Role of the extracellular matrix in variations of invasive pathways in lung cancers

Among the most common features of highly invasive tumors, such as lung adenocarcinomas (AD) and squamous cell carcinomas (SqCC), is the massive degradation of the extracellular matrix. The remarkable qualitative and quantitative modifications of hyaluronidases (HAases), hyaluronan synthases (HAS), E-cadherin adhesion molecules, and the transforming growth factor β (TGF-β) may favor invasion, cellular motility, and proliferation. We examined HAase proteins (Hyal), HAS, E-cadherin, and TGF-β profiles in lung AD subtypes and SqCC obtained from smokers and non-smokers. Fifty-six patients, median age 64 years, who underwent lobectomy for AD (N = 31) and SqCC (N = 25) were included in the study. HAS-1, -2 and -3, and Hyal-1 and -3 were significantly more expressed by tumor cells than normal and stroma cells (P < 0.01). When stratified according to histologic types, HAS-3 and Hyal-1 immunoreactivity was significantly increased in tumor cells of AD (P = 0.01) and stroma of SqCC (P = 0.002), respectively. Tobacco history in patients with AD was significantly associated with increased HAS-3 immunoreactivity in tumor cells (P < 0.01). Stroma cells of SqCC from non-smokers presented a significant association with HAS-3 (P < 0.01). Hyal, HAS, E-cadherin, and TGF-β modulate a different tumor-induced invasive pathway in lung AD subgroups and SqCC. HAases in resected AD and SqCC were strongly related to the prognosis. Therefore, our findings suggest that strategies aimed at preventing high HAS-3 and Hyal-1 synthesis, or local responses to low TGF-β and E-cadherin, may have a greater impact in lung cancer prognosis.     

First report and molecular characterization of hepatitis E virus infection in renal transplant recipients in Brazil

Hepatitis E virus (HEV) causes acute and chronic hepatitis in organ transplant recipients. Serological evidence for HEV infection has been discovered in various population groups in Brazil, and a single acute case has been confirmed. To date, however, no cases of HEV infection in immunocompromised patients have been reported in Brazil. This study aimed to identify and characterize hepatitis E cases in renal transplant recipients in Brazil. A retrospective study was performed on 96 serum samples from renal transplant recipients with unexplained liver enzymes elevation. Three confirmed cases of HEV infection were identified that lacked seroconversion to HEV IgG antibodies. The prevalence of HEV in these patients was 3.1%. Using a sequence analysis of a 304‐nucleotide fragment within ORF2, the strains were classified as genotype 3 with a low percent identity to previously characterized strains. This is the first report of hepatitis E infection in renal transplant recipients in Brazil, and the data indicate that a novel genotype 3 subvariant may be present and that further investigation is necessary to characterize the circulating HEV strains. In this setting, HEV infection should be considered as a potential cause of abnormal liver tests of unknown origin. J. Med. Virol. 85:615–619, 2013. © 2013 Wiley Periodicals, Inc.     

Treatment with Low Doses of Polyclonal Immunoglobulin Improves B Cell Function During Immune Reconstitution in a Murine Model

Propose

After autologous stem cell transplantation (ASCT) the immunological B cell compartment recovers slowly. Delays on the recovery of B cell function after autologous stem cell transplantation are due to the low lymphocytes count and to their intrinsic dysfunction.

Methods

We studied the in vivo B cell reconstitution after ASCT examining the independent effect of polyclonal IgG (PolyIg), Fab or Fc fragments infusions in a murine animal model during a period of 12 weeks. These molecules were used in low doses, mimicking the recommended use of IVIg in the case of hypogammaglobulinemia in humans. Flow cytometry analysis and ELISA tests were conducted to monitor the reconstitution of B cells and serum immunoglobulin production. Panama blot and PCA factor 1 analysis were used to study the kinetics of immunoglobulin repertoires reconstitution. Mechanistic studies were also performed using in vitro cell culture.

Results

During follow-up after ASCT, peripheral B cells expand independently of treatment, correcting the immediate increase in sBAFF (soluble B cell activating factor) induced by previous intense myeloablation. Treatments with Fab and Fc fragments infusions promote significant IgM and IgG production comparing to control. Although the complete recovery of antibody repertoire is only achieved at the end of follow-up after ASCT, there is an earlier and significantly stronger recovery in the treated mice, which is evident at 9 weeks after ASCT. At 30 weeks after ASCT, normal values of antibody repertoire were detected in all individuals. Mechanistic studies show that Fab and Fc fragments promote IgG1 production by indirect pathways.

Conclusions

The results presented here demonstrate that polyclonal immunoglobulin indirectly improves the function of the reconstituted B cells and their IgG production by means of Fc-mediated effects on bystander cells. These results further stimulate the discussion about the advantages of IVIg therapy during immune reconstitution after human ASCT.     

Ventricular remodeling in growing rats with experimental diabetes: The impact of swimming training

Diabetic cardiomyopathy is associated with cardiac muscle remodeling, resulting in myocardial dysfunction, whereas exercise training (ET) is a useful nonpharmacological strategy for the therapy of cardiac diseases. This study tested the effects of low-intensity swimming-training on the structural remodeling of the left ventricle (LV) in growing rats with unmanaged experimental diabetes. Thirty-day-old male Wistar rats were divided into four groups (n = 5/group): sedentary-control (SC), exercised-control (EC), sedentary-diabetic (SD), and exercised-diabetic (ED). Swimming-training rats exercised 5 days/week, 90 min/day, with a load of 5% BW during 8 weeks. Sections of LV were stained with Periodic acid-Schiff, Sirius Red, and Gomori's reticulin. Seven days and 8 weeks after streptozotocin (STZ) induction (60 mg kg⁻¹ BW), blood glucose (BG) in the diabetic groups (SD = 581.40 ± 40.48; ED = 558.00 ± 48.89) was greater (p < 0.05) than in their controls (SC = 88.80 ± 21.70; EC = 85.60 ± 11.55). Swimming-training reduced BG by 23 mg/dL in the diabetics (p > 0.05). The LV of diabetic rats had increased interstitial collagen and reticular fibers on the extracellular matrix and presented glycogen accumulation. More importantly, all these adverse tissue changes induced by STZ were attenuated by ET. Together, these findings support the idea of a beneficial role of exercise in the LV remodeling in rats with unmanaged type-1 diabetes mellitus.     

