Risk of lymph node metastases in multifocal papillary thyroid cancer associated with Hashimoto's thyroiditis

AIMS: The aim of this study was to evaluate the risk factors of lymph nodes metastases (LNM) in patients with papillary thyroid cancer (PTC) and coexisting Hashimoto’s thyroiditis (HT). PATIENTS AND METHODS: This was a retrospective cohort study of patients with PTC and HT who had undergone total thyroidectomy (TT) with central neck dissection (CND) over an 11-year period (between 2002 and 2012). Pathological reports of all eligible patients were reviewed. Multivariable analysis was performed to identify risk factors of LNM. RESULTS: During the study period, PTC was diagnosed in 130 patients with HT who had undergone TT with CND (F/M ratio = 110:20; median age, 52.4 ± 12.7 years). Multifocal lesions were observed in 28 (21.5 %) patients. LNM were identified in 25 of 28 (89.3 %) patients with multifocal PTC and HT versus 69 of 102 (67.5 %) patients with a solitary focus of PTC and HT (p = 0.023). In multivariable analysis, multifocal disease was identified as an independent risk factor for LNM (odds ratio, 3.99; 95 % confidence interval, 1.12 to 14.15; p = 0.033). CONCLUSIONS: Multifocal PTC in patients with HT is associated with an increased risk of LNM. Nevertheless, the clinical importance of this finding needs to be validated in well-designed prospective studies

Indometacin loading and in vitro release properties from novel carbopol coated spherical mesoporous silica nanoparticles

Spherical MCM-41 silica nanosized particles were synthesized and post synthesis modified by 3-aminopropyltriethoxysilane (APTES) in order to prepare amino-functionalized carrier. Both types of silica particleswere loaded with indometacin and further coated with carbopol. The preservation of morphology and pore structure of the particles was observed by XRD, TEM and N2 physisorption. FT-IR spectroscopy revealed the interaction between carboxyl groups of indometacin and the amino groups of the functionalized MCM-41. Amino-functionalization of the carrier resulted in higher degree of indometacin loading in comparison to the parent MCM-41, 39% vs. 30%, respectively. The coating of drug loaded amino-MCM-41 silica particles with carbopol significantly reduced the initial burst release of indometacin. Both silica carriers demonstrated no cytotoxicity on HL-60 (acute myeloid leukemia) and K-562 (chronic myeloid leukemia) cell lines

The Role of Bile in the Regulation of Exocrine Pancreatic Secretion

As early as 1926 Mellanby (1) was able to show that introduction of bile into the duodenum of anesthetized cats produces a copious flow of pancreatic juice. In conscious dogs, Ivy & Lueth (2) reported, bile is only a weak stimulant of pancreatic secretion. Diversion of bile from the duodenum, however, did not influence pancreatic volume secretion stimulated by a meal (3,4). Moreover, Thomas & Crider (5) observed that bile not only failed to stimulate the secretion of pancreatic juice but also abolished the pancreatic response to intraduodenally administered peptone or soap

Aging Hematopoiesis: Functional Insights and Prospects for Rejuvenation

Aging exerts profound effects on the hematopoietic system, leading to a loss of homeostatic control and reduced regenerative capacity. Clinical consequences of these changes include anemia, compromised immune function and an increased prevalence of myeloid disorders among the elderlies. A growing body of evidence suggests that defects at the stem and progenitor cell levels contribute to many of the hematopoietic aging phenotypes. In this thesis, I examined the function of hematopoietic stem cells (HSCs), the source of all mature blood cells, during adulthood and upon aging. By using an in vivo lineage tracing mouse system and high-throughput RNA profiling, I demonstrate a gradual decline in HSC multilineage differentiation capacity, with the most significant reduction in their lymphoid output. Decreased lymphopoiesis could be traced back to the primitive lymphoid progenitor subset, MPP Ly-I, revealing defects in the transition of HSC to these cells. To address age-related HSC decline, we employed a recently developed HSC culture system which allows for activation and robust self-renewal of input HSCs. Although ex vivo culture of aged HSCs failed to correct their in vivo function, we nevertheless observed that the aged HSC pool contains rare multilineage/lymphoid competent clones, which makes these promising candidates for strategies aimed at hematopoietic rejuvenation. In parallel, we investigated molecular changes associated with age-related HSC decline by re-analyzing existing transcriptomic data on HSC aging. We discovered only partial overlap in HSC aging signatures between prior studies, which prompted us to address the potential causes for such variation. We found that cell isolation procedure and sample handling both impact on the molecular profiles of the cells. In particular, incubation of cells at elevated temperature triggered a stress signature which overrides the genuine molecular profile of the cells. Notably, this stress response was age-independent, but with implications for prior interpretations of HSC aging mechanisms. Finally, given the intrinsic nature of many of the age-associated HSC phenotypes, we explored the potential for cell replacement therapy through young HSC transplantation to reinstate a more youthful hematopoietic function in older subjects. While several key parameters needed to be optimized, including non-invasive conditioning regimen prior to transplantation and HSC transplant doses, we demonstrated successful integration of young HSCs in aged recipients. Importantly, these young cells largely retained their function in the aged environment, contributing effectively to hematopoietic output, and particularly to mature lymphocytes. Hence, this data suggest that non-invasive transplantation of young HSCs holds promise as a potential strategy to alleviate some hematopoietic aging phenotypes. Collectively, this thesis work provides new insights into hematopoietic aging and set the stage for more comprehensive investigations of HSC transplantation as a potential approach for hematopoietic rejuvenation