Involvement of A1 adenosine receptors in the acquisition of fertilizing capacity

Ejaculated mammalian spermatozoa acquire competence to fertilize oocytes by a two-step process: capacitation followed by acrosome reaction. The biochemical and biophysical modifications occurring in vivo in the female reproductive tract can be reproduced in vitro, and previous studies have suggested a capacitative role for adenosine A(1) receptor (A(1)R). Mice with a targeted disruption of the Adora 1 gene (A(1)R-/- mice) provide a useful model for better understanding the role of the A(1)R in fertility. Murine spermatozoa express A(1)R in the head, neck, midpiece region, and tail. The number of capacitated spermatozoa incubated in human tubal fluid was significantly reduced in A(1)R-/- compared with A(1)R+/+ and A(1)R+/- spermatozoa. The difference between A(1) R+/+ and A(1)R-/- mouse spermatozoa was mainly in the time necessary to reach the maximum percentage of capacitation. A(1)R+/+ murine sperm obtained the full state of capacitation within 90 minutes whereas A(1)R-/- sperm required 240 minutes. Caffeine, a known antagonist of A(1) and A(2A) adenosine receptors, lowered the number of capacitated sperm and affected the time of capacitation in a dose-dependent manner, mimicking the effects of the lack of A(1) receptors. Although number, motility, and viability of A(1)R-/- murine sperm was not significantly different from A(1)R+/+ mouse spermatozoa, a significant reduction of the number of pups produced by A(1)R-/- male mice suggests that A(1) receptors must be fully operative to accomplish the optimal degree of capacitation and thereby fertilization.     

Expression of c-kit proto-oncogene product in breast tissue

The proto-oncogene c-kit encodes a transmembrane tyrosine kinase growth factor receptor. Stem cell factor, the receptor ligand, plays an important role in the development of certain neoplasms. c-kit is selectively and competitively bound by STI-571, a newly developed tyrosine kinase inhibitor. Several investigators report conflicting results concerning its expression, especially in malignant breast lesions. The objective of this study was to better characterize the expression of c-kit within the spectrum of breast epithelium (normal breast epithelium, nonneoplastic lesions, and breast carcinoma). Seventy-seven randomly selected breast tissue samples, each containing normal breast epithelium (21), invasive breast carcinoma (41), in situ breast carcinoma (29), papilloma (8), fibroadenoma (5), fibrocystic change (11), and/or metastatic breast carcinoma (4), were immunostained with polyclonal rabbit antihuman c-kit (Dako, Carpenteria, CA) at a dilution of 1:200. The staining was interpreted as negative if no cells were immunoreactive, weak positive if 5% of the cells were immunoreactive, and positive if more than 5% of the cells were immunoreactive. Appropriate positive and negative controls were used. The observed staining was cytoplasmic, with highlighting of the nuclear membrane. Normal breast epithelium was positive in all cases. More than half of the cases of hyperplastic changes and benign neoplasms (fibroadenoma and papilloma) were positive. Only 10% of invasive and in situ carcinomas showed positivity for c-kit. c-kit is consistently expressed in normal breast epithelium, variably expressed in benign breast lesions, and poorly expressed in breast carcinoma. These data suggest that c-kit may play a role in breast tumor progression and may therefore have diagnostic, prognostic, and therapeutic implications.     

Lymphoepithelioma-like carcinoma of the breast: report of a case mimicking lymphoma

Only 10 cases of lymphoepithelioma-like carcinoma of the breast have been reported in the literature. This report adds one more case to the published literature. A 62-year-old woman presented with a mass in her left breast on physical examination. The mammographic images showed a 3.0 cm, poorly defined mass in the upper outer quadrant. A biopsy was recommended. The gross specimen consisted of a 5 cm portion of breast parenchyma with no discrete tumor. On microscopic examination, the tumor was composed of sheets of epithelioid cells arranged as single cells or in cords partially obscured by a dense lymphocytic infiltrate. The epitheliod cells extensively expressed cytokeratin stain, but did not express E-cadherin. The lymphoid cells expressed L26 stain in the germinal centers, and CD3 stain in the T lymphocytes surrounding the germinal centers and in between tumor cells. In situ hybridization showed no evidence of Epstein-Barr virus infection in the tumor cells. An overall review of 11 cases shows that the disease is usually seen in older patients. In situ and invasive lobular component was reported in 36% of the cases. Eight of 11 were negative for E-cadherin, 36% were estrogen receptor-positive, 18% were progesterone receptor-positive, and all of them were HER2/neu negative. None of the reported cases have been associated with Epstein-Barr virus infection. Only two of the cases showed lymph node metastasis, and long-term follow-up in one of them showed good prognosis. In summary, lymphoepithelioma-like carcinoma of the breast is a tumor with a good prognosis that should be considered as a possible diagnosis in breast tumors with an intense lymphocytic infiltrate.     

