Post–conditioning reduces infarct size in the isolated rat heart: Role of coronary flow and pressure and the nitric oxide/cGMP pathway

We aimed to assess the role of the nitric oxide (NO)–cGMP pathway in cardioprotection by brief intermittent ischemias at the onset of reperfusion (i.e., post–conditioning (Post–con)). We also evaluated the role of coronary flow and pressure in Post–con. Rat isolated hearts perfused at constant– flow or –pressure underwent 30 min global ischemia and 120 min reperfusion. Post–con obtained with brief ischemias of different duration (modified, MPost–con) was compared with Post–con obtained with ischemias of identical duration (classical, C–Post–con) and with ischemic preconditioning (IP). Infarct size was evaluated using nitro–blue tetrazolium staining and lactate dehydrogenase (LDH) release. In the groups, NO synthase (NOS) or guanylyl–cyclase (GC) was inhibited with LNAME and ODQ, respectively. In the subgroups, the enzyme immunoassay technique was used to quantify cGMP release. In the constant–flow model, M–Post–con and C–Post–con were equally effective, but more effective than IP in reducing infarct size. The cardioprotection by M–Post–con was only blunted by the NOS–inhibitor, but was abolished by the GC–antagonist. Post–ischemic cGMP release was enhanced by MPost–con. In the constant–pressure model IP, M–Post–con and C–Post–con were equally effective in reducing infarct size. Post–con protocols were more effective in the constant–flow than in the constant–pressure model. In all groups, LDH release during reperfusion was proportional to infarct size. In conclusion, Post–con depends upon GC activation, which can be achieved by NOS–dependent and NOS–independent pathways. The benefits of M– and CPost–con are similar. However, protection by Post–con is greater in the constant–flow than in the constant–pressure model.     

Comparative evaluation of recombinant human thyrotropin-stimulated thyroglobulin levels, 131I whole-body scintigraphy, and neck ultrasonography in the follow-up of patients with papillary thyroid microcarcinoma who have not undergone radioiodine therapy

CONTEXT: Although the prognosis of papillary thyroid microcarcinoma (PTMC) is usually excellent, the optimal follow-up strategy has never been investigated. OBJECTIVE: The objective of the study was to investigate the role of neck ultrasonography (US), whole-body scintigraphy (WBS), and serum thyroglobulin levels (Tg) after recombinant human (rh) TSH in the follow-up of very low-risk PTMC patients. DESIGN: The study was a 5-yr observational study based on a 6- to 12-month follow-up after near total thyroidectomy. SETTING: The study population consisted of ambulatory patients. PATIENTS: Eighty consecutive patients diagnosed with PTMC, who had not undergone postoperative radioiodine treatment because of unifocal tumor without lymph node metastases and who did not have anti-Tg antibodies, were included. MAIN OUTCOME MEASURES: WBS and Tg after both rhTSH and neck US were measured. RESULTS: rhTSH-Tg was 1 ng/ml or less in 45 (Tg-) and more than 1 in 35 (Tg+) patients. WBS showed no pathological uptake in any patient. US identified node metastases in two Tg (+) and one Tg (-) patients. rhTSH-Tg levels positively correlated with thyroid bed iodine uptake (r = 0.40, P < 0.0001). To date (32 +/- 13 months after surgery), all node-negative patients have undetectable Tg levels on LT(4) treatment and negative US. CONCLUSIONS: For the initial follow-up of PTMC patients without risk factors and anti-Tg antibodies and who did not undergo radioiodine treatment: 1) WBS is useless; 2) US is highly sensitive in detecting node metastases; and 3) detectable rhTSH-Tg levels mainly depend on small normal tissue remnants. In this subgroup of PTMC patients, neck US might be regarded as a primary tool for the initial follow-up.     

Effects of Cerium Oxide Nanoparticles on PC12 Neuronal-Like Cells: Proliferation, Differentiation, and Dopamine Secretion

Purpose

Oxidative stress has been found to play a key role in several diseases, that range from cancer to neurodegenerative disorders. Besides traditional anti-oxidant agents, in recent years much attention has been focused on nanotechnological solutions, including cerium oxide nanoparticles (nanoceria).

Methods

Thanks to its extraordinary catalytic properties, nanoceria mimics the activity of superoxide dismutase and of catalase, therefore acting as a reactive oxygen species (ROS) scavenger in many biological contexts. In this paper, we report on nanoceria interactions with PC12 cell line, that represents a valuable model for many features of central dopaminergic neurons.

Results

Nanoceria confirmed a strong anti-ROS action but, most interestingly, also showed beneficial effects on both cell differentiation and dopamine production.

Conclusions

Even if deeper examinations will be necessary in order to better clarify the mechanisms at the base of the documented effects, nanoceria demonstrated a significant potential as pharmacological agent in the treatment of neurological disorders.     

