Simulating the radial dose distribution for charged particles in water medium by a semi-empirical model: An analytical approach.

A computational semi-empirical model based on electronic radiation damage to medium has been presented to simulate the radial dose distribution. An analytical approach was used to calculate the deposited energy in water per unit mass within a cylindrical shell of unit length around the ion path at a radial distance between r and r + dr, the so-called radial dose distribution, RDD. Detail steps were given and the final radial dose integration over the electron range between Rmin and Rmax was solved numerically using the Mid-Point Method. A validation for the present model was presented by integrating the RDD over all possible radial distances, r to yield the tabulated LET of the ion. The validation was presented for a range of proton ions of different energies. The RDD for heavy charged particles of proton, alpha, Carbon and Oxygen ions of different energies in liquid water were obtained. Good agreement between the present model and experimental, theoretical, and Monte Carlo (Geant4-DNA) data were obtained for all ions under investigations.

Identification of plumericin as a potent new inhibitor of the NF-κB pathway with anti-inflammatory activity in vitro and in vivo.

BACKGROUND AND PURPOSE: The transcription factor NF-κB orchestrates many pro-inflammatory signals and its inhibition is considered a promising strategy to combat inflammation. Here we report the characterization of the natural product plumericin as a highly potent inhibitor of the NF-κB pathway with a novel chemical scaffold, which was isolated via a bioactivity-guided approach, from extracts of Himatanthus sucuuba, an Amazonian plant traditionally used to treat inflammation-related disorders. EXPERIMENTAL APPROACH: A NF-κB luciferase reporter gene assay was used to identify NF-κB pathway inhibitors from H. sucuuba extracts. Monitoring of TNF-α-induced expression of the adhesion molecules VCAM-1, ICAM-1 and E-selectin by flow cytometry was used to confirm NF-κB inhibition in endothelial cells, and thioglycollate-induced peritonitis in mice to confirm effects in vivo. Western blotting and transfection experiments were used to investigate the mechanism of action of plumericin. KEY RESULTS: Plumericin inhibited NF-κB-mediated transactivation of a luciferase reporter gene (IC50 1 µM), abolished TNF-α-induced expression of the adhesion molecules VCAM-1, ICAM-1 and E-selectin in endothelial cells and suppressed thioglycollate-induced peritonitis in mice. Plumericin exerted its NF-κB pathway inhibitory effect by blocking IκB phosphorylation and degradation. Plumericin also inhibited NF-κB activation induced by transfection with the constitutively active catalytic subunit of the IκB kinase (IKK-ß), suggesting IKK involvement in the inhibitory action of this natural product. CONCLUSION AND IMPLICATIONS: Plumericin is a potent inhibitor of NF-κB pathways with a new chemical scaffold. It could be further explored as a novel anti-inflammatory lead compound.

Cold induces reactive oxygen species production and activation of the NF-kappa B response in endothelial cells and inflammation in vivo.

BACKGROUND: Organs intended for transplantation are generally stored in the cold for better preservation of their function. However, following transplantation and reperfusion, the microvasculature of transplanted organs often proves to be activated. Extensive leukocyte adhesion and microthrombus formation contribute to failure of the transplanted organ. OBJECTIVES: In this study we analyzed cold-induced changes to the activation status of cultured endothelial cells, possibly contributing to organ failure. METHODS: We exposed human umbilical vein endothelial cells (HUVECs) to temperatures below 37 °C (mostly to 8 °C) for 30 min and upon rewarming to 37 °C kept incubating them for up to 24 h. We also in vivo locally exposed mice to cold. RESULTS: The exposure to low temperatures induced, in HUVECs, expression of the prothrombotic factors plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) and of the inflammatory adhesion molecules, E-selectin, intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Furthermore, upon rewarming for 30 min, we detected activation of the inflammatory NF-κB pathway, as measured by transient NF-κB translocation to the nucleus and IκBα degradation. Using butylated hydroxytoluene (BHT), a scavenger of reactive oxygen species (ROS), we further demonstrated that cold-induced NF-κB activation depends on ROS production. Local exposure to cold also, in vivo, induced ROS production and ICAM-1 expression and resulted in leukocyte infiltration. CONCLUSIONS: Our results point to a causative link between ROS production and NF-κB activation, suppression of which had been shown to be beneficial during hypothermic storage and subsequent rewarming of organs for transplantation.

