Tumor necrosis factor-alpha is a potent endogenous mutagen that promotes cellular transformation

Tumor necrosis factor-alpha (TNF-alpha) is an important inflammation cytokine without known direct effect on DNA. In this study, we found that TNF-alpha can cause DNA damages through reactive oxygen species. The mutagenic effect of TNF-alpha is comparable with that of ionizing radiation. TNF-alpha treatment in cultured cells resulted in increased gene mutations, gene amplification, micronuclei formation, and chromosomal instability. Antioxidants significantly reduced TNF-alpha-induced genetic damage. TNF-alpha also induced oxidative stress and nucleotide damages in mouse tissues in vivo. Moreover, TNF-alpha treatment alone led to increased malignant transformation of mouse embryo fibroblasts, which could be partially suppressed by antioxidants. As TNF-alpha is involved in chronic inflammatory diseases, such as chronic hepatitis, ulcerative colitis, and chronic skin ulcers, and these diseases predispose the patients to cancer development, our results suggest a novel pathway through which TNF-alpha promotes cancer development through induction of gene mutations, in addition to the previously reported mechanisms, in which nuclear factor-kappaB activation was implicated.     

Use of a modifier reduces inconsistency in the American Society of Anesthesiologists Physical Status Classification in parturients

In this study, we sought to determine whether there is a significant discrepancy among a group of practitioners when rating pregnant patients using the ASA Physical Status Classification and whether this discrepancy could be resolved with the addition of a modifier for pregnancy. Our results indicate that significant discrepancy occurs and that it is reduced with the use of the modifier, especially when referring to the healthy parturient.     

Finding hepatic portal venous gas in an adult patient: its significance

Portal venous gas is a well-established radiological finding in neonates. With the advancement in diagnostic imaging, more cases are being reported in adults. We present a 55-year-old man with radiological findings of both portal venous gas and pneumatosis intestinalis secondary to ischaemic necrotising enterocolitis, with subsequent fatality. The significance of finding portal venous gas and its possible aetiology is discussed.     

The effect of desflurane on rocuronium onset, clinical duration and maintenance requirements

Volatile anesthetics potentiate the effects of non-depolarizing agents. This study investigated the interaction between the inhalational anesthetic desflurane and rocuronium. Forty ASA I and II patients randomly received desflurane/N2O/fentanyl, or propofol/ N2O/fentanyl anesthesia, and rocuronium 0.6 mg/kg. Neuromuscular block was assessed at the adductor pollicis muscle. Block onset and clinical duration times were measured; a rocuronium infusion was started when the first twitch on train-of-four returned to 10% of control (T10%). Maintenance infusion requirements and recovery profiles (spontaneous and after reversal) were recorded until recovery of twitch to 90% of control (T90%). Rocuronium onset was prolonged by 67% (p = 0.034), clinical duration by 30% (p = NS), and infusion requirements were lower in the desflurane group (4.5 vs. 7.1 mg/kg/min, p = 0.003). Recovery times were not statistically different. Desflurane significantly delays the onset of neuromuscular block, potentiates rocuronium during maintenance infusion, but does not affect clinical duration or recovery.     

Large-scale preparation of human anti-third-party veto cytotoxic T lymphocytes depleted of graft-versus-host reactivity: a new source for graft facilitating cells in bone marrow transplantation

Induction of donor type chimerism in mildly prepared hosts without graft-versus-host disease (GvHD) is a most desirable goal in bone morrow transplantation. We have recently demonstrated in a mouse model that donor veto cytotoxic T lymphocytes (CTLs) can facilitate the induction of donor type chimerism in sublethally irradiated recipients without causing GvHD if they are effectively depleted of alloreactivity against host cells by means of stimulation against a third party. We extend this approach to human cells, by preparing CTLs in two major steps: primary culture in the absence of interleukin 2, leading to death by neglect of antihost clones, and addition of interleukin 2 and subsequent dilution of antihost clones as a consequence of the expansion of the anti-third-party clones. CTLs prepared in this way specifically suppress host cytotoxic T cells directed against antigens of the donor, but not against fourth-party antigens, as demonstrated in a standard (51)Cr release assay. We conclude that human anti-third-party CTLs afford a new source of veto cells that are depleted of potential graft-versus-host-reactive clones. The cells generated by this approach could potentially be used to facilitate engraftment of allogeneic hematopoietic stem cells.     