Spatial and temporal dynamics of innervation during the development of fetal human pancreas

The delineation of pancreatic nerve innervation during fetal life may contribute to our understanding of pancreatic pain modalities after birth. The aim of this study was to characterize the spatial and temporal distribution of nerve structures in the human pancreas throughout gestation. Computer-based image morphometry with piecewise polynomial interpolation analysis was performed to quantify nervous structures in the head, body and tail of the pancreas. Nerve structures were detected by automatic immunostaining techniques using a polyclonal antibody against two S-100 proteins that reacts strongly with human S100A and B that are detected in Schwann cells. Immunoreactivity was found in the parenchyma of head, body and tail of the pancreas with the relative density being head>body>tail. In addition to this extensive set of nerve fibers terminating in the pancreas there were large bundles of en passant nerve fibers in the dorsal region of the pancreas that were 3D reconstructed and were associated with the superior mesenteric plexus. If at first glance, the perimeter and the width of the nerve fibers seem to increase at a continuous rate up to term in all three regions of the pancreas, spatial and temporal co-analysis identified that the head of the pancreas shows a two-peak growth increase at 14 and 22 weeks of gestation with regard to the area, perimeter and width of the nerve structures, while the body and tail regions show a unique peak at 20 weeks. A developmental deceleration was found between the 22nd and the 36th week of gestation for the head region only. This is the first systematic study of nerve innervation of the human pancreas throughout gestation. The developmental dynamics of the pancreas nerve innervation corresponds approximately to the remodeling of the intrahepatic biliary system. Understanding the factors and disease states that may alter the distribution of nerve structures can be of significance for the development of therapies in pancreatic disorders of child- and adulthood.     

Induction of resistance to Schistosoma mansoni by immunization with subfractions of worms

Induction of resistance to a Schistosoma mansoni infection was analyzed following injections of glutaraldehyde-fixed parasites or of subfractions prepared from nonfixed parasites killed by repeated freeze-thaw cycles. The parasites were isolated from mice infected 4 weeks previously and the subfractions were prepared by extraction in buffered saline or in detergent. A variety of immunization protocols were conducted in rats and mice. These included different sites of injection, dose size, and number of booster injections; different adjuvants; and the effects of boosting with live infections. Induction of a partial resistance is observed in rats, but has not been achieved in mice immunized by the same procedures. The alum-precipitated detergent-solubilized fraction was superior at lower doses. Exposure of rats to a low dose cercarial infection 3 weeks prior to challenge did not boost the resistance if the rats were already partially resistant through vaccination with worm subfractions in adjuvant. Serum from vaccinated rats transfers partial protection to a challenge infection of naive rats.     

Non-communicable chronic diseases and timely breast cancer screening among women of the Eastern Caribbean Health Outcomes Research Network (ECHORN) Cohort Study

Purpose

The Caribbean population faces a growing burden of multiple non-communicable chronic diseases (NCDs). Breast cancer is the leading cause of cancer death for women in the Caribbean. Given the substantial burden of NCDs across the region, cancer prevention and control strategies may need to be specifically tailored for people with multiple co-morbidities. Preventive screening, such as timely mammography, is essential but may be either facilitated or hampered by chronic disease control. The main objective of this study is to examine the relationship between a chronic disease and timely breast cancer screening.

Methods

We conducted a cross-sectional data analysis using baseline data from the Eastern Caribbean Health Outcomes Research Network (ECHORN) Cohort Study—ECS. Our independent variables were presence of chronic diseases (hypertension or diabetes), defined as having been told by a clinical provider. Our dependent variable was timely screening mammography, as defined by receipt of mammography within the past 2 years. We examined bivariate and multivariate associations of covariates and timely screening mammography.

Results

In our sample (n?=?841), 52% reported timely screening mammography. Among those with timely screening, 50.8% reported having hypertension, and 22.3% reported having diabetes. In our bivariate analyses, both diabetes and hypertension were associated with timely screening mammography. In partially adjusted models, we found that women with diabetes were significantly more likely to report timely screening mammography than women without diabetes. In our fully adjusted models, the association was no longer significant. Having a usual source of healthcare and a woman’s island of residence were significantly associated with timely screening mammography (p?<?0.05).

Conclusions

We found that half of eligible women received timely screening mammography. Diabetes and hypertension, though common, are not associated with timely screening mammography. Usual source of care remains an important factor to timely breast cancer screening.

     

Prognostic factors in Sezary syndrome: A multivariate analysis of clinical, haematological and immunological features

Background: Sézary syndrome (SS) prognostic factors are not well defined because of the rarity of this disease. The specific goal of this prospective study was to assess by multivariate analysis the predictive value with respect to survival of a series of clinical, haematological and immunological parameters taken at SS diagnosis.Patients and methods: A cohort of 62 SS patients diagnosed and followed since 1975 was examined, and 51 were included in the multivariate analysis model.Results: The median survival time was 31 months (range: 1 month–15.7+ years), and the five-year survival rate 33.5%. The following variables were found by univariate analysis to be associated with a poor prognosis at the time of SS diagnosis: previous history of mycosis fungoides (P = 0.013), high number of circulating leukocytes (P = 0.001), Sézary cells (SC) (P < 0.001) and CD4+ cells (P < 0.001), presence of large circulating SC (P < 0.001), above normal range LDH serum levels (P = 0.015), presence of PAS-positive inclusions in the cytoplasm of circulating SC (P < 0.001), high CD4/CD8 ratio (P = 0.004) and a CD7 negative circulating SC phenotype (P < 0.001). Among them, the stepwise multivariate analysis selected as adverse independent prognostic factors: PAS-positive cytoplasmic inclusions (P = 0.001), CD7 negative phenotype (P = 0.018) and presence of large circulating SC (P = 0.045).Conclusions: Two low-/high-risk groups have been singled out on the basis of the risk index. Patients with no or one adverse prognostic feature(s) (risk index 1; n = 31) share a slow disease course and a relatively favorable prognosis (five-year survival: 58%); on the other hand, patients with 2 or 3 adverse prognostic features (risk index > 1; n = 20) are characterized by an aggressive disease course not modifiable by traditional therapies (five-year survival: 5%).