High-magnitude mechanical strain inhibits the differentiation of bone-forming rat calvarial progenitor cells

Purpose: Orthodontic tooth movement occurs during the bone remodeling induced by therapeutic mechanical strain. It is important to investigate the relation between the strength of mechanical stress and bone formation activity. The aim of this study was to determine the effect of high-magnitude mechanical strain on bone formation in detail.

Materials and methods: Osteoblast-like cells isolated from fetal rat calvariae were loaded with 18% cyclic tension force (TF) for 48?h. To phenotypically investigate the effect of TF, we measured the number and the size of bone nodules stained by von Kossa technique on day 21 after cell seeding and determined the calcium content of bone nodules on day 14. Furthermore, we examined the gene expression of BMP-2, Runx2 and Msx2, which are important factors for bone nodule formation, on days 1, 4 and 7 after TF loading.

Results: The maximum bone nodule size in the control group was 1620 and 719?μm in the TF group. Furthermore, the mean number of bone nodules sized over 360?μm in the TF group was significantly decreased compared to the control group. The calcium content was also significantly decreased to 42% by TF loading. The mRNA expression of BMP-2, Runx2 and Msx2 was decreased 1 and 4 days after TF loading.

Conclusion: The differentiation of bone forming progenitor cells into bone nodule forming cells was inhibited by TF due to the decreased expression of bone formation related factors such as BMP-2, Runx2 and Msx2.     

The Neurosteroid Allopregnanolone Is Reduced in Prefrontal Cortex in Alzheimer’s Disease

BACKGROUND: Few data are currently available investigating neurosteroids (NS) in Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and plasma in patients with AD, but it is unclear if allopregnanolone is also reduced in brain. Because a number of NS exhibit neuroprotective effects and impact cognitive performance in rodent models, these molecules may be relevant to the pathophysiology of neurodegenerative disorders. We therefore investigated prefrontal cortex (PFC) NS levels in AD. METHODS: Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male control subjects by gas chromatography/mass spectrometry preceded by high-performance liquid chromatography purification. RESULTS: Subjects with AD exhibit significant reductions in allopregnanolone compared with cognitively intact control subjects (median levels = 2.50 ng/g vs. 5.59 ng/g, respectively; p = .02). Allopregnanolone levels are inversely correlated with neuropathological disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in subjects with AD (p = .01). CONCLUSIONS: Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD.     

Neuroendocrine factors regulating blood glucose, plasma FFA and insulin in the development of obesity

A number of neurotransmitters and neuropeptides in the hypothalamus play a role in the control of food intake, metabolism, and body weight. Particularly, noradrenergic mechanisms in several areas of the hypothalamus are involved. Control of peripheral metabolism by the hypothalamus is achieved via autonomic modulation of the function of hepatocytes, adipocytes, and the endocrine cells in the islets of Langerhans. The autonomic control mechanisms ultimately lead to an appropriate shaping of blood glucose, plasma FFA, and insulin profiles to guarantee an adequate flow of nutrients under different physiological situations. Peripheral insulin and glucose can penetrate into the brain where they might affect the function of those brain structures involved in control of food intake, metabolism, and body weight.     

Pulmonary metastases from epithelial tumours: late results of surgical treatment.

OBJECTIVE: Development of distant metastases is one of the primary characteristics of malignant tumours. During the last decades, lung metastasectomy has been progressively accepted as a therapeutic option in oncology patients. The present paper aims to evaluate the long-term results and factors influencing prognosis in patients submitted to lung resection for metastases from extrapulmonary epithelial tumours. METHODS: We retrospectively analysed data of 202 patients undergoing 207 procedures of lung metastasectomy between January 1980 and December 2003. Factors that may influence long-term prognosis such as completeness of resection, histology of the tumour, disease-free interval, number of resected lesions, involvement of hilar or mediastinal lymph nodes, systemic treatments were investigated. RESULTS: Complete resection was carried out in 169 patients (83.7%). The more frequent lung resection was sublobar in 67.6% of cases, but rarely in selected patients bilobectomy or pneumonectomy has been carried out too. Perioperative morbidity and mortality were 7.7% and 0.9%. Mean disease-free interval was 49+/-48 months. Mean follow-up was 33+/-31 months, 5-year and 10-year survival rates for completely resected patients were 43% and 17%, respectively. By univariate and multivariate analyses, completeness of resection, disease-free interval of 36 months or more, and single resected metastasis were found to be significant prognostic factors. CONCLUSIONS: Resection of epithelial lung metastases allows an acceptable prognostic result in appropriately selected patients with very low perioperative morbidity and mortality. Factors such as high disease-free interval, single metastasis and completeness of resection are demonstrated and confirmed to be significantly associated with long-term survival.     

Ethanol:water mutually enhanced transdermal therapeutic system. I: Nitroglycerin solution properties and membrane transport

The solution properties of aqueous ethanol donor solutions were characterized for the particular case of an increased flux nitroglycerin transdermal system. Permeation through porous and nonporous polymer membranes was investigated and modelled. While the permeation of ethanol through the porous membranes is adequately described by theory, clogging of pores occurs in the presence of lactose. Permeation through ethylene vinyl acetate membranes reflects interactions of the solute and solvent with the polymer.     

Hepatitis C virus outside the liver

Observational and some experimental data suggest that hepatitis C virus can manifest in a variety of disease processes outside the liver. The links between hepatitis C virus and membranoproliferative glomerulonephropathy, porphyria cutanea tarda, lichen planus, cryoglobulinemia, diabetes mellitus, B-cell non-Hodgkin’s lymphoma, and thyroiditis are critically reviewed. Based on the available evidence, recommendations for the clinical approach to patients with extrahepatic diseases are discussed.     

Renin-producing renal cell carcinomas—clinical and experimental investigations on a special form of renal hypertension

Summary The pathogenetic relationship between tumour and hypertension was investigated in 129 patients with renal cell carcinoma, of whom 41 (31.8%) were hypertensive. Of these 41 patients with renal tumours and hypertension, 6 (14.6%) were found to have primary reninism. In these patients the plasma renin activity in blood from the renal veins showed a tumour kidney to contralateral kidney ratio of between 4 and 7, and 2 patients also had secondary hyperaldosteronism. In the same 6 cases the renin content in the renal tumour tissue was significantly higher than that in tissue from the adjacent tumour-free renal cortex of the ipsilateral kidney. Immunohistochemical demonstration of renin in the tumour was only possible in these 6 cases. In 5 of these patients blood pressure returned to normal following nephrectomy; in the 6th case there was a drop in blood pressure after nephrectomy. In 3 renin-positive tumours examined, autonomous renin production was demonstrated in cell culture. Renin-producing renal cell carcinomas are an uncommon cause of renal hypertension. The differential diagnosis of hypertension should therefore also include renal tumour.