Cortical excitability and transcallosal inhibition in chronic tinnitus: transcranial magnetic study.

INTRODUCTION: It has been proposed that tinnitus may be caused by maladaptive plasticity of processing in the central auditory pathways, and that this may be due in part to a generalised deficit in NMDA-dependent glutamatergic synapses. STUDY AIM: To test this hypothesis, we used transcranial magnetic stimulation to assess the excitability of a number of well-defined synaptic connections in the motor cortex of patients with tinnitus. PATIENTS AND METHODS: Thirty-seven patients with chronic tinnitus and 12 normal age- and sex-matched volunteers were used as a control group. We measured resting and active motor thresholds (rMT/aMT) and the duration of the contralateral and ipsilateral cortical silent periods (CSP and ISP). Short interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were evaluated using a paired pulse stimulation paradigm in the left (dominant) hemisphere. RESULTS: There was no difference between patients and healthy subjects in rMT or aMT or the onset latency of the ISP. The CSP was shorter in patients (P=0.046) whereas the ISP was longer than in healthy subjects (P=0.048) but there was no difference between the hemispheres nor any relation to tinnitus side in patients with predominantly unilateral symptoms. There was no difference in the time course of SICI/ICF between patients and control groups and no significant correlation between tinnitus handicap inventory (THI) score and any of the measures of cortical excitability. CONCLUSIONS: There are small changes incortical excitability in patients with chronic tinnitus. However, given the number of factors we examined in each individual, such minor changes seem unlikely to be an important factor in development of clinical symptoms.

In vitro induction of endothelial cell fibrinolytic alterations by Nigella sativa.

The effect of Nigella sativa (NS) L. oil (blackseed oil) on the fibrinolytic system of the human umbilical vein (HUV) and human uterine arterial (HUA) endothelial cells (ECs) in culture was studied. Both of them showed a concentration-dependent increase in tissue-type plasminogen activator (t-PA). A maximum effect was achieved with 50 microg oil/ml conditioned medium (CM) (1.3+/-0.15ng/10(4) cells/24h vs. control 0.7+/-0.06ng/10(4) cells/24h, and 0.38+/-0.04ng/10(4) cells/24h vs. control 0.24+/-0.02ng/10(4) cells/24h, for HUVEC and HUA-EC, respectively). At 100 microg/ml, there was a significant change in the amount of t-PA antigen produced by either HUVEC or HUA-EC (1.0+/-0.1 ng/10(4) cells/24 h or 0.28+/-0.02 ng/10(4) cells/24 h) as compared to control CM from cells grown under control conditions, but still less than that recorded at 50 microg oil/ml. Plasminogen activator inhibitor-type 1 increased the CM significantly and concentration-dependently in both cells. For HUVEC, the maximum effect was achieved at a concentration of 100 microg/ml (257.7+/-8.0 ng/10(4) cells/24 h vs. control 72.7+/-3.8 ng/10(4) cells/24 h). HUA-EC showed the maximum effect at a concentration of 100 microg/ml (171.6+/-4.4 ng/10(4) cells/24 h vs, control 53.8+/-3.7 ng/10(4) cells/24 h). This study suggests a role for NS oil in modulating the balance of fibrinolysis/thrombus formation by modulating the fibrinolytic potential of endothelial cells.

In vitro decreases of the fibrinolytic potential of cultured human fibrosarcoma cell line, HT1080, by Nigella sativa oil.

