PPARγ and HPGD expression dramatically decreased in CF HAECs. These changes were accompanied by an increase in the expression of MUC5B. The correlation between PPARγ and MUC5B was confirmed in an airway epithelial cell line after CFTR knock-down. Exposure of HAECs to 15kPGE2 did not correct the CF phenotype but revealed a defect in the process of basal cell (BC) differentiation. The HPGD/PPARγ axis is deregulated in primary HAEC cultures from CF patients, which may impact the maturation of BCs to differentiated luminal cells. Importantly, PPARγ therapy was inefficient in correcting the CF defect.

A case of mesothelioma masquerading pre-operatively as ovarian cancer and brief review of the literature.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) can masquerade as an ovarian epithelial neoplasm, with very similar presenting clinical symptoms and imaging findings. The gold standard in differentiating between these two diagnoses lies in tissue pathology. CASE REPORT: This is a case of MPM that was initially misdiagnosed as ovarian cancer based on family history, imaging, and surgical findings. Tissue diagnosis preoperatively would have changed the planned procedure. Retrospectively, after the diagnosis of MPM, the patient was found to have had an indirect exposure to asbestos through her father. CONCLUSIONS: This case highlights the importance of keeping a broad differential when diagnosing ovarian malignancies, collecting both family and social histories (including screening for exposure to asbestos), and the benefit of obtaining tissue diagnosis when MPM is suspected.

Cx26 regulates proliferation of repairing basal airway epithelial cells.

The recovery of an intact epithelium following injury is critical for restoration of lung homeostasis, a process that may be altered in cystic fibrosis (CF). In response to injury, progenitor cells in the undamaged areas migrate, proliferate and re-differentiate to regenerate an intact airway epithelium. The mechanisms regulating this regenerative response are, however, not well understood. In a model of circular wound injury of well-differentiated human airway epithelial cell (HAEC) cultures, we identified the gap junction protein Cx26 as an important regulator of cell proliferation. We report that induction of Cx26 in repairing HAECs is associated with cell proliferation. We also show that Cx26 is expressed in a population of CK14-positive basal-like cells. Cx26 silencing in immortalized cell lines using siRNA and in primary HAECs using lentiviral-transduced shRNA enhanced Ki67-labeling index and Ki67 mRNA, indicating that Cx26 acts a negative regulator of HAEC proliferation. Cx26 silencing also markedly decreased the transcription of KLF4 in immortalized HAECs. We further show that CF HAECs exhibited deregulated expression of KLF4, Ki67 and Cx26 as well enhanced rate of wound closure in the early response to injury. These results point to an altered repair process of CF HAECs characterized by rapid but desynchronized initiation of HAEC activation and proliferation.

Salting-out phenomenon and 1-octanol/water partition coefficient of metalaxyl pesticide.

In this paper, we present the effect of inorganic cations such as Na+, K+, Ca2+, Mg2+ on the salting-out phenomenon of metalaxyl from pure water to aqueous salt solutions. Moreover the 1-octanol/water partition coefficient in pure water is presented. To accomplish this, aqueous solubility of metalaxyl was determined in pure water, in different salt solution (NaCl, KCl, CaCl2 and MgCl2), and at different concentration level ranging from 0.01 to 1.5 M. The 1-octanol/water partition coefficient was determined using the static shake-flask method. Solubility was determined using dynamic saturation method for pure water in the range of 298.15-325.15 K and at 298.15 K for different salt solutions. The solubility value in pure water for studied interval was found constant (m=3.118×10(-2) mol kg(-1)). Solubility values were used to calculate the standard molar Gibbs free energy of dissolution (ΔsolG°) and transfer (ΔtrG°) at 298.15 K. The values of ΔtrG° from pure to all studied aqueous salt solutions did not exceed 2 kJ mol(-1), the value of ΔsolG° of dissolution is 18.5 ±0.72 kJ mol(-1). The 1-octanol/water partition coefficient in pure water log Ko/w is equal to 1.69. The obtained results confirm the classification of the neutral metalaxyl as a slightly hydrophobic molecule.

Atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and histology.

OBJECTIVE: A new terminology for cytologic diagnosis of cervical lesions has been introduced by Bethesda System. This includes: 1) Atypical squamous cells of undetermined significance (ASCUS), 2) Low-grade squamous intraepithelial lesion (LSIL), 3) High-grade squamous intraepithelial lesion (HSIL), 4) squamo-cellular carcinoma. The aim of this study was to assess the correlation between the colpocytologic test (Pap psmear), the histologic response and colposcopy. METHODS: We re-examined the cytologic results of 447 patients who underwent routine cytologic tests, with a diagnosis of various grades of atypia, from ASCUS to HSIL. A histologic test was carried out on a colposcopic basis in 210 cases and cytologic results were correlated with the histologic and colposcopic pictures. RESULTS: For ASCUS the histology was positive in 19.1% (31/163) of cases and negative in 10.4% of the colposcopically positive cases (17/163), while in the remaining 70.5% (115/163) the colposcopy resulted negative. In LSIL with the presence of human papillomavirus (HPV) the histologic findings, confirmed the cytologic result in 35.8% (48/134) while in the group of cervical intraepithelial neoplasia (CIN I) results corresponded in 40.6% (41/101). In high squamous intraepithelial lesions there was an histologic confirmation in 59.2% (29/49). CONCLUSIONS: The data obtained indicate an increase in positive histology results from the types of low grade (ASCUS-LSIL) to those of a high grade (HSIL). Our results indicate that the presence of ASCUS should be assessed colposcopically and histologically, where indicated.