Pinealectomy interferes with the circadian clock genes expression in white adipose tissue

Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24‐hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev‐erbα, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24 hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP‐citrate lyase, malic enzyme, fatty acid synthase, and glucose‐6‐phosphate dehydrogenase) was abolished in pinealectomized animals.     

Evaluation of Patient-Reported Outcome in Subjects Treated Medically for Acute Pancreatitis: A Follow-Up Study

Aims: To explore the quality of life in patients treated medically during the acute phase of pancreatitis as well as at 2 and 12 months after discharge from the hospital. Patients: 40 patients were studied. The etiology of the pancreatitis was biliary causes in 31 patients and non-biliary causes in 9; mild disease was present in 29 patients and severe disease in 11. 30 patients completed the two surveys at 2 and 12 months after hospital discharge. Methods: The SF-12 and EORTC QLQ-C30 questionnaires were used for the purpose of the study. Results: The two physical and mental component summaries of SF-12, all the domains of EORTC QLQ-C30 (except for physical functioning and cognitive functioning) and some symptom scales of EORTC QLQ-C30 (fatigue, nausea/ vomiting, pain, and constipation) were significantly impaired during the acute phase of pancreatitis. There was a significant improvement in the SF-12 physical component summary, and global health, role functioning, social functioning, nausea/vomiting, pain, dyspnea, and financial difficulties (EORTC QLQ-C30) at 2 months after discharge as compared to the basal evaluation. Similar results were found after 12 months except for the mental component score at 12-month evaluation, which was significantly impaired in acute pancreatitis patients in comparison to the norms. The physical functioning of the EORTC QLQ-C30 at basal evaluation was significantly impaired in patients with severe pancreatitis in comparison to patients with mild pancreatitis. Conclusions: Two different patterns can be recognized in the quality of life of patients with acute pancreatitis: physical impairment is immediately present followed by mental impairment which appears progressively in the follow-up period.     

Assessment of the quality of life in chronic pancreatitis using Sf-12 and EORTC Qlq-C30 questionnaires

BACKGROUND: SF-12 Health Survey, and European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 are the two main questionnaires proposed and validated for assessing the quality of life in chronic pancreatitis. AIMS: To evaluate the role of the information furnished by both the SF-12 Health Survey and European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 questionnaires, and to determine which of these two questionnaires may be considered more efficacious, in clinical practice, in describing the quality of life of patients with chronic pancreatitis. PATIENTS: We studied 163 consecutive patients with proven chronic pancreatitis. METHODS: The Italian version of the SF-12 Health Survey and the Italian neutral version of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30 Version 3.0 questionnaires were administered. RESULTS: Pancreatic pain was the only clinical variable able to significantly impair the SF-12 Health Survey component summaries as well as all domains of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30, while body mass index was positively related to the physical component summary-12 and to the domains of the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30. A high level of reliability of the domains/scores of the two questionnaires in evaluating the quality of life in patients with chronic pancreatitis was found and two main factors were identified. These two factors were mainly related to the two SF-12 Health Survey summary components. CONCLUSIONS: From a practical point of view, the SF-12 Health Survey is more reliable and easier to use in routine clinical practice than the European Organisation for Research and Treatment of Cancer Quality of life Questionnaire-C30.     

The rate of development and time of transfer play different roles in influencing the viability of human blastocysts

Improved embryo culture protocols now render more feasible the possibility of obtaining human blastocysts after in-vitro fertilization. In this study we present: (i) results of blastocyst development from supernumerary embryos after co-culture on green monkey kidney epithelial cells and (ii) pregnancy rates after transfer of frozen blastocysts. In addition, we have examined the influence of the day of blastocyst freezing and the day of transfer after the luteinizing hormone (LH) peak on pregnancy and implantation rates. Of 423 supernumerary embryos, 200 developed to the blastocyst stage (47.3%). By days 5 and 6, 67% of the blastocysts had reached the blastocyst stage, and were frozen, compared to 28.5% by day 7. When we compared the cases where only blastocysts frozen on days 5 and 6 were transferred compared to those frozen and transferred on or after day 7 the pregnancy rates were 7/18 (38.9%) and 1/16 (6.2%) respectively. In contrast, when we examined the influence of the day of transfer we found that pregnancies were established from day 5 up to day 9 post LH peak. Based on these results, we suggest that every attempt should be made to increase the development rate of supernumerary embryos to the blastocyst stage, as it appears that the quality of blastocysts transferred, as shown in this study by rate of development, plays a more crucial role than the timing of transfer.      

