An assessment of enteric nervous system and estroprogestinic receptors in obstructed defecation associated with rectal intussusception

Background The pathophysiological basis of obstructed defecation (OD) is still incompletely understood. In particular, few or no data are available concerning the enteric nervous system (ENS) in this condition. We investigated ENS abnormalities in patients with OD, undergoing surgery, together with the presence of estrogen (α and β) and progesterone receptors, and compare the results with those obtained in controls. Methods Full‐thickness rectal samples were obtained from 17 patients undergoing stapled transanal rectal resection for OD associated with rectal intussusception. Samples were analyzed by immunohistochemistry for enteric neurons, enteric glial cells, interstitial cells of Cajal (ICC), and for estrogen and progesterone receptors. Data were compared with those obtained in 10 controls. Key Results No differences between patients and controls were found for enteric neurons, whereas (compared with controls) OD patients displayed a significant decrease of enteric glial cells in both the submucous (P = 0.0006) and the myenteric (P < 0.0001) plexus. ICC were significantly increased in patients in the submucosal surface (P < 0.0001) and the myenteric area (P < 0.0001). Concerning estroprogestinic receptors, both were present on ICC in patients and controls. Estrogen receptors α and progesterone receptors were absent on enteric neurons and enteric glial cells in patients and controls, whereas estrogen receptors β were present in all controls and in 69% of patients’ enteric neurons (P = 0.18) and in 12% of patients’ glial cells (P = 0.0001). Conclusions & Inferences Patients with OD associated to rectal intussusception display abnormalities of the ENS and of estrogen receptors β.     

Ex vivo evaluation of prolidase loaded chitosan nanoparticles for the enzyme replacement therapy.

Prolidase loaded chitosan nanoparticles were set up in order to suggest an innovative therapeutic approach for Prolidase Deficiency (PD), a rare autosomal inherited disorder of the connective tissue. The satisfactory drug loading efficiency (42.6+/-2.1%) as well as the suitable physical characteristics (mean diameter of 365.5+/-35.1nm and a positive zeta-potential of 17.94+/-0.12mV) was achieved. In order to verify the compatibility of the chitosan nanoparticles with cells, the influence of the nanoparticles on the growth and the viability (MTT assay) of cultured skin fibroblasts were determined: the nanoparticles showed a good biocompatibility up to 5mug of chitosan/10,000 fibroblasts. Uptake of chitosan nanoparticles by fibroblasts was verified by confocal microscopy using FITC-labelled chitosan nanoparticles. The ex vivo experiments were performed by incubating different amounts of prolidase loaded chitosan nanoparticles with skin human fibroblasts from PD patients for scheduled times. The restored prolidase activity was quantitatively monitored by a capillary electrophoretic method and confirmed by cells morphological observations. Standing from the nanoparticles internalization, the enzymatic activity was progressively restored reaching the best value (about 66%) after 5 days of co-incubation. Moreover, prolidase loaded chitosan nanoparticles permitted to restore prolidase activity in PD fibroblasts for a prolonged period of time (8 days).     

Prenatal diagnosis of metabolic diseases on chorionic villi obtained before the ninth week of pregnancy.

Nine pregnancies at risk for various metabolic disorders were monitored by prenatal diagnosis on chorionic villi obtained between the sixth and ninth weeks of pregnancy. A diagnosis of an affected fetus was made in five cases (Sandhoff, Tay-Sachs (2), Pompe's, GM1), while metachromatic leukodystrophy, GM1 (2), and Pompe's were excluded in four cases. It is concluded that chorionic villi are a reliable tissue for prenatal diagnosis of metabolic disorders also when obtained before the ninth week.     

Minimally invasive video-assisted thyroidectomy for papillary carcinoma: a prospective study of its completeness

BACKGROUND: The effectiveness of minimally invasive video-assisted thyroidectomy (MIVAT) in papillary thyroid carcinoma is still debated. Some are concerned about this procedure in patients with thyroid cancer. This prospective study aimed to demonstrate that near-total thyroidectomy can be performed by MIVAT with similar results compared with open thyroidectomy. METHODS: A total of 33 patients with a thyroid nodule proven to be a papillary thyroid carcinoma underwent a near-total thyroidectomy. They were randomly assigned to group A (n = 16) or group B (n = 17) who were treated either by MIVAT or conventional near-total thyroidectomy, respectively. Iodine-131 thyroid bed uptake and serum thyroglobulin were measured 1 month after operation. Data were analyzed by unpaired t test and Mann-Whitney statistic methods. RESULTS: . Mean iodine-131 uptake was 5.1 +/- 4.9% in group A and 4.6 +/- 6.7% in group B. Mean thyroglobulin serum levels were 5.3 +/- 5.8 ng/mL in group A and 7.6 +/- 21.7 ng/mL in group B. The differences were not statistically significant. CONCLUSIONS: The results of this study showed that the completeness obtained with MIVAT is similar to that obtained with open thyroidectomy, with the great advantage of a minimal neck wound. No conclusions can be drawn in terms of influence of MIVAT on the outcome of the patients with small papillary thyroid carcinoma.     

