Evaluation of the relationship between C677T variants of methylenetetrahydrofolate reductase gene and hyperhomocysteinemia in children receiving antiepileptic drug therapy

Homocysteine (Hcy) is a sulfur-containing amino acid involved in methionine metabolism. Elevated plasma Hcy concentration is a possible risk factor for vascular disease. Folate and vitamin B-12 are vitamins that are necessary for remethylization of Hcy to methionine. The methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in remethylation of Hcy to methionine and supplies the required 5-methyltetrahydrofolate as the methyl donor for this reaction. It is well known that some antiepileptic drugs (AED) can lead to hyperhomocysteinemia by affecting the levels of folate and vitamin B-12. The C677T variant of MTHFR gene can also lead to hyperhomocysteinemia particularly when serum folate level is decreased. In this study, we investigated the levels of serum folate, vitamin B-12 and Hcy in epileptic patients receiving carbamazepine (CBZ) or valproic acid (VPA) as monotherapy, and we also evaluated the probable contribution of the C677T variant of MTHFR gene in hyperhomocysteinemia. A total of 93 patients with idiopathic epilepsy receiving CBZ or VPA as monotherapy were included in this study. CBZ and VPA groups consisted of 29 and 64 patients, respectively. The control group comprised 62 healthy children. We measured serum folate, vitamin B-12 and Hcy levels in each group. We found that mean serum folate level was statistically lower and mean Hcy level was higher in epileptic patients receiving CBZ or VPA when compared with those of controls'. We also determined the C677T variants of MTHFR gene (as normal, heterozygote or homozygote) in epileptic patients. We compared the variant groups for serum folate, vitamin B-12 and Hcy levels and found no significant differences among them. In conclusion, C677T variants of MTHFR gene have no contribution in hyperhomocysteinemia in epileptic patients receiving CBZ or VPA.     

A heterotopic ossification related to temporary placement of a skull bone flap. Case report

The authors report on a 19-year-old man who sustained a traumatic brain injury. Following decompressive craniotomy, he suffered from an unusual heterotopic ossification due to the temporary placement of the skull bone flap in his thigh. To the best of the authors' knowledge, this is the first time that a possible causal relationship between these entities has been reported in the literature.     

Early Decay of Pain-related Cerebral Activation in Functional Magnetic Resonance Imaging: Comparison with Visual and Motor Tasks

Background: Although pain-related activation was localized in multiple brain areas by functional imaging, the temporal profile of its signal has been poorly understood. The authors characterized the temporal evolution of such activation in comparison to that by conventional visual and motor tasks using functional magnetic resonance imaging.

Methods: Five right-handed volunteers underwent whole brain echo-planar imaging on a 3 T magnetic resonance imaging scanner while they received pain stimulus on the right and left forearm and performed visually guided saccade and finger tapping tasks. Pain stimulus on the right and left forearm consisted of four cycles of 15-s stimulus at 47.2-49.0[degrees]C, interleaved with 30-s control at 32[degrees]C, delivered by a Peltier-type thermode, and visually guided saccade and finger tapping of three cycles of 30-s active and 30-s rest conditions. Voxel-wise t statistical maps were standardized and averaged across subjects. Blood oxygenation level-dependent signal time courses were analyzed at local maxima of representative activation clusters (t > 3.5).

Results: Pain stimulus on the right forearm activated the secondary somatosensory (S2), superior temporal, anterior cingulate, insular, prefrontal cortices, premotor area, and lenticular nucleus. Pain stimulus on the left forearm activated similar but fewer areas at less signal intensity. The S2 activation was dominant on the contralateral hemisphere. Pain-related activation was statistically weaker and showed less consistent signal time courses than visually guided saccade- and finger tapping-related activation. Pain-related signals decayed earlier before the end of stimulus, in contrast to well-sustained signal plateaus induced by visually guided saccade and finger tapping.     