Blastocyst development from supernumerary embryos after intracytoplasmic sperm injection: a paternal influence?

The success of intracytoplasmic sperm injection (ICSI) warrants further study on the role of paternal factors in early human embryogenesis. To investigate whether poor sperm parameters can influence embryo development, we examined the development of ICSI-fertilized embryos to the blastocyst stage. We present results of blastocyst development from supernumerary ICSI embryos after co-culture on monkey kidney epithelial cells. In addition, we compare the development of supernumerary embryos to the blastocyst stage after ICSI and in-vitro fertilization (IVF). Of 168 supernumerary ICSI embryos, 45 (26.8%) developed to blastocysts. Sperm concentration and morphology did not influence blastocyst development. In contrast, blastocysts arose from spermatozoa that had a significantly higher (P = 0.015) forward progressive motility compared with spermatozoa from those patients who failed to produce blastocysts (42.7% versus 28.2%, respectively). Overall the rate of embryo development to the blastocyst stage after ICSI was lower (26.8%) than that after IVF (47.3%). When the rate of blastocyst development was calculated for patients with three or more supernumerary embryos, it remained significantly higher for the IVF patients than for the ICSI patients (45.6% versus 30.0%). There was no significant difference in the mean cell number and quality of the supernumerary embryos between the IVF and ICSI patients. This study confirms previous reports that have postulated that abnormal spermatozoa may manifest a negative paternal effect on preimplantation embryo development.      

Concomitant association of radiotherapy and chemotherapy in inflammatory breast cancer. Initial results of phase II trial

Between 01/1986 and 12/1987, 15 patients displaying inflammatory breast carcinoma, were included in a phase II trial. The aim of the treatment was to increase the local response by the potentiation of radiotherapy by concomitant chemotherapy (continuous infusion 5 FU, vindésine, Cyclophosphamide). This treatment consisted of four series of radiotherapy: 18 Gy/10 fractions/12 days spaced by a 2-week rest period between series, to a total dose of 72 GY to the breast tumor. Chemotherapy was undertaken over the first 5 days of radiotherapy in each series. Two patients had metastatic disease (bone-liver). Seven patients had not responded to an initial standard chemotherapy treatment. Six patients were initially treated with the concomitant association. The treatment was very well tolerated by all 15 patients. Inflammation disappeared in all patients within 6 weeks after the beginning of the association. A tumor decrease was observed in all patients, complete in 60%. All 7 patients who had failed initial chemotherapy recurred 8 to 19 months after the association, despite a good response; 3 died of disease and 4 were in local or metastatic evolution on last follow up. The 6 patients treated initially with the association Radiotherapy/Chemotherapy were all alive with a 27 months median follow up (24-40). 2/6 mastectomies were performed: one for breast recurrence and one for persistent residual mass. In this latter patient histologic examination showed no residual active tumor. 4/6 patients have their breast preserved without sequelae. High local response rates were observed with the concomitant combination of radiotherapy and chemotherapy, specially when administered as initial treatment.     

Recombinant interleukin 2 and anti-Tac influence the growth of enriched multipotent hemopoietic progenitors: proposed hypotheses for different responses in early and late progenitors

Experiments were designed to evaluate the effect of recombinant IL-2 on growth of hemopoietic precursors from different sources (normal cord blood and bone marrow, and PB from CGL patients). For this purpose, combined cell sorting techniques and multipotent colony forming cell assays were used. A monoclonal antibody BI-3C5, which recognizes an antigen present on early lympho-myeloid cells as well as on all colony forming cells (CFU-GEMM assay), was used to enrich the studied populations. Double colour immunofluorescence techniques were performed to analyse the expression of Tac antigen on early progenitors. The results showed that rIL-2 had a stimulatory effect on growth of enriched progenitors from the three sources and surprisingly that addition of anti-Tac did not abolish this effect. On the contrary, anti-Tac enhanced even more growth of these sorted BI-3C5 precursors, suggesting a ligand action of the antibody. More interestingly, a low percentage of cord cells (1 in 1000) expressed both BI-3C5 and Tac antigens. The vast majority of cells did not concomitantly express both markers. The double labelled cells had a lymphoid-like morphology, high nucleus/cytoplasmic ratio and 2-3 nucleoli. The results will be discussed focusing on early and late "stem" cell growth.