Changes in vascularity of cartilage endplate of degenerated intervertebral discs in response to melatonin administration in rats

We carried out an experimental investigation of cartilage endplate vascularity of degenerated intervertebral discs produced by exogenous melatonin (MEL) treatment. Adult Swiss albino rats were divided into three groups: control, operated degeneration, and MEL treatment. There were five rats in each group and, using a posterior approach, cuts were made parallel to the endplates in the posterior annulus fibrosus in five consecutive intervertebral discs between the 5th and 10th vertebral segments of the rats' tails. At 8 weeks, five of these animals were treated with exogenous MEL (s.c. injection of 30 μg/100 g body weight daily for 4 weeks). In each experimental group, one animal was examined using CT scanner to study the density of the cartilage endplate of the disc. To evaluate the bone growth and vascularity of the cartilage endplate region, the animals were killed for subsequent histopathological evaluation. We found that the vascular channel counts and percentage areas from animals treated with MEL were significantly lower than from the operated degeneration animals. Accordingly, the density histogram in the MEL group showed a spike profile for both the vertebral body and the cartilage endplate, indicating an increase in the amount of higher density tissues in these regions. Our results demonstrate that the use of MEL reduces the cartilage endplate vascularity of degenerated intervertebral discs, suggesting that it may have an osteoinductive effect on bone formation. Further studies are needed to characterize fully the relevance of our findings for the treatment of disorders such as postmenopausal osteoporosis.     

Feasibility of breast conserving surgery in multifocal breast cancers

Background

Multifocal breast cancers (MFBCs) present a challenge to surgeons. Although its feasibility is still controversial, breast-conserving surgery (BCS) is not contraindicated for MFBCs. The investigators retrospectively evaluated the feasibility of BCS and reviewed histopathologic findings in patients with MFBC.

Methods

A total of 222 patients with MFBC who were treated with either BCS (119 patients) or mastectomy (103 patients) at a single institution between January 2002 and December 2011 were retrospectively evaluated.

Results

The median follow-up time was 55 months (range, 10 to 102 months). Lymphovascular invasion and lymph node involvement were significantly less frequent in the BCS group (48.8% vs 62.2% for lymphovascular invasion, P = .04; 52.1% vs 71.8% for lymph node involvement, P = .002). There were no differences in local recurrence rates between the 2 groups. The overall survival rates were 92% in the BCS group and 72% in the mastectomy group (P = .000).

Conclusions

BCS is a feasible and safe procedure for the removal of multifocal tumors. Extended lymphovascular invasion is associated with mortality in patients who undergo mastectomy.     

Metal Concentrations of Wild Edible Mushrooms from Turkey

In the present study, the contents of Zn, Fe, Cu, Mn, Co, Ni, Pb, Cd, Cr, Al, Ca, Mg, and K in Agaricus campestris, Agrocybe cylindracea, Collybia dryophila, Helvella leucopus, Russula delica, Tricholoma auratum, Amanita ovoidea, Melanoleuca excissa, Rhizopogon roseolus, Russula chloroides, Volvoriella gloiocephala, Lyophyllum decastes, Morcella angusticeps, Morchella esculenta and Morcella eximia collected from Isparta, Mugla, and Osmaniye provinces (Turkey) were determined by inductively coupled plasma optical emission spectrometry (ICP-OES) after microwave digestion. The intake of heavy metals (Pb, Cd) and other metals (Fe, Cu, Zn) by consumption of 30 g dry weight of mushrooms daily poses no risk at all except in A. cylindracea and H. leucopus (for Cd) for the consumer.     

The effects of cyclosporine on antioxidant enzyme activities and malondialdehyde levels in rabbit hepatic tissues

Possible molecular mechanisms leading to cyclosporine-induced hepatotoxicity has not been cleared yet. Therefore, investigation of antioxidant status of hepatic tissues exposed to cyclosporine A (CsA) and of free radical involvement in the CsA-induced hepatotoxicity seems of importance. For this aim, 20 rabbits were used in the study. In each group (control, CsA, CsA plus vitamin and, vitamin only) there were 5 animals. CsA was given orally (25 mg/kg/day) for 10 days. Vitamins E (100 mg/kg/ day) and C (200 mg/kg/day) combination was injected intramuscularly. After 10th day, animals were killed, and livers were prepared for the enzymatic assays. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) and, malondialdehyde (MDA) levels were determined in the supernatant fractions. Lowered SOD, unchanged GSH-Px and, increased CAT activities and MDA levels were detected in hepatic tissues of rabbits treated with CsA as compared with controls. In the CsA plus vitamin group, SOD activity was found to be higher, GSH-Px and CAT activities unchanged and MDA levels lower than the CsA group. In the vitamin-treated group, all of the enzyme activities were higher than the controls but MDA levels were unchanged. Correlation analysis revealed some significant differences between the groups. Results suggest that cyclosporine impairs the antioxidant defense system and thus, leads to oxidant stress and peroxidation in rabbit hepatic tissues. It has been established that this process can be prevented by antioxidant vitamin supplementation.     

Is the Cell Death in Mesial Temporal Sclerosis Apoptotic?

