Search

AprX is an alkaline metalloprotease produced by Pseudomonas spp. and encoded by its initial gene of the aprX-lipA operon. The intrinsic diversity among Pseudomonas spp. regarding their proteolytic activity is the main challenge for the development of accurate methods for spoilage prediction of ultra-high temperature (UHT) treated milk in the dairy industry. In the present study, 56 Pseudomonas strains were characterized by assessing their proteolytic activity in milk before and after lab-scale UHT treatment. From these, 24 strains were selected based on their proteolytic activity for whole genome sequencing (WGS) to identify common genotypic characteristics that correlated with the observed variations in proteolytic activity. Four groups (A1, A2, B and N) were determined based on operon aprX-lipA sequence similarities. These alignment groups were observed to significantly influence the proteolytic activity of the strains, with an average proteolytic activity of A1 > A2 > B > N. The lab-scale UHT treatment did not significantly influence their proteolytic activity, indicating a high thermal stability of proteases among strains. Amino acid sequence variation of biologically-relevant motifs in the AprX sequence, namely the Zn 2+ -binding motif at the catalytic domain and the C-terminal type I secretion signaling mechanism, were found to be highly conserved within alignment groups. These motifs could serve as future potential genetic biomarkers for determination of alignment groups and thereby strain spoilage potential., Competing Interests: Declaration of competing interest Piccini, V., Rauh, V. and Xiao, Y. are employed by Arla Foods Amba. The other authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Hypoparathyroidism is a rare disease characterized by low serum calcium levels and absent or deficient parathyroid hormone level. Regarding the epidemiology of chronic hypoparathyroidism, there are limited data in Italy and worldwide. Therefore, the purpose of this study was to build a unique database of patients with chronic hypoparathyroidism, derived from the databases of 16 referral centers for endocrinological diseases, affiliated with the Italian Society of Endocrinology, and four centers for endocrine surgery with expertise in hypoparathyroidism, to conduct an epidemiological analysis of chronic hypoparathyroidism in Italy. The study was approved by the Institutional Review Board. A total of 537 patients with chronic hypoparathyroidism were identified. The leading etiology was represented by postsurgical hypoparathyroidism (67.6%), followed by idiopathic hypoparathyroidism (14.6%), syndromic forms of genetic hypoparathyroidism (11%), forms of defective PTH action (5.2%), non-syndromic forms of genetic hypoparathyroidism (0.9%), and, finally, other forms of acquired hypoparathyroidism, due to infiltrative diseases, copper or iron overload, or ionizing radiation exposure (0.7%). This study represents one of the first large-scale epidemiological assessments of chronic hypoparathyroidism based on data collected at medical and/or surgical centers with expertise in hypoparathyroidism in Italy. Although the study presents some limitations, it introduces the possibility of a large-scale national survey, with the final aim of defining not only the prevalence of chronic hypoparathyroidism in Italy, but also standards for clinical and therapeutic approaches.

Context: Adrenocortical carcinoma (ACC) is a rare malignancy, the prognosis of which is mainly dependent on stage at diagnosis. The identification of disease-associated markers for early diagnosis and drug monitoring is mandatory. Circulating tumor cells (CTCs) are released into the bloodstream from primary tumor/metastasis. CTC detection in blood samples may have enormous potential for assisting in the diagnosis of malignancy, estimating prognosis, and monitoring the disease., Objective: The aim of the study was to investigate the presence of CTCs in blood samples of patients with ACC or benign adrenocortical adenoma (ACA)., Setting: We conducted the study at a university hospital., Intervention: CTC analysis was performed in blood samples from 14 ACC patients and 10 ACA patients. CTCs were isolated on the basis of cell size by filtration through ScreenCell devices, followed by identification according to validated morphometric criteria and immunocytochemistry., Main Outcome Measure: We measured the difference in CTC detection between ACC and ACA., Results: CTCs were detected in all ACC samples, but not in ACA samples. Immunocytochemistry confirmed the adrenocortical origin. When ACC patients were stratified according to the median value of tumor diameter and metastatic condition, a statistically significant difference was found in the number of CTCs detected after surgery. A significant correlation between the number of CTCs in postsurgical samples and clinical parameters was found for tumor diameter alone., Conclusions: Our findings provide the first evidence for adrenocortical tumors that CTCs may represent a useful marker to support differential diagnosis between ACC and ACA. The correlation with some clinical parameters suggests a possible relevance of CTC analysis for prognosis and noninvasive monitoring of disease progression and drug response.