Ethanol Inhibits Spontaneous Activity of Central Nucleus of the Amygdala Neurons but Does Not Impair Retention in the Passive-Avoidance Task

BACKGROUND: Behavioral studies using pharmacological manipulations that increase neuronal activity of the central nucleus of the amygdala (CeA) have implicated the CeA in enhancement of memory modulation. To date, however, there has been a dearth of studies investigating the effect of a drug that decreases CeA activity on memory modulation-a drug that inhibits the neuronal activity of the CeA might be expected to impair memory modulation. To determine whether ethanol inhibits CeA activity and, if so, whether decreased CeA activity is associated with impairment of memory modulation, this study investigated the effect of ethanol on spontaneous single-unit activity of CeA neurons and retention in the passive-avoidance task. METHODS: The effect of ethanol (0.35, 0.75, 1.5, 2.5 g/kg) was determined on spontaneously firing neurons in the CeA in urethane-anesthetized rats by use of standard in vivo single-unit electrophysiological recording techniques. Additionally, the effect of ethanol when administered immediately after training in a standard passive-avoidance task was determined on retention the following day. RESULTS: Ethanol profoundly inhibited spontaneous CeA firing rates in urethane-anesthetized rats at all doses tested. Maximal inhibition was related to dose. Each dose of ethanol significantly inhibited CeA activity within 15 min of administration; within 35 min of administration, 0.75 g/kg of ethanol inhibited CeA activity by 65.2%, and the highest dose (2.5 g/kg) produced nearly complete suppression of CeA activity (81.3%). Although ethanol markedly inhibited CeA activity, these same doses of ethanol failed to impair retention in the passive-avoidance task: 0.35, 0.75, 1.5, and 2.5 g/kg of ethanol, administered immediately after training, failed to alter latency to step-through the following day. CONCLUSIONS: These results show that ethanol profoundly inhibits spontaneous CeA activity and suggest that inhibition of the CeA is not sufficient to impair retention in the passive-avoidance task.     

Large outbreaks of Salmonella Typhimurium phage type 135 infections associated with the consumption of products containing raw egg in Tasmania

This report describes one of the largest egg-associated outbreaks of foodborne illness in Australia for many years. Between June and December 2005, five outbreaks of Salmonella Typhimurium phage type 135 were identified in Tasmania, leading to 125 laboratory-confirmed cases. Public health investigations included case and food handler interviews, cohort studies, environmental health investigations of food businesses, microbiological testing, traceback, and inspections and drag swabbing of an egg farm. These investigations enabled identification of foods containing raw egg or foods contaminated through inadequate food handling and/or storage procedures as possible vehicles for infection. A particular poultry farm was reported as the common source of eggs. Interventions targeting the general public and food handlers to promote better handling of egg products, and advice to egg producers regarding harm minimisation strategies led to the series of outbreaks being brought under control.     

Inhibition of antibacterial activity of himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus, by fatty acid sodium salts.

Himastatin, a cyclohexadepsipeptide antibiotic, had in vivo antitumor activity against localized P388 leukemia and B16 melanoma but had no distal site antitumor activity. An in vitro Bacillus subtilis well-agar diffusion assay was employed to test the hypothesis that himastatin was enzymatically inactivated. The activity of himastatin against B. subtilis was inhibited when himastatin was mixed with mouse liver S9 fraction and microsomes. However, subsequent investigations demonstrated that the markedly decreased antibacterial activity was not enzymatic in nature but was related to the presence of certain fatty acid salts. Saturated fatty acid sodium salts with a carbon chain number of 8 or more reduced the antimicrobial activity of himastatin 50 to 100 times. If antibiotics such as ampicillin, bacitracin, chloramphenicol, and tunicamycin were used in place of himastatin, no meaningful reduction in antibacterial activity occurred. However, the antibacterial activity of the membrane-active peptide antibiotic polymyxin B, but not that of polymyxin E (colistin), was reduced in a manner similar to that of himastatin. Importantly, the activity of himastatin against HCT-116 colon adenocarcinoma cells in soft agar was markedly reduced in the presence of sodium palmitate as the reference fatty acid salt. The data indicate that himastatin may be trapped in micelles in vitro. It may be speculated that the lack of distal site antitumor activity resulted from similar complex formation between himastatin and lipids in vivo. The results also suggest that the cancer cytotoxic and antimicrobial effects of himastatin may result from interactions with the cell membrane.     

