Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinases TIMP-3 and -4 in benign endometrium and endometrial cancer

OBJECTIVE: Matrix metalloproteinases (MMPs) and their physiological inhibitors, the tissue inhibitors of MMPs (TIMPs), play a key role in tumor cell invasion, angiogenesis, and growth. The aim of this study was to determine the expression and cellular distribution of MMP-26, TIMP-3, and TIMP-4 in endometrial cancers and benign endometrium throughout the menstrual cycle and the correlation with tumor histological subtype, stage, and grade. METHODS: Immunohistochemical analysis using polyclonal antibodies generated against pro- and active MMP-26, and mono- and polyclonal antibodies specific to TIMP-3 and TIMP-4, respectively, was performed. RESULTS: MMP-26, TIMP-3, and TIMP-4 are expressed in endometrial carcinomas (N = 86) and benign endometrium (N = 50) from various stages of the menstrual cycle. Semi-quantitative analysis of staining intensity indicated that endometrial carcinomas expressed more MMP-26, TIMP-3, and TIMP-4 compared to benign endometrium from the postmenopausal period, but not from the secretory phase of the menstrual cycle. The highest staining intensity was associated with endometrial epithelial cells, followed by vascular endothelial cells, myometrial smooth muscle cells, and endometrial stromal cells. Increased staining intensity of MMP-26 and TIMP-3 correlated with grade III tumors and MMP-26 and TIMP-4 with the depth of myometrial invasion in tumors histologically characterized as endometrioid adenocarcinoma, clear-cell, and papillary serous carcinoma staged/graded based on FIGO criteria. CONCLUSION: MMP-26 and TIMP-4 are expressed in endometrium and endometrial carcinoma and their elevated expression and correlation with myometrial invasion suggests that MMP-26 and TIMP-4 may play a key role in endometrial tumor progression.     

Immunocontraceptive potential of recombinant bonnet monkey (Macaca radiata) zona pellucida glycoprotein-C expressed in Escherichia coli and its corresponding synthetic peptide

Zona pellucida (ZP) glycoproteins have been proposed as candidate antigens for development of immunocontraceptive vaccines. In this study, the efficacy to block fertility by immunization with recombinant bonnet monkey (Macaca radiata) zona pellucida glycoprotein-C (r-bmZPC) expressed in Escherichia coli and its synthetic peptide (P(4): KGDCGTPSHSRRQPHVVSQWSRSA, aa residues 324-347) conjugated to diphtheria toxoid (DT) has been evaluated in a homologous system. Female bonnet monkeys, immunized with P(4)-DT conjugate showed better immunocontraceptive potential as compared to an r-bmZPC-DT immunized group. In spite of high anti-P(4) antibody titres, animals continued to have ovulatory cycles and showed no disturbance in cyclicity (except summer amenorrhoea). No ovarian pathology was observed in the P(4) immunized group. These results suggest that immunization with the P(4) may lead to block in fertility without obvious ovarian dysfunction. However, further inputs are required to identify additional ZP based B-cell epitopes to enhance the contraceptive efficacy.     

Diabetic ketoacidosis and its treatment increase plasma 3-deoxyglucosone

OBJECTIVES: Highly reactive dicarbonyl compounds are known to be increased by hyperglycemia, ketone bodies and lipid peroxidation. This study was carried out to investigate the effect of diabetic ketoacidosis (DKA) and its treatment on the plasma concentration of 3 deoxyglucosone (3-DG) one of the dicarbonyl compounds. DESIGN AND METHODS: 3-DG was measured in 7 children before, during and following correction of severe DKA. 3-DG was elevated before treatment (610 nmol/L +or/- 70) in comparison to baseline (120 h) (200 nmol/L+/or- 17) (p < 0.05). At 6 to 24 h into treatment 3-DG was further elevated (1080 nmol/L +or/- 80) in comparison to both pretreatment (p < 0.05) and baseline (p < 0.05). CONCLUSION: 3-DG is significantly elevated before the treatment of DKA and increases further during the treatment of DKA. The time course of the increase of 3-DG coincides with the time of progression of subclinical brain edema, which occurs in DKA.     

Sinonasal neuro endocrine carcinoma extending into orbit — a case report

Small Cell Neuroendocrine Carcinomas of the Sinonasal tract are extremely uncommon and distinct neoplasms with aggressive clinical behavior. They have similar morphological and immunohistochemical features to those of small cell carcinomas of the lung. They should be distinguished from Olfactory Neuroblastomas. We report a case of this rare entity. A 46-year-old woman presented with a history of injury to the right eye with facial pain and proptosis as the primary symptoms. Later she developed nasal stuffiness. C.T. Scan revealed a space occupying lesion in the right nostril extending into ethmoid sinus and orbit. Functional endoscopic sinus surgery was done with decompression of the orbit. The biopsy material was obtained from ethmoid sinus and orbit. Histopathological examination of the biopsy specimen along with Immunohistochemical stains confirmed a Small Cell Neuroendocrine Carcinoma. Patient was treated with Radiotherapy and chemotherapy and responded well.     

Immunogenic and genetic factors in rheumatic fever

Although rheumatic fever has virtually disappeared in many developed countries, it remains the number one acquired heart disease among children in developing countries. Many hypotheses advanced to explain the pathogenic mechanisms of this disease include the concept of an abnormal humoral and cellular response within the host to streptococcal antigens cross-reacting with mammalian tissues. This report examines the most recent evidence supporting this concept. It emphasizes the importance of the cellular arm of the immune response in cardiac damage, as wall as possible genetic disposition to the disease.     

Fasting ghrelin is related to skeletal muscle mass in healthy adults

Background/Objectives  

The determinants of plasma ghrelin concentrations including the effects of aging, gender, and body composition, are unclear. Appetite and energy intake decrease with advancing age, and there is a corresponding decline in total body lean tissue, and an increase in fat mass.