Head and neck paragangliomas (HNPGLs) are neural crest-derived tumors. In comparison with paragangliomas located in the abdomen and the chest, which are generally catecholamine secreting (sPGLs) and sympathetic in origin, HNPGLs are, in fact, parasympathetic in origin and are generally nonsecreting. Overall, 79 consecutive patients with HNPGL were examined for mutations in SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, MAX, and TMEM127 genes by PCR/sequencing. According to a detailed family history (FH) and clinical, laboratory (including metanephrines), and instrumental examinations, patients were divided into three groups: a) patients with a positive FH for HNPGL (index cases only), b) patients with a negative FH and multiple HNPGLs (synchronous or metachronous) or HNPGL associated with an sPGL, and c) patients with negative FH and single HNPGL. The ten patients in group a) proved to be SDHD mutation carriers. The 16 patients in group b) proved to be SDHD mutation carriers. Among the 53 patients in group c), ten presented with germ-line mutations (three SDHB, three SDHD, two VHL, and two SDHAF2). An sPGL was found at diagnosis or followed up in five patients (6.3%), all were SDHD mutation carriers. No SDHC, SDHA, MAX, and TMEM127 mutations were found. In SDHD mutation carriers, none of the patients affected by HNPGL associated with sPGL presented missense mutations. In conclusion, a positive FH or the presence of multiple HNPGLs is a strong predictor for germ-line mutations, which are also present in 18.8% of patients carefully classified as sporadic. The most frequently mutated gene so far is SDHD but others, including SDHB, SDHAF2, and VHL, may also be affected.

PPAR-γ is a member of the nuclear hormone receptor superfamily of transcription factors, whose thiazolidinedione ligands (TZD) have been recently demonstrated to also possess anticancer properties in addition to their well-known insulin-sensitizer and glucose/lipid regulation activity. In this minireview, we summarize the current knowledge on PPAR-γ in normal and tumoral corticotropic pituitary and adrenal cells. The receptor expression has been shown in ACTH-secreting cells in both normal and adenomal pituitary as well as in normal and tumor adrenal cortex. Preclinical studies conducted both in vitro on tumor cells and in vivo on xenograft tumor models obtained by subcutaneous injection of cancer cells have evidenced the anticancer properties of TZD, in particular rosiglitazone (RGZ) and pioglitazone (PIO). In both pituitary and adrenocortical cancer, RGZ treatment results in inhibition of cell proliferation, through G0/G1 cell-cycle arrest and induction of cell apoptosis, leading to significant inhibition of tumor growth in the xenograft tumor models. In addition, since RGZ can reduce ACTH and corticosterone secretion in mouse corticotropic pituitary tumors, both RGZ and PIO have been used in the treatment of Cushing's disease with variable but generally unsatisfactory results. Discrepancies in the antitumor effects of TZD observed between successful preclinical and unsuccessful clinical studies may be particularly due to differences in treatment duration and doses used., (Copyright © 2010 S. Karger AG, Basel.)

Purpose: To explore the expression of fatty acid synthase (FAS) and human erythrocyte glucose transporter 1 (GLUT1) in endometrial carcinomas and to detect associations with clinicopathological features and prognosis. FAS and GLUT1 are two molecules involved in energy supply of normal cells. These markers are overexpressed in neoplastic tissues because of their increased necessity of energy., Methods: Ninety-five patients with endometrial carcinoma were followed-up for an average period of 5 years. FAS and GLUT1 expressions were evaluated by immunohistochemistry on formalin-fixed paraffin-embedded tissues. Staining was determined with a semiquantitative method. Negative controls were obtained from patients submitted to hysterectomy for uterine prolapse., Results: Eighty-five cases were endometrioid, 7 were serous, and 1 was a mucinous carcinoma. Seventy-two cases (75%) were stage I, 12 (13%) were stage II, and 11 (12%) were stage III carcinomas. Sixteen (15%) carcinomas recurred. Nine patients (8%) died for cancer during the follow-up period. FAS expression was observed in 53 cases (56%). GLUT1 expression was observed in 32 (43%) cases. Statistical analysis revealed that FAS (P = 0.04) and stage (P = 0.001) of the disease were the only two independent predictors of recurrence. GLUT1 and other clinicopathologic parameters had no prognostic association., Conclusions: FAS is a reliable marker of clinically aggressive endometrial carcinomas. The knowledge of FAS expression in endometrial carcinomas is an important finding that may stratify patients into selected groups and determine therapeutic approaches for patient care.

56 very low-birth-weight (less than or equal to 1500 gm) infants were admitted in our Neonatal Intensive Care Unit between january 1978 and december 1981. Mortality of these infants in the first year of life decreased from 50% in 1978 to 32% in 1981. Our study confirms that mortality is significantly higher in transported infants. As to those born in our Hospital, mortality is markedly higher for breech delivery than for cephalic delivery or caesarian section. The amelioration of intensive care techniques, i.e. continuous transcutaneous PaO2 monitoring, orotracheal intubation at birth and improved respiratory care, markedly reduced the percentage of children with neuromotor pathology (from 43% in 1978 to 0% in 1981 in 16 survivors). Neurological follow-up was performed by serial controls until at least 2 years of age; Apgar scores and blood gas values are reported along with follow-up results to evaluate prognostic significance. Duration of orotracheal intubation, isolette requirement and feeding schedules are briefly discussed.