Hemostasis and cancer: tumor cells induce the expression of tissue factor-like procoagulant activity on endothelial cells

BACKGROUND AND OBJECTIVES: Clotting activation and thromboembolic manifestations are common features in patients with cancer. The two-way interaction between tumor cells and host cells is of crucial importance in this context. In the present study we investigated the effect of tumor cell-endothelial cell co-culture on the expression of procoagulant activity in the mixed cell populations. DESIGN AND METHODS: Human tumor cell lines (HL60 promyelocytic leukemia and HeLa uterine cervical cancer) and human umbilical vein endothelial cells (HUVEC) were cultured in vitro according to standard procedures. Procoagulant activity was studied in a coagulometer and was found to be tissue factor-like. A calibration curve was obtained with decreasing concentrations of rabbit brain thromboplastin (RBT) and the procoagulant activity of both tumor cells and HUVEC was expressed as RBT U/10(5) cells. RESULTS: Before incubation procoagulant activity (means S.E.) was found to be 0.18 +/- 0.04 U in HUVEC, 9.8 +/- 1.9 U in HL60 cells, 11.9 +/- 2.2 U in HeLa cells, 7.2 +/- 1.4 U in a mixed HL60 cell-HUVEC population (ratio 2:1) and 8.5 +/- 2.0 in a mixed HeLa cell-HUVEC population (ratio 2:1). Incubation at 37 degrees C for up to 4 hours of tumor cells or HUVEC alone did not produce any change in procoagulant activity. In contrast, co-incubation of tumor cells with HUVEC for 4 hours was followed by a significant increase in procoagulant activity of the mixed cell populations. Addition of supernatants from tumor cells, HUVEC or tumor cell-HUVEC co-cultures to HUVEC or tumor cells showed that the tissue factor-like procoagulant activity generated during coincubation was localized on HUVEC. INTERPRETATION AND CONCLUSIONS: Our results show that the close interaction of tumor cells with endothelial cells may induce surface expression of tissue factor in the latter. This effect could represent an additional mechanism of clotting activation in patients with cancer.     

Intestinal obstruction caused by a strangulated Morgagni hernia in an adult patient

A Morgagni hernia is a congenital herniation of abdominal contents into the thoracic cavity through a retrosternal diaphragmatic defect. The reported incidence of congenital diaphragmatic hernias is estimated to be 1 in between 2000 to 5000 births. Morgagni hernias comprise 2% of diaphragmatic hernias. Most Morgagni hernias are found and repaired in children, but 5% are found in adults. They are usually asymptomatic and often found incidentally on chest radiography. Symptoms of these hernias are attributable to the herniated viscera. Morgagni hernias containing bowel may require repair on presentation because of the risk of incarceration. We present a case of an incarcerated and strangulated Morgagni hernia in a 71-year-old woman admitted to our clinic for abdominal pain and symptoms of intestinal obstruction. The diagnosis was made preoperatively by chest radiography, sonography, and computed tomography. Emergent laparotomy was performed, with the herniated transverse colon and omentum reduced into the abdomen. The diaphragmatic defect was repaired, followed by resection of the strangulated omentum. In conclusion, a Morgagni hernia may cause intestinal obstruction. Routine radiographic studies are usually sufficient to arrive at the diagnosis, but a CT scan and sonography may be necessary. Laparotomy is appropriate for the management of symptomatic adult patients with Morgagni hernias, particularly those with findings of intestinal strangulation, with laparoscopic treatment an alternative approach in selected cases.