[Analysis on treatment of eight extremely severe burn patients in August 2nd Kunshan factory aluminum dust explosion accident].

Objective: To summarize the measures and experience of treatment in mass extremely severe burn patients. Methods: The clinical data and treatment of 8 extremely severe burn patients in August 2 Kunshan factory aluminum dust explosion accident who were admitted in the 100th Hospital of PLA on August 2nd, 2014, were retrospectively analyzed. There were 4 males and 4 females, aging 22-45 (34±7) years, with total burn area of 55%-98% [(89±15)%] total body surface area (TBSA) and full-thickness burn area of 45%-97% [(80±21)%] TBSA. All the 8 patients were accompanied with severe shock, inhalation injury, and blast injury. According to the requirements of former PLA General Logistics Department and Nanjing Military Command, a treatment team was set up including a special medical unit and a special care unit, with Chai Jiake from the First Affiliated Hospital of PLA General Hospital as the team leader, Zheng Qingyi from the 175th Hospital of PLA (the Affiliated Dongnan Hospital of Xiamen University) as the deputy leader, the 100th Hospital of PLA as the treatment base, and burn care, respiratory, nephrology, nursing specialists from the First Affiliated Hospital of PLA General Hospital, and the burn care experts and nursing staff from the 180th Hospital of PLA, 118th Hospital of PLA, 98th Hospital of PLA, and 175th Hospital of PLA, and nurses from the 85th Hospital of PLA, 455th Hospital of PLA, 101th Hospital of PLA, 113th Hospital of PLA as team members. Treatment strategies were adopted as unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns. With exception of one patient who received deep vein catheterization before admission, the other 7 patients were treated with deep vein catheterization 0.5 to 3.0 hours after admission to correct hypovolemic shock as soon as possible. Eight patients received tracheotomy, and 7 patients were treated with mechanical ventilation by ventilator in protective ventilation strategy with low tide volume and low volume pressure to assist breathing. Fiberoptic bronchoscopy was done one to three times for all the 8 patients to confirm airway injuries and healing status. Escharectomy and Meek dermatoplasty in the extremities of all the 8 patients were performed 3 to 6 days after injury for the first time. Escharectomy, microskin grafting, and covering of large pieces of allogeneic skin on the trunks of 4 patients were performed 11 to 16 days after injury for the second time. The broad-spectrum antibiotics were uniformly used at first time of anti-infective therapy, and then the antibiotics species were adjusted in time. The balance of internal environment was maintained and the visceral functions were protected. One special care unit was on responsibility of only one patient. Psychological intervention was performed on admission. The rehabilitative treatment was started at early stage and in company with the whole treatment. Results: Acute renal injury occurred in 5 patients within 36 hours after injury and their renal function was restored to normal 4 days after injury due to active adjustment of fluid resuscitation program. No pulmonary complications, such as severe pulmonary infection and ventilator-associated pneumonia, occurred in the survived patients. One of the 8 patients died, and the other 7 patients were cured successfully. The wounds were basically healed in 2 patients in 26 or 27 days by 2 or 3 times of operation, and in 5 patients by 4 or 5 times of operation. The basic wound healing time was 26-64 (48±15) days for all the 7 patients. Conclusions: Treatment strategies of unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns are the bases to successful treatment. Correcting shock as soon as possible is the prerequisite and closing wound as soon as possible is the key to successful treatment. Comprehensive treatment measures, such as maintaining and regulating the function of viscera, improving the body immunity, and preventing and treating the complications, are the important components to successful treatment. It is emphasized that in the treatment of mass extremely severe burn patients, specialist burn treatment should always be in the dominant position, and other related disciplines may play a part in auxiliary function.

Esculentoside A inhibits tumor necrosis factor, interleukin-1, and interleukin-6 production induced by lipopolysaccharide in mice.