A large sustained Ca2+ elevation occurs in unstimulated spines during the LTP pairing protocol but does not change synaptic strength

Synapses in the CA1 region of the hippocampus undergo bidirectional synaptic modification in response to different patterns of activity. Postsynaptic Ca2+ elevation can trigger either synaptic strengthening or weakening, depending on the properties of the local Ca2+ signal. During the pairing protocol for long-term potentiation (LTP) induction, the cell is depolarized under voltage-clamp and is given low-frequency synaptic stimulation. As an initial step toward understanding the Ca2+ dynamics during this process, we used confocal microscopy to study the Ca2+ signals in spines evoked by the depolarization itself. This depolarization activates voltage-dependent Ca2+ channels (VDCC), but whether these channels inactivate rapidly or remain functional throughout the long depolarizations used in the pairing protocol remains unknown. Cells were depolarized to 0 mV for 2-3 min. This depolarization led to a large initial elevation of Ca2+ in spines that never decayed back to resting levels. The maintained signal was close to the Kd of the low-affinity (5 microM) Ca2+ dye, Magnesium Green. We attempted to determine the functional role of this elevation, using the Ca2+-channel blocker D-890. The addition of D-890 in the internal solution produced a nearly complete abolition of the Ca2+ elevation during depolarization. Under these conditions, the NMDA conductance was normal, but LTP was almost completely blocked. This might suggest the importance of VDCC in LTP; however, we found that high concentrations of D-890 can directly inhibit calmodulin protein kinase II (CaMKII), an enzyme required for LTP induction. Thus, whereas D-890 is a useful tool for blocking postsynaptic VDCC, it cannot be used to study the contribution of these channels to plasticity. We conclude that the activation of VDCC produces a large and persistent elevation of Ca2+ in all spines, but does not produce either LTP or long-term depression (LTD) in the absence of synaptic stimulation. The possible reasons for this are discussed.     

Intrathecal chemotherapy in carcinomatous meningitis from breast cancer

Meningeal metastases occur in 2-3% of patients with breast cancer, leading to neurological morbidity and increased mortality. The criteria for treatment choice are controversial and intrathecal chemotherapy (ITC) has no documented role in the management of this disorder. We therefore evaluated the efficacy of an ITC regimen for patients presenting with carcinomatous meningitis from breast cancer. PATIENTS AND METHODS: Patients with meningeal carcinomatosis with or without concomitant parenchymal brain metastasis, were treated with repeated courses of intrathecal chemotherapy according to the following alternated weekly schedule: Day 1: Thiotepa 10 mg, methotrexate 15 mg, hydrocortisone 30 mg; Day 5: cytarabine (Ara-C) 70 mg, methotrexate 15 mg, hydrocortisone 30 mg. Folinic acid 15 mg was given orally, every six hours after methotrexate on days 2-3 and 6-7. RESULTS: Thirteen consecutive patients were treated. The median age was 45 (range 30-67) years. Eleven patients had performance status (PS) 2-3. Nine patients had other metastatic sites; synchronous parenchymal brain metastasis were present in 5 patients. Concomitant systemic chemotherapy was administered in 5 patients and external whole brain radiotherapy in 7 patients. With 12 evaluable patients we observed no responses or improvement in symptoms. Side-effects were minimal. CONCLUSION: In our series of patients, ITC failed to provide objective response or relief in clinical symptoms. Despite evidence reported in the literature indicating symptomatic improvement after ITC in a number of patients with leptomeningeal metastasis, the results of our study confirm the controversial role of ITC. New drugs and new modalities of treatment should be studied in order to efficiently control meningeal involvement of breast cancer.     

Effects of age on the urinary excretion of total and non-dialyzable hydroxyproline

Summary This study was carried out in order to investigate the effects of age on the urinary excretion of total and non-dialyzable hydroxyproline (OHPr) in normal subjects. We found that total urinary OHPr was negatively correlated with age but, by means of partial regression analysis, no correlation was found after correction for changes in creatinine clearance; on the contrary, non-dialyzable OHPr showed a statistically significant negative correlation with age (r=−0.56) even when creatinine clearance was held constant (p<0.05). A highly significant direct correlation was found between total and non-dialyzable OHPr in the whole group (r=0.54) and when only premenopausal women and men under 60 years of age were considered (r=0.51). No correlation was found when postmenopausal women and men more than 60 year-old were taken into account. Our data appear to indicate that also the decrease in osteogenetic activity is responsible for the physiological late involutional bone loss; they also show the importance of hormonal changes in inducing an uncoupling between bone formation and resorption. This work was supported by a grant from theConsiglia Nazionale delle Ricerche (CNR), Roma, Italy     

High rate of recurrence in renal transplant recipients after a first episode of venous thromboembolism

BACKGROUND: No data are available about the optimal duration of oral anticoagulant therapy (OAT) after an episode of venous thromboembolism (VTE) occurring in renal transplant (RT) recipients. Our study was undertaken to evaluate the risk of VTE recurrence in patients developing a first episode of VTE after RT. METHODS: Among 484 RT patients, 34 (7%) developed a first VTE: 28/34 VTE patients (Group 1) were prospectively studied, after stopping OAT. Group 1 was compared with a group of 84 patients without history of renal disease who had suffered from a first episode of VTE matched for age, sex and type of thrombotic event (Group 2) and with a matched group of 84 RT recipients with no history of VTE (Group 3). After OAT withdrawal, blood samples were obtained for thrombophilia and clotting activation markers (prothrombin fragment 1+2 (F1+2) and D-dimer plasma levels). RESULTS: During follow-up, 14/28 patients of Group 1 and 8/84 patients of Group 2 experienced VTE recurrence (P < 0.0005). Homocysteine, F1+2 and D-dimer plasma levels were significantly higher in Group 1 than in Group 2 and 3 (P < 0.0001 and <0.05 respectively) for all the three parameters. CONCLUSIONS: Our data outline the high risk of VTE recurrence in RT recipients. Strategies for VTE recurrence prevention are needed; Prolonged OAT, in spite of the high bleeding risk of RT patients, should be considered in this respect.