It is generally accepted that the fibrinolytic potential of tumor cells is related to their malignant phenotype. In the present study, Nigella sativa oil (NSO) was studied to evaluate its effect on the fibrinolytic potential of the fibosarcoma cell line HT1080 to elucidate whether this oil might have an antitumor activity through its modulation of the fibrinolytic potential of such cells. NSO produced a concentration-dependent inhibition of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor type 1 (PAI-1). When subconfluent HT1080 cells were conditioned with oil, a concentration (0.0-200 microg oil/ml)-dependent decrease in t-PA, u-PA and PAI-1 antigen was observed. There was also a concentration-dependent decrease (from 0.0 to 112.5 microg oil/ml) in the confluent cultures. The results showed that blackseed oil decreases the fibrinolytic potential of the human fibrosarcoma cell line (HT1080) in vitro, implying that inhibition of local tumor invasion and metastasis may be one such mechanism.

Adventitial cystic disease of the popliteal artery: diagnosis and treatment. A case report.

Adventitial cystic disease of the popliteal artery (ACDPA) is an unusual cause of a unilateral progressive intermittent claudication in young or middle-aged men. In the case described here, ultrasound (US) examination provided the preoperative diagnosis. The lesion was dealt with by simple evacuation of the cyst and excision of the wall. This simple treatment is all that is required in the majority of cases and provides good long-term results.

Direct determination of track etch rate and response of CR-39 to normal incidence high-energy heavy ions.

Response of CR-39 to high-energy heavy ions was investigated by using optical microphotographs of track profiles for Ar (480 MeV/n) and Ni (300 MeV/n). The depth dependence of track etch rate (VT) was determined experimentally by track length measurement. The results indicate that VT for the low REL Ar tracks is depth independent but for the high REL Ni tracks VT is gradually decreasing with depth. The region beyond 30 m depth inside the detector shows a stable region regarding the detector response for both ions.

Assessment of corticodiaphragmatic pathway and pulmonary function in acute ischemic stroke patients.

The aims of this study were to investigate the effect of stroke on the corticodiaphragmatic pathway and to clarify the relationships between neurophysiological data and degree of motor disability, site of infarction in CT scan, diaphragmatic excursion, blood gases and pulmonary function in stroke patients. The corticodiaphragmatic pathway was assessed using magnetic stimulation of the scalp sites and cervical roots. The study included 34 sequentially selected patients out of 250 patients with acute ischemic stroke. Twenty-five (age and sex matched) volunteers served as controls. Sixteen patients had cortical infarction, thirteen had subcortical infarction and five had both cortical and subcortical infarction. The mean Scandinavian Stroke Scale was 32.2. Decreased diaphragmatic excursion was observed in 41% of the patients. Twenty-four patients (70.5%) had abnormal magnetic evoked potentials (MEPs) of the affected hemisphere. In five patients MEPs were unelicitable from the affected hemisphere. The remaining nineteen patients had abnormal values of both cortical latency and central conduction time (CCT). Cortical latency, CCT, amplitude of compound muscle action potentials (CMAPs) and excitability threshold of the affected hemisphere were significantly altered compared to both the unaffected hemisphere and the control group. The patients with hemiplegia had a greater degree of hypoxia, hypocapnia and decreased serum bicarbonate level compared to the control group. Additionally, hemiplegic patients had a different degree of respiratory dysfunction. A statistically significant association was found between neurophysiological data and disability score, diaphragmatic excursion, site of infarction in CT scan and degree of respiratory dysfunction. Central diaphragmatic impairment may occur in acute stroke and could contribute to the occurrence of hypoxia in those patients.

Assessment of corticodiaphragmatic pathway and pulmonary function in acute ischemic stroke patients.