Esculentoside A, a kind of saponin isolated from the root of the Chinese herb Phytolaca esculenta, is reported to possess potent anti-inflammatory effects in acute and chronic experimental models. In the present study, we investigated the effects of esculentoside A on the production of tumor necrosis factor (TNF), interleukin-1 (IL-1) and interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) in mice. In vitro experiments demonstrated that esculentoside A (0.1-10 mumol/l) significantly reduced the release of TNF from the peritoneal macrophages derived from mice pretreated with thioglycolate. IL-1 and IL-6 secretion was also obviously inhibited in a concentration-dependent manner by esculentoside A from 0.01 to 10 mumol/l. In vivo experiments demonstrated that detectable TNF was observed 0.25 h after injection, was maximal at 0.5 h, and returned to baseline at 4 h. Maximal production of IL-1 and IL-6 were observed to be 1 and 2 h, respectively, after injection of LPS. Pretreatment of mice with 5, 10, or 20 mg/kg esculentoside A once a day for 7 consecutive days dose-dependently decreased the TNF, IL-1 and IL-6 levels in the sera of mice following LPS challenge. TNF, IL-1, and IL-6 are important cytokines involved in the pathogenesis of inflammatory lesions. Inhibition of inflammatory cytokine production may contribute to the anti-inflammatory effects of esculentoside A.

Trioxane dimers have potent antimalarial, antiproliferative and antitumor activities in vitro.

A series of tetracyclic and tricyclic trioxane dimers has been prepared with ether and ester tethers of varying length and flexibility. Several of these trioxane dimers have been found to have potent and potentially therapeutically valuable antimalarial, antiproliferative, and antitumor activities in vitro.

Effects of Phytolacca acinosa polysaccharides I with different schedules on its antitumor efficiency in tumor bearing mice and production of IL-1, IL-2, IL-6, TNF, CSF activity in normal mice.

Effects of Phytolacca acinosa polysaccharides I (PAP-I), 5 approximately 40 mg/kg in timing of 7 times/wk, 3 times/wk and 1 time/wk on their antitumor efficiency in Sarcoma-180 bearing mice were comparatively investigated. The results confirmed that PAP-I (10 mg/kg, 3 times/wk) reached its optimal antitumor efficiency. Concanavalin A-, lipopolysaccharides-induced lymphocyte proliferation and the IL-2 production were tested in normal mice which were treated with PAP-I, 5 approximately 50 mg/kg in timing of 1 time/wk and 3 times/wk. The results showed that PAP-I could augment lymphocyte proliferation and IL-2 production in the group treated with PAP-I in timing of once a week. However, in the group 3 times/wk, PAP-I could significantly weaken lymphocyte proliferation and IL-2 production. Further studies on IL-1, TNF and IL-6 secreted from macrophages and the level of CSF activity in serum of normal mice with different schedules showed that PAP-I (10 mg/kg, 3 time/wk) was the best one in regulating the production of IL-1, TNF, IL-6 and CSF activity. M-CSF was confirmed in the serum by using monoclonal antibody of IL-3, GM-CSF and polyclonal antibody of M-CSF. These results suggested that the antitumor effect of PAP-I, may be mainly related to its augmenting effect on macrophages in mice.

Inhibitory effect of esculentoside A on tumour necrosis factor alpha production by human monocytes.

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. Previous experiments have shown that it has strong anti-inflammatory effects. Tumour necrosis factor (TNF) is a very important inflammatory mediator. It is known that there are two types of TNF-TNFalpha is from macrophages/monocytes and TNFbeta is from activated lymphocytes. In order to study the mechanism of the anti-inflammatory effect of EsA, it was determined whether TNFalpha production from human peripheral monocytes was altered by EsA under lipopolysaccharide (LPS)-stimulated conditions. EsA was found to decrease TNFalpha production in a dose-dependent manner at concentrations higher than 1 mumol/l EsA. Recent studies have shown that EsA has a curative effect on chocolate cyst and other inflammatory diseases. Our previous studies have shown that EsA could reduce the release of platelet activating factor (PAF) from rat macrophages, and inhibit interleukin-1 and interleukin-6 production from routine macrophages. The reducing effects of EsA on the release of TNFalpha, IL-1, IL-6 and PAF may explain its anti-inflammatory effect.

Brevitaxin, a new diterpenolignan from the bark of Taxus brevifolia.

The first terpenolignan, brevitaxin [1], has been isolated from the bark of Taxus brevifolia. Identification was carried out using spectral methods, and the regiochemistry and cytotoxicity of 1 are discussed.

Effects of triazolodiazepine on the production of interleukin-6 from murine spleen cells and rabbit synovial cells in vitro.

Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, acute phase anaphylactic reaction, and haematopoiesis. Lipopolysaccharide (6-24 mug/ml) significantly induced IL-6 release from murine spleen cells. In cultured rabbit synovial cells interleukin-1 (IL-1, 1-10 U/ml) induced IL-6 production in a concentration-dependent manner. Triazolodiazepine (Tri) is a hetrazepine platelet-activating factor antagonist. In this study we found that Tri (0.1-10 mumol/l) exerted strong inhibitory effects on LPS stimulated IL-6 production in murine spleen cells. Kinetic studies showed that the inhibition of IL-6 release was time-independent. In rabbit synovial cells Tri also reduced IL-6 release induced by IL-1 and tumour necrosis factor. Inhibition of cytokine production by Tri may partially explain its wide and strong anti-inflammatory effects.

Effects of Phytolacca acinosa polysaccharides I combined with interleukin-2 on the cytotoxicity of murine splenocytes against tumor cells.

Phytolacca acinosa polysaccharides I (PAP-I), a kind of purified polysaccharides, isolated from Phytolacca acinosa Roxb was found to significantly augment the cytotoxicity of murine splenocytes and interleukin-2 (IL-2) activated splenocytes against P815 tumor cells in vitro. The optimal concentration of PAP-I was 1 microgram.ml-1 and the peak level of the cytotoxicity against P815 tumor cells was reached on d 3-5. The supernatants collected from splenocytes cultured with PAP-I alone or in combination with IL-2 showed no effect on the cytotoxicity against P815 tumor cells. Splenocytes from mice injected ip with PAP-I, 5, 10 and 50 mg.kg-1, thrice a week produced more cytotoxicity against P815 and L929 tumor cells compared with the control group. PAP-I ip was shown to significantly increase IL-2 activated killer cell activity (LAK) against P815 tumor cells. The higher the dosage of PAP-I, the more potent the LAK activity was observed. These results confirmed that PAP-I can augment the cytotoxicity of murine splenocyte against tumor cells and LAK activity and warranted further evaluation of its clinical usefulness.

Leflunomide inhibits cytokine-induced DNA synthesis of rabbit synovial cells in culture.

The effects of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on DNA synthesis of rabbit synovial cells were studied. IL-1 beta 1000-10,000 U.ml-1, IL-6 10-1000 U.ml-1, TNF alpha 0.5-50 U.ml-1 and GM-CSF 1-100 ng.ml-1 concentration-dependently stimulated DNA synthesis in rabbit synovial cells in culture. Leflunomide (LFM) and its metabolite A77 1726 elicited an inhibitory effect on such cytokine-induced DNA synthesis of synovial cells. These results suggested that IL-1 beta, IL-6, TNF alpha and GM-CSF play a key role in the pathogenesis of rheumatoid arthritis. Inhibition of cytokine-induced proliferation of synovial cells by LFM may partially explain its antirheumatic activity.

Stent of shape-memory alloy for urethral obstruction caused by benign prostatic hyperplasia.

Dilation and positioning a stent in the prostatic urethra have become important alternatives for the management of benign prostatic hyperplasia (BPH), but both have significant drawbacks, namely the need to repeat the treatment in the former case and the conflict between the introducing means and the generation of sufficient expansile force in the latter case. A spiral of a Chinese titanium-nickel alloy with shape memory was implanted in 25 patients with BPH using a self-made coaxial sheath. With a follow-up of 3 to 20 months, the success rate is 92%. There has been no encrustation or migration of the spirals. We deem the spiral of this shape-memory alloy to be a good alternative in patients with BPH who are unfit for surgery.

Changes and Relationship of PAF and TNF in Rats with Myocardial Ischaemia and Reperfusion Injury.

IN THIS STUDY IT IS REPORTED THAT: (1) the levels of blood platelet-activating factor and serum tumour necrosis factor significantly increased after coronary ligation and reperfusion, compared with sham-ligated controls, in an anaesthetized rat model; (2) compared with vehicle controls, pretreatment with the PAF antagonist BN 50739 (10 mg/kg, i.v.) produced significant decreases in infarct size (from 29.6 +/- 4.0% to 22.4 +/- 2.1%, p < 0.05 after 3 h ligation, and from 28.5 +/- 9.5% to 10.5 +/- 4.5%, p < 0.01 after 4 h reperfusion) and the level of serum TNF (from 10.4 +/- 7.7 U/ml to 3.9 +/- 4.8 U/ml, p < 0.05); and (3) a significan positive correlation was found between the level of blood PAF or serum TNF and infarct size. The present results indicate that PAF and TNF may be important mediators involved in myocardial ischaemia and reperfusion injury, and that PAF antagonists may exert a protective effect on ischaemic or reperfused myocardium by inhibiting the interaction of PAF and TNF.