Procalcitonin levels in plasma in oncohaematologic patients with and without bacterial infections

Background: The flogosis markers currently in use show both low sensitivity and specificity, particularly in neoplastic and degenerative diseases. Procalcitonin (PCT) is a pro-peptide of calcitonin produced mainly but not only in the C-cells of the thyroid glands and, as several studies show, PCT levels in plasma increase during infections. Bacterial infections are also the main cause of death in oncological patients. Furthermore, in patients with leukaemia in chemotherapy recovery, infections often induce relapses. The aim of the present study is to detect PCT levels in plasma in oncohaematologic patients with and without infections. Methods: The study was carried out on 54 patients by a quantitative automated immunoassay. Results: PCT plasma levels ≥0.5 ng were detected in 27 out of 30 patients (90,0%) with bacterial infections; 8 out of 9 patients (88,9%) with viral infections and in 12 out of 15 patients in the control group without statistically significant differences. Conclusions: The results, which differ from those in the literature, are discussed.     

Cholelithiasis and renal cysts: simultaneous laparoscopic treatment

Laparoscopic surgery has been increasingly used in different fields of surgery. This report concerns the authors' experience with combined laparoscopic cholecystectomy and symptomatic renal cyst decortication. The mean diameter of the cysts was 11.2 cm. and involved the left and right kidney in 3 and 1 patient, respectively. All cysts were peripheral. Surgery was performed using 4 trocars in 3 cases and 5 trocars in the other. The mean operative time was 110 minutes and mean blood loss 40 cc. Postoperative pain was minimal. The mean duration of postoperative ileus was 2.2 days. No significant complications were observed. The mean postoperative hospital stay was 3.5 days. At follow-up examinations all patients were pain-free. Recurrence of the cyst was observed in only one case. Combined laparoscopic cholecystectomy and renal cyst decortication is technically feasible in selected cases and does not seem to significantly affect the perioperative course of cholecystectomy.     

Placental mesenchymal dysplasia associated with hepatic mesenchymal hamartoma in the newborn.

Placental mesenchymal dysplasia is an uncommon disorder in which the placenta is enlarged with abnormal, large, and often cystic villi with dilated and/or thick-walled vessels. These placental changes can mimic a partial hydatidiform mole but in contrast to a partial mole can coexist with a fully viable fetus. Fetal anatomical and vascular anomalies frequently coexist with placental mesenchymal dysplasia. In this case, placental mesenchymal dysplasia was associated with preterm labor at 33 weeks' gestation, fetal compromise, and a large abdominal mass with a large hepatic cyst that was de-roofed at exploratory laparotomy. The neonate remained critically ill with hypoxic ischaemic encephalopathy and coagulopathy and died despite intensive care. Biopsy and autopsy findings showed a large cystic mesenchymal hamartoma affecting the left lobe of the liver. This appears to be the 3rd histologically confirmed association of placental mesenchymal dysplasia with mesenchymal hamartoma of the liver in the English language literature.     

Clinical, histopathologic, and biologic features of pleomorphic lobular (ductal-lobular) carcinoma in situ of the breast: a report of 24 cases.

We reviewed 10 cases of pleomorphic lobular (ductal lobular) carcinoma in situ (PL/DLCIS) of the breast and compared them with 14 cases of pleomorphic lobular carcinoma in situ (PLCIS) found in association with invasive pleomorphic lobular carcinoma. The histologic features; immunohistochemical staining for estrogen receptors (ERs), p53, Ki67, E-cadherin, and gross cystic disease fluid protein-15 (GCDFP-15); and results of fluorescence in situ hybridization for HER-2/neu gene amplification were evaluated in all 24 cases. Histologically, PL/DLCIS cells were similar to those of PLCIS with invasion in that they were discohesive and medium to large in size with moderate to marked nuclear pleomorphism, small to prominent nucleoli, and moderate to abundant eosinophilic or vacuolated cytoplasm. In both groups, central necrosis was present in a small number of cases, and classic LCIS coexisted with the in situ lesion in less than half of the cases; in situ carcinomas were positive for ERs in 23 (100%) of 23 cases, p53 in 6 (25%) of 24 cases, and GCDFP-15 in 14 (74%) of 19 cases. The percentage of Ki67-positive tumor nuclei indicated moderate to high (more than 20%) proliferative activity in 8 (47%) of 17 cases. Immunostaining for E-cadherin was negative in all 24 cases. HER-2/neu gene amplification was observed in 1 (4%) of 23 cases. In cases with associated invasion, PLCIS had cytologic features and immunostaining patterns similar to those of the invasive pleomorphic component. Seven of the 10 patients who had PL/DLCIS without invasion underwent lumpectomy or simple mastectomy. Six of these patients had no evidence of disease in follow-up periods ranging from 4 to 32 months; the seventh patient developed recurrent disease 12 months after undergoing lumpectomy. We conclude that the cytologic features and biomarker expression profile of PL/DLCIS are similar to those of PLCIS with invasion but somewhat different from those of classic LCIS and ductal carcinoma in situ. Long-term follow-up studies are needed to further define the natural history of PL/DLCIS and its optimal management.     

Micronized palmitoylethanolamide reduces joint pain and glial cell activation

Objective and design

Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation.

Materials and subject

TMJ was induced in rats with the injection of complete Freund’s adjuvant (CFA) emulsion into the left TMJ capsule.

Treatment

The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity.

Methods

Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection.

Results

CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1.

Conclusions

The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.