Lignans and their degraded derivatives from Sarcostemma acidum

Four lignans, sacidumlignans A-D (1-4), and two degraded lignan derivatives, sacidumols A (5) and B (6), along with four known compounds, (+)-pinoresinol, 9alpha-hydroxypinoresinol, perforatic acid, and peucenine-7-O-methyl ether, were isolated from the ethanolic extract of the whole plant of Sarcostemma acidum. The structures and relative configuration of these new compounds were elucidated on the basis of spectroscopic and chemical data, especially 2D NMR techniques. Sacidumlignan D (4) was assigned as a rearranged tetrahydrofuran lignan with an unprecedented skeleton. Sacidumlignan A (1) showed moderate antimicrobial activities against two Gram-positive bacteria in vitro.     

Clinical and psychological assessment on xinwei decoction for treating functional dyspepsia accompanied with depression and anxiety

The purpose of this study is to explore the psychological efficacy of Xinwei Decoction, a traditional Chinese herbal medicine, to treat functional dyspepsia (FD) accompanied with depression and anxiety. Seventy-three subjects, divided into three groups, had been given herbal medicine (Xinwei Decoction), prokinetic agent (Domperidone) and placebo, respectively for 8 weeks. Before and after treatment, all subjects were examined with FD symptom scale, Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA). As a result, the total scores of the three groups in FD symptom scale, HAMD and HAMA after treatment decreased in different levels, with the decrease in the herbal group more significant than the other two groups (p < 0.01), indicating the efficacy of the herbal medicine. The total effective rates of the herbal, Domperidone and placebo groups were 90%, 67% and 31%, respectively, which indicated significant effect differences between Xinwei Decoction and Domperidone (p < 0.05) and between Xinwei Decoction and placebo (p < 0.01), showing that the efficacy of herbal therapy was superior to that of the other two therapies. Furthermore, there was no one in the Domperidone and placebo groups being cured of depression and anxiety, while the curing rate in the herbal group was about 70%, indicating the efficacy of herbal medicine in comparison to that of Domperidone and placebo for anti-depression and anti-anxiety. The result demonstrated that Xinwei Decoction could not only alleviate FD symptoms but also relieve depression and anxiety.     

Pharmocokinetics and pharmacodynamics of single-dose triazolam: electroencephalography compared with the Digit-Symbol Substitution Test

AIMS: To investigate whether the electroencephalogram (EEG) directly reflects the CNS effects of benzodiazepines by evaluating the relation of the EEG to plasma drug concentrations and to Digit-Symbol Substitution Test (DSST) scores after a single dose of triazolam, a representative benzodiazepine agonist. METHODS: Thirteen healthy male subjects were given 0.375 mg triazolam or placebo in a double-blind crossover study. Plasma samples were collected during 8 h after dosage. Pharmacodynamic effects were measured by DSST and EEG at corresponding times. RESULTS: Pharmacokinetic parameters for triazolam were consistent with established values. Compared with placebo, triazolam significantly impaired psychomotor performance on the DSST (P < 0.001) and increased beta amplitude on the EEG (P < 0.002). DSST and EEG changes both closely tracked changes in plasma concentrations over time. The changes for the two measures were highly correlated with each other (r =-0.94, P < 0.001) based on aggregate values at individual time points. However, the variations in area under the curve of pharmacodynamic effect vs. time (AUCeffect) measured by either method did not reflect the variations in plasma AUC across individuals. The individual variability in AUCeffect from the EEG was similar to that measured by the DSST. CONCLUSIONS: Both the EEG and the DSST reflect the central benzodiazepine agonist effects of triazolam. Intrinsic variability in both measures is similar.     

Intravitreal dexamethasone as adjuvant in the treatment of postoperative endophthalmitis: a prospective randomized trial

Purpose To study whether intravitreal dexamethasone as adjuvant to intravitreal antibiotics improves the outcome in patients with suspected postoperative bacterial endophthalmitis. Design Prospective randomized clinical trial. Setting Tertiary referral center. Patient population Twenty-nine consecutive patients with suspected postoperative bacterial endophthalmitis within 6 weeks of cataract surgery. Intervention Patients underwent a vitreous biopsy followed by intravitreal injection of antibiotics (0.2 mg vancomycin and 0.05 mg gentamicin) and 400 μg dexamethasone or placebo. After 3–4 days the intravitreal injection of antibiotics and dexamethasone or placebo was repeated Primary outcome measure Snellen visual acuity at 3 and 12 months after treatment. Results In 20/29 patients (69%) the vitreous cultures were positive. 13/29 patients received dexamethasone. Seven patients had a functionally lost eye (final vision of hand movements or less), in four due to retinal detachment. Visual acuity tended to be better in the dexamethasone treated patients than in those given placebo, at both 3 months (P=0.055) and 12 months (P=0.080). Conclusion This small prospective, placebo-controlled series showed a trend towards a better visual outcome in patients with suspected bacterial endophthalmitis when treatment with intravitreal antibiotics was combined with intravitreal dexamethasone. Our findings justify a larger multicenter randomized study.