[Effect of Phytolacca acinosa polysaccharides I on production of colony-stimulating factors of mouse splenocytes in vitro].

Phytolacca acinose polysaccharides I (PAP-I), M(r) = 10,000, activated mouse splenocytes to produce colony-stimulating factors (CSF) in vitro. The level of CSF was tested by [3H]TdR uptaken by bone marrow cells and rmGM-CSF was used as standard. PAP-I (10-500 micrograms.ml-1) increased CSF production of the splenocytes treated with or without concanavalin A. When the concentration of PAP-I was 100 micrograms.ml-1, the level of CSF was about equivalent to that of rmGM-CSF 11.8 +/- 1.8 ng.ml-1. After a 3-d incubation of PAP-I with the splenocytes, CSF was assayed. The longer the incubation, the higher were the CSF concentrations. The CSF type in supernants of splenocytes induced by PAP-I was determined by IL-3 McAb, GM-CSF McAb, and M-CSF PcAb. The type of CSF was found to be interleukin-3.

Effect of platelet activating factor antagonist WEB 2086 on the production of TNF from murine peritoneal macrophages.

In the present study the effect of platelet activating factor (PAF) antagonist WEB 2086 on the production of tumor necrosis factor (TNF) from primed murine peritoneal macrophages was investigated. At 10(-6) and 10(-5) mol/L, WEB 2086 was found to significantly inhibit LPS induced TNF production from macrophages by activated thioglycollate solution. WEB 2086 inhibition of TNF release began 4 h after LPS stimulation and lasted 22 h with a peek at 16 h. The results showed that PAF might play an important role in the production of TNF. Four methods were compared in the bioassay of TNF. The data demonstrated that L-929 cells treated with actinomycin D and sodium fluoride were the most sensitive for the assay of TNF. This method was employed in this study.

[Effects of Phytolacca acinosa polysaccharide on splenic lymphocyte proliferation and cytokine secretion from splenic lymphocyte and macrophage].

The effects of Phytolacca acinosa polysaccharides I (PAP-I), a polysaccharide extracted from Phytolacca acinosa Roxb: on splenic lymphocyte proliferation and cytokines production from splenic lymphocyte and macrophage were studied. Lipopolysaccharides (LPS) and PAP-I were found to significantly augment splenic lymphocyte proliferation of normal BALB/c, nude BALB/c and NC mice in vitro, but concanavalin A (Con A) was shown to stimulate only normal BALB/c and nude BALB/c splenic lymphocyte proliferation. Also, PAP-I significantly enhanced Con A or LPS-induced lymphocyte proliferation and mixed lymphocyte reaction. Significant enhancement of colony stimulating factor (CSF) production was observed from splenic lymphocyte of normal BALB/c and nude BALB/c mice but not from NC mice when treated with PAP-I for 5 d. PAP-I was shown to significantly enhance interleukin-2 (IL-2) production from normal mice splenocyte and Con A stimulated normal mice splenocyte in a concentration-dependent fashion. Supernatant of PAP-treated macrophage (M phi) were collected and CSF activity was tested. The results confirmed that PAP-I can significantly stimulate M phi to secret CSF activity on d 1. The supernatant also contained a cytokine which exhibited a synergistic action with recombinant murine granular-macrophage CSF (RMGM-CSF) to stimulate mice bone marrow cell proliferation. PAP-I, 5-50 mg.kg-1, ip can enhanced splenic lymphocyte proliferation and IL-2 production. These findings indicate that PAP-I can augment immunologic function in vitro and in vivo.

Quantitative explanation on structure-carcinogenic activity relationship of aromatic amines by di-region theory.

