Neuroadrenergic denervation of the lung in type I diabetes mellitus complicated by autonomic neuropathy

STUDY OBJECTIVE: To verify whether autonomic neuropathy (AN) complicating type I, insulin-dependent diabetes mellitus affected neuroadrenergic bronchopulmonary innervation. PATIENTS: Twenty nonsmoking diabetic patients without respiratory diseases were studied: 11 patients with AN (group AN) and 9 patients without AN (control; group C) diagnosed by standardized criteria. DESIGN: Patients underwent respiratory function tests and ventilatory scintigraphies with (123)I-metaiodobenzylguanidine (MIBG) and with (99m)Tc-diethylenetriaminepenta-acetic acid (DTPA) to assess both bronchopulmonary neuroadrenergic innervation and also permeability of the alveolar-capillary barrier to water-soluble tracers. Rates of pulmonary clearance of the two tracers were computed, and correlates were identified by nonparametric statistics. SETTING: University hospital. RESULTS: The AN and C groups had normal respiratory function test results and comparable duration of diabetes and quality of metabolic control. (99m)Tc-DTPA clearance did not distinguish the groups. (123)I-MIBG clearance was faster in the AN group than in the C group (mean +/- SD half-time of the radiotracer time-activity curve [T(1/2)], 116.1 +/- 22.8 min in the AN group vs 139.5 +/- 18.3 min in the C group, p = 0.022), which is consistent with neuroadrenergic denervation in the AN group. (123)I-MIBG clearance was independent from (99m)Tc-DTPA clearance. Faster (123)I-MIBG clearance was significantly associated with worse performance in three of the four autonomic tests. CONCLUSIONS: Neuroadrenergic bronchopulmonary denervation may occur in diabetic patients with AN despite normal clinical and respiratory function findings. Further research is needed to identify clinical and prognostic implications of these findings.     

Towards curative therapy in gastric cancer:Faraway,so close!

Although recent diagnostic and therapeutic advances have substantially improved the survival of patients with gastric cancer(GC), the overall prognosis is still poor. Surgery is the only curative treatment and should be performed in experienced centers. Due to high relapse following surgery, complementary and systemic treatment aimed at eradicating micrometastasis should be performed in most cases. Cytotoxic treatments are effective in downstaging locally advanced cancer, but different sensitivities and toxicities probably exist in different GC subtypes. Current treatment protocols are based primarily on clinical data and histological features, but molecular biomarkers that would allow for the prediction of treatment responses are urgently needed. Understanding how host factors are responsible for inter-individual variability of drug response or toxicity will also contribute to the development of more effective and less toxic treatments.     

The maternal 14 bp Ins/Del polymorphism in HLA‐G is not associated with preeclampsia risk

The effect of HLA‐G 14 bp Ins/Del polymorphism (rs371194629) on the risk of preeclampsia has been assessed in several populations, yet the results are still conflicting. Lack of power due to small sample sizes is a common cause of inconsistencies in genetic association studies. We aimed to test whether the maternal polymorphism is associated with preeclampsia, eclampsia or HELLP syndrome (acronym for Hemolysis, Elevation of Liver enzymes, Low Platelets). To achieve a statistical power greater than 0.90, a total of 741 women (332 controls, 246 preeclampsia, 57 eclampsia and 106 HELLP) were genotyped for the 14‐bp Ins/Del polymorphism. The genetic association with disease status was assessed by Fisher's exact test and odds ratio (OR) estimates using logistic regression model adjusted for maternal age and parity status. Allele and genotype distributions were the same between control and case groups (p > .05). The polymorphism was not associated with the risk of developing preeclampsia [OR = 0.93 (0.72–1.19); p = .541], or eclampsia [OR = 0.90 (0.60–1.38); p = .628] nor HELLP syndrome [OR = 0.92 (0.66–1.28); p = .628]. This well‐powered study clearly demonstrates that the maternal HLA‐G 14‐bp Ins/Del polymorphism is not associated with preeclampsia risk. However, as the offspring genotypes were not evaluated here, we could not rule out the effect of the foetal genotype on the preeclampsia pathogenesis.     

Podoplanin,ezrin, and Rho-A proteins may have joint participation in tumor invasion of lip cancer

Introduction

Podoplanin and ezrin connection through Rho-A phosphorylation have been suggested as part of the activation pathway, in the process of tumor invasion and cell movement in oral squamous cell carcinomas.

Objective

The aim of this study was to evaluate the correlation among podoplanin, ezrin, and Rho-A immunoexpressions in 91 squamous cells carcinomas of the lower lip and their influence in patient’s prognosis.

Material and methods

The immunoexpressions of podoplanin, ezrin, and Rho-A were evaluated through a semi-quantitative score method, based on the capture of 10 microscopic fields at the front of tumor invasion. The association and correlation of these proteins with the clinicopathological features were verified by Fischer’s exact test and Spearman’s test. The prognostic values were analyzed by Kaplan-Meier method and log-rank test.

Results

A statistically significant association between strong cytoplasmic podoplanin expression and alcohol (p = 0.024), loco-regional recurrences (p = 0.028), and lymph node metastasis (pN+) (p = 0.010) was found. The membranous (p = 0.000 and r = 0.384) and cytoplasmic (p = 0.000 and r = 0.344) podoplanin expression was statistically correlated with ezrin expression. Also, membranous podoplanin was significantly correlated with Rho-A expression (p = 0.006 and r = 0.282). The expressions of podoplanin, ezrin, and Rho-A were not significant prognostic factors for patients with squamous cell carcinomas of the lower lip.

Conclusions

Therefore, our results confirm a correlation among podoplanin, ezrin, and Rho-A expressions in squamous cell carcinoma of the lip suggesting a cooperative participation of these proteins in cell movement and invasion.

Clinical relevance

Furthermore, strong cytoplasmic podoplanin expression could be helpful to identify patients with squamous cell carcinoma of the lip and lower risk of loco-regional recurrences.