This study investigates the effect of stroke on the corticodiaphragmatic pathway and attempts to clarify the relationship between neurophysiological data and degree of motor disability, site of infarction in computerized tomography (CT) scan, diaphragmatic excursion, blood gases and pulmonary function in stroke patients. Using magnetic stimulation of the scalp sites and cervical roots, an assessment of corticodiaphragmatic pathway was made. The study included 34 sequentially selected patients from a total of 250 patients with acute ischemic stroke. Twenty-five (age- and sex-matched) volunteers served as controls. Sixteen patients had cortical infarction, 13 had subcortical infarction and five had both cortical and subcortical infarction. The mean according to the Scandinavian Stroke Scale was 32.2. Decreased diaphragmatic excursion was observed in 41% of the patients. Twenty-four patients (70.5%) had abnormal magnetic evoked potentials (MEPs) in the affected hemisphere. In five patients MEPs could not be elicited from the affected hemisphere; the remaining 19 patients had abnormal values of both cortical latency and central conduction time (CCT). Cortical latency, CCT, amplitude of compound muscle action potentials (CMAPs) and excitability threshold of the affected hemisphere were significantly altered compared with both the unaffected hemisphere and the control group. Those patients with hemiplegia had a greater degree of hypoxia, hypocapnia and decreased serum bicarbonate level compared with the control group. Also, hemiplegic patients had different degree of respiratory dysfunction. A statistically significant association was found between neurophysiological data and disability score, diaphragmatic excursion, site of infarction in CT scan and degree of respiratory dysfunction. Central diaphragmatic impairment may occur in acute stroke and could contribute to the occurrence of hypoxia in those patients.

Evaluation of surgical procedures for bilharzial strictures of the ureter.

A series of 35 patients, with unilateral hydronephrosis complicating bilharzial stricture of either the upper or the middle third of the ureter, was divided into 2 groups. Group A, comprising 21 patients, was treated by resection anastomosis. Group B, comprising 14 patients, was treated by other reparative procedures without resection of the stricture. The results of the surgical correction, assessed clinically and radiologically, showed that significantly better results were achieved with resection anastomosis than with the other procedures.

Effect of liquid diet on nude mouse gastrointestinal tract.

The nude (athymic) mouse is currently used to study the effect of gastrin on cancer xenografts. We sought to develop a hypogastrinemia nude mouse model for use in evaluating the effect of hypogastrinemia on such xenografts. Thirty-six non-tumor-bearing nude mice were studied. Eighteen received a nutritionally complete liquid diet; eighteen received standard chow. Six mice from each group were weighed and killed (nonfasting) on days 2, 8, and 15. Mean serum gastrin levels (+/- SEM) for the control group were 118.7 +/- 7.5, 118.7 +/- 8.7, and 118.0 +/- 7.5 pg/ml on days 2, 8, and 15, respectively. Serum gastrin levels for the liquid diet group significantly decreased to 87.0 +/- 7.6, 88.0 +/- 9.7, and 66.7 +/- 9.6 pg/ml on the same days. Animals in both groups gained weight normally; there were no significant weight differences between the two groups at any point. No histological abnormalities were seen in stomach, small intestine, colon, cecum, liver, pancreas, spleen or kidney. However, the liquid diet group showed atrophic changes in colon: significant reductions in colon weight and RNA content on days 8 and 15, and significant reduction in colon protein content on day 8. This model of hypogastrinemia is reliable and inexpensive. The nonsurgical nature of the preparation allows excellent survival in this immunodeficient animal.

Effect of cyclosporine on carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine.

Cyclosporine administration has been associated with the development of lymphomas in human transplant patients as well as animals. Its effect on the genesis of common epithelial carcinomas is unknown. To investigate this N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered in drinking water to Wistar rats. Seventy-five young healthy male animals were divided into six groups and received cyclosporine alone, cyclosporine followed by MNNG, MNNG alone, cyclosporine during MNNG administration, MNNG followed by cyclosporine, and no treatment. Cyclosporine seemed to have minimal overall health effects and no cancers were encountered in the group receiving this agent alone. Animals in all carcinogen-treated groups developed gastric and upper intestinal carcinomas by Week 39. No statistically significant differences among carcinogen-treated groups were evident with respect to tumor incidence, histology, or distribution. There appeared to be trends (not statistically significant) toward a greater incidence of small bowel carcinomas in animals receiving cyclosporine plus MNNG as compared to those receiving MNNG alone; greater multiplicity of small intestinal carcinomas in animals receiving cyclosporine after MNNG as compared to all other groups; and greater incidence of small bowel tumors greater than 1 cm3 in animals receiving cyclosporine after MNNG as compared to all other groups. The median total tumor volume in the animals receiving cyclosporine following carcinogen was significantly greater than in any other group. This study does not support a policy of aggressive surveillance for gastrointestinal carcinoma in the human population receiving cyclosporine.