A phylogenetic analysis using multidirectional chromosome painting of three species (Uroderma magnirostrum, U. bilobatum and Artibeus obscurus) of subfamily Stenodermatinae (Chiroptera-Phyllostomidae)

The species of genera Uroderma and Artibeus are medium-sized bats belonging to the family Phyllostomidae and subfamily Stenodermatinae (Mammalia, Chiroptera) from South America. They have a wide distribution in the Neotropical region, with two currently recognized species in Uroderma and approximately 20 species in Artibeus. These two genera have different rates of chromosome evolution, with Artibeus probably having retained the ancestral karyotype for the subfamily. We used whole chromosome paint probe sets from Carollia brevicauda and Phyllostomus hastatus on Uroderma magnirostrum, Uroderma bilobatum, and Artibeus obscurus. With the aim of testing the previous phylogenies of these bats using cytogenetics, we compared these results with published painting maps on Phyllostomidae. The genome-wide comparative maps based on chromosome painting and chromosome banding reveal the chromosome forms that characterize each taxonomic level within the Phyllostomidae and show the chromosome evolution of this family. Based on this, we are able to suggest an ancestral karyotype for Phyllostomidae. Our cladistic analysis is an independent confirmation using multidirectional chromosome painting of the previous Phyllostomidae phylogenies.     

Comparative analysis of routine parasitological methods for recovery of cysts,molecular detection,and genotyping of Giardia duodenalis

European Journal of Clinical Microbiology & Infectious Diseases - In order to improve the diagnosis of giardiasis, fecal samples (high/medium/low concentration of cysts) were processed by the...     

Evolution of endodontic medicine: a critical narrative review of the interrelationship between endodontics and systemic pathological conditions

Odontology - Endodontics has gained emphasis in the scientific community in recent years due to the increase in clinical and in animal models studies focused on endodontic medicine, which aims to...     

Survival and prognostic factors in patients with oral squamous cell carcinoma

Background This study aimed to evaluate sociodemographic and clinical factors influencing overall survival (OS) in patients with oral squamous cell carcinoma (OSCC). Material and Methods Medical charts of 547 patients with OSCC from a public hospital in northeastern Brazil seen between 1999 and 2013 were evaluated. Survival analysis was performed using the Kaplan-Meier method. The influence of age, sex, ethnicity, clinical stage, anatomical location, type of treatment, and comorbidities on the patients’ prognosis was evaluated. Cox proportional hazards regression model was used to identify independent prognostic factors. Results The 5-year OS was 39%. Multivariate analysis showed that age < 40 years (HR = 2.20; 95%CI: 1.02-4.72) and a single treatment modality (HR = 1.91; 95%CI: 1.37-2.67) were associated with a poor prognosis, while early clinical stage resulted in better outcomes (HR = 0.38; 95%CI: 0.25-0.58). Conclusions OSCC patients in advanced clinical stages, diagnosed at a younger age, and submitted to a single therapeutic modality have a poorer prognosis. Key words:Head and neck cancer, oral cancer, oral squamous cell carcinoma, survival, prognosis.     

Selective,stepwise, or nonselective removal of carious tissue: which technique offers lower risk for the treatment of dental caries in permanent teeth? A systematic review and meta-analysis

This study aimed to systematically review the literature regarding the risk of selective removal—in comparison with stepwise and nonselective removal     

Diode laser surgery versus electrocautery in the treatment of inflammatory fibrous hyperplasia: a randomized double-blind clinical trial

Objectives

To compare the efficacy and safety of diode laser and electrocautery techniques for inflammatory fibrous hyperplasia (IFH) removal.

Materials and methods

In this randomized double-blind clinical trial, 40 individuals were randomly allocated to two groups: group 1 (G1) consisted of 20 individuals assigned to treatment with diode laser and group 2 (G2) consisted of 20 individuals assigned to treatment with electrocautery. The following transoperative parameters were evaluated: bleeding, temperature, and surgical technique parameters (energy deposited on tissue, flow rate, and time of incision). The postoperative parameters evaluated were as follows: pain, functional alterations (chewing, speaking), analgesic medication intake, swelling, healing of the wound area, and patient satisfaction.

Results

Among the 40 individuals included in the study, four (two in G1 and two in G2) did not complete the entire follow-up. Therefore, 36 individuals (18 in G1 and 18 in G2) participated. Participants in G1 and in G2 had similar demographic characteristics. No difference regarding the trans- or postoperative parameters evaluated was observed between G1 and G2 (p > 0.05). Also, no difference regarding the time for healing was observed between groups.

Conclusions

Diode laser seems to be as effective and safe as electrocautery when applied under similar conditions for IFH removal.

Clinical relevance

IFH corresponds to 65% of the lesions observed in denture wearers. This study shows that under similar conditions diode laser is as effective and safe as electrocautery for removal of IFH.