Di-region theory, the theory for the mechanism of carcinogenesis, has been extended successfully on the quantitative structure-carcinogenic activity relationship (QSCAR) of 63 aromatic amines. A quantitative equation for the QSCAR of aromatic amines has been established by the mechanism conception of the specialized di-functional alkylation between the nitrenium ion of the amino group and the epoxide of the aromatic ring. The agreement between calculation and experiment comes up to 98%. Thus, it can now express the puzzling variation of the carcinogenicity of aromatic amines, as a comprehensible structure-chemical reactivity relationship.

[Inhibitory effect of esculentoside A on platelet activating factor released from calcimycin induced rat peritoneal macrophages].

Platelet activating factor (PAF) is a kind of inflammatory mediator. We used the method of aggregation of washed rabbit platelet to study the effect of esculentoside A (EsA) on the release of PAF from calcimycin (A23187)stimulated rat peritoneal macrophages and found that the release of PAF was inhibited by EsA in a time and dose dependent manner. The IC50 of EsA for the inhibition of PAF release was 1.5 mumol/L. Under the same condition, the release of PAF was also inhibited by mepacrine at 100 mumol/L. The results indicate that EsA is a potent inhibitor of PAF synthesis in rat peritoneal macrophages.

[Effects of Phytolacca acinosa polysaccharides I on cytotoxicity of macrophages and its production of tumor necrosis factor and interleukin 1].

The in vivo effects of Phytolacca acinosa polysaccharides I (PEP-I) on immunologic cytotoxicity of mouse peritoneal macrophages and its production of tumor necrosis factor (TNF) and interleukin 1 (IL-1) were studied. PEP-I 80, 160 mg/kg was given ip twice every 4 d. Both doses were found to have significant enhancing activity on macrophages cytotoxicity against S180 sarcoma cells and malignant transformed fibroblast L929 cells. Peritoneal activated macrophages were incubated with LPS for 2 and 24 h to induce TNF and IL-1, respectively. The TNF and IL-1 activities were tested from cytotoxicity against L929 cells in an absorbance assay of enzymatic reaction and proliferation of thymocytes co-stimulated assay separately. The optimal time for TNF production was found on d 8. Significant increases in TNF and IL-1 were observed. In comparison of the effect of PEP-I on TNF with that of known priming agent BCG, there was no difference between these two, but PEP-I had a high effect on IL-1. These results suggest that cytotoxicity of macrophages primed by PEP-I is closely related to its TNF and IL-1 production.

[Immunosuppressive and antiinflammatory activities of tripterine].

Tripterine is one of the active components isolated from Tripterygium wilfordii Hook.f. In this study tripterine was shown to inhibit the antibody response of mouse splenocytes to SRBC both in vitro and in vivo either by primary or secondary stimulation. Tripterine was also found to significantly inhibit cotton pellet induced granuloma growth in rats and depress the delayed hypersensitive reaction of mouse skin to dinitrochlorobenzene (DNCB). Besides, it also increased the sleeping time of mouse induced by pentobarbital sodium. From the results stated above, it appears that tripterine might be useful in the treatment of inflammatory diseases or autoimmune diseases.

Purified podophyllotoxin (CPH-86) inhibits lymphocyte proliferation but augments macrophage proliferation.

Purified podophyllotoxin (CPH-86) is an inhibitor of microtubular aggregation used in the treatment of cancer, psoriasis and rheumatoid arthritis. To better understand its immunopharmacology we examined its effects on human lymphocytes and monocytes and guinea pig macrophages. CPH-86 inhibits mitogen-induced human lymphocyte proliferation and macrophage growth factor-stimulated macrophage proliferation with ID50s of approximately 10(-7) M. The effect of CPH-86 on lymphocytes in conjunction with mitogen is nonlethal, evident during the early but not the late phases of proliferation, and associated with early increases in cyclic AMP levels. In contrast to these obviously inhibitory effects, CPH-86 (10(-7) M) alone induces IL-1 by human monocytes and, with mitogen, it induces IL-2 production by human lymphocytes. It directly stimulates macrophage proliferation and potentiates the effects of low doses of macrophage growth factor to do so. The latter effects may be mediated by colony stimulating factor production. The effects of CPH-86 are not mediated by inhibition of prostaglandin synthesis. The stimulation of monokine and lymphokine production by CPH-86 may represent positive features of its action and may be immunotherapeutic.