PURPOSE: Mesial temporal sclerosis (MTS) is characterized by neuronal loss in the hippocampus. Studies on experimental models and patients with intractable epilepsy suggest that apoptosis may be involved in neuronal death induced by recurrent seizures. METHODS: We searched evidence for apoptotic cell death in temporal lobes resected from drug-resistant epilepsy patients with MTS by using the terminal deoxynucleotidyl transferase (TdT) and digoxigenin-11-dUTP (TUNEL) method and immunohistochemistry for Bcl-2, Bax, and caspase-cleaved actin fragment, fractin. The temporal lobe specimens were obtained from 15 patients (six women and nine men; mean age, 29 +/- 8 years). RESULTS: Unlike that in normal adult brain, we observed Bcl-2 immunoreactivity in some of the remaining neurons dispersed throughout the hippocampus proper as well as in most of the reactive astroglia. Bax immunopositivity was increased in almost all neurons. Fractin immunostaining, an indicator of caspase activity, was detected in approximately 10% of these neurons. Despite increased Bax expression and activation of caspases, we could not find evidence for DNA fragmentation by TUNEL staining. We also could not detect typical apoptotic changes in nuclear morphology by Hoechst-33258 or hematoxylin counterstaining. CONCLUSIONS: These data suggest that either apoptosis is not involved in cell loss in MTS, or a very slow rate of cell demise may have precluded detecting TUNEL-positive neurons dying through apoptosis. Increased Bax expression and activation of caspases support the latter possibility.     

Leukoaraiosis in stroke patients

Pathogenesis of leukoaraiosis (LA) is not clearly understood and its significance in patients with stroke remains undetermined. In the Neurology Department of Ankara Hospital, computed tomography (CT) examination of brain was performed for various reasons in 288 patients. LA was detected in 178 patients by the use of brain CT. Patients with LA had a higher incidence of hypertension history (70.8%) when compared with the non-LA group (57.3%; p <.05). There was no statistically significant difference in terms of sex, mean age, smoking, diabetes mellitus, history of cerebrovascular disease, cardiac failure, ischemic cardiac disease between patients with and without LA. We showed that LA is related to hypertension but not related to age, diabetes mellitus, or cardiac disease in our patient population.     

Spontaneous bacterial peritonitis caused by Brucella melitensis

This report presents a case of blood and ascitic fluid culture-proven spontaneous bacterial peritonitis caused by Brucella melitensis in a 67-y-old male with congestive heart failure. Ten cases of reported previously brucella peritonitis are reviewed, 3 of which were ascitic fluid culture negative.     

Alleles at the Nicastrin locus modify presenilin 1- deficiency phenotype

Presenilin 1 (PS1), presenilin 2, and nicastrin form high molecular weight complexes that are necessary for the endoproteolysis of several type 1 transmembrane proteins, including amyloid precursor protein (APP) and the Notch receptor, by apparently similar mechanisms. The cleavage of the Notch receptor at the "S3-site" releases a C-terminal cytoplasmic fragment (Notch intracellular domain) that acts as the intracellular transduction molecule for Notch activation. Missense mutations in the presenilins cause familial Alzheimer's disease by augmenting the "gamma-secretase" cleavage of APP and overproducing one of the proteolytic derivatives, the Abeta peptide. Null mutations in PS1 inhibit both gamma-secretase cleavage of APP and S3-site cleavage of the Notch receptor. Mice lacking PS1 function have defective Notch signaling and die perinatally with severe skeletal and brain deformities. We report here that a genetic modifier on mouse distal chromosome 1, coinciding with the locus containing Nicastrin, influences presenilin-mediated Notch S3-site cleavage and the resultant Notch phenotype without affecting presenilin-mediated APP gamma-site cleavage. Two missense substitutions of residues conserved among vertebrates have been identified in nicastrin. These results indicate that Notch S3-site cleavage and APP gamma-site cleavage are distinct presenilin-dependent processes and support a functional interaction between nicastrin and presenilins in vertebrates. The dissociation of Notch S3-site and APP gamma-site cleavage activities will facilitate development of gamma-secretase inhibitors for treatment of Alzheimer's disease.     

Are C‐reactive protein and homocysteine cardiovascular risk factors in obese children and adolescents?

Background: Several prospective epidemiological studies have demonstrated that high-sensitivity C-reactive protein (hsCRP) and plasma homocysteine (hcy) are predictors of future coronary events among healthy men and women. The aim of the present study was therefore to investigate a possible relationship between hsCRP, hcy levels and body mass index (BMI), relative weight (RW), serum leptin levels, and cardiovascular risk factors in obese children and adolescents.
Methods: The study involved 28 obese children and adolescents (13 girls, 15 boys; BMI>95‰ for age and sex), 4.5–15 years of age (mean 10.7 ± 0.6 years), who attended hospital for a basic obesity check-up. The association between hsCRP, hcy levels and BMI, RW, serum leptin levels, and cardiovascular risk factors such as blood pressure (BP), lipid profile, serum fasting insulin levels, and insulin resistance indexes, was investigated.
Results: Serum hsCRP level was positively correlated with BMI ( r = 0.512, P  < 0.01), RW ( r = 0.438, P  < 0.05), systolic and diastolic BP ( r = 0.498, P  < 0.01), serum leptin levels ( r = 0.457, P  < 0.05), but not with serum lipid, glucose, fasting insulin, plasma hcy levels or insulin resistance indexes. For hcy level, in contrast, no correlation was found with BMI, RW, systolic and diastolic BP, serum lipid levels, leptin, hsCRP, glucose, fasting insulin levels, or insulin resistance indexes.
Conclusions: hsCRP is correlated with BMI, RW, BP and leptin, which are risk factors for coronary heart disease, which supports the relationship between obesity, inflammation and atherosclerosis. hsCRP in childhood obesity might be a useful index to predict possible atherosclerotic events.