N-acetylcysteine attenuates ventilator-induced lung injury in an isolated and perfused rat lung model

N-acetylcysteine (NAC) suppresses the generation of reactive oxygen species (ROS) that are implicated in ventilator-induced lung injury (VILI). We thus hypothesised that NAC attenuates VILI. VILI was induced by mechanical ventilation with a tidal volume (Vt) of 15mlkg(-1) in isolated and perfused rat lung. NAC was administered in the perfusate prior to the onset of mechanical ventilation. A group ventilated with low Vt of 5mlkg(-1) served as control. Haemodynamics, lung injury indices, inflammatory responses and activation of apoptotic pathways were determined upon completion of the mechanical ventilation. There was an increase in lung permeability and lung weight gain after mechanical ventilation with high Vt, compared to low Vt. The levels of inflammatory cytokines including interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and macrophage inflammatory protein-2 (MIP-2) increased in lung lavage fluids; the concentrations of H(2)O(2) were higher in lung lavage fluids, and the expression of myeloperoxidase (MPO), JNK, P38, pAKT and caspase-3 in lung tissue was greater in the high Vt than in the low Vt group. The concentrations of glutathione (GSH) in lung tissue were higher in low Vt than those in high Vt. The administration of NAC increased GSH, attenuated ROS, cytokines, MPO, JNK, pAKT and caspase-3 and lung permeability associated with decreased activation of nuclear factor-κB. VILI is associated with inflammatory responses including the generation of ROS, cytokines and the activation of mitogen-activated protein kinase cascade. The administration of NAC attenuates the inflammatory responses, apoptosis and VILI in the isolated, perfused rat lung model.     

Pelvic vascular bed isolation in the management of radioresistant pelvic cancer

The term “pelvic vascular bed isolation” is given to our newly described type of cancer chemotherapy. The tissues underlying the bilateral vaginal mucosa are clamped for 4–6 hr. The hypogastric, superior gluteal, inferior gluteal, internal pudendal, obturator and ovarian arteries and veins are all ligated. MMC solution ranging from 50 to 80 mg is given into the hypogastric arteries. Pelvic isolation seldom caused prohibitive complications because the lumbar artery served as a collateral shunt by making its own way into the median sacral artery. We reported here controlling recurrent cervical cancer for about one and a half year in one case, and panhysterectomized radioresistant pelvic cancer for at least 3 mo in two cases with this type of cancer chemotherapy. Clinical benefit to these patients was also great.     

Modified pelvic vascular bed isolation chemotherapy: Theoretical basis,surgical procedure,and two clinical case reports

Recently, the surgical procedure of pelvic vascular bed isolation chemotherapy (PVI) was modified to avoid gluteal muscle necrosis. The modified technic was used to treat two cases of advanced, unresectable, severely hemorrhagic, and obstinately radioresistant cervical cancer during 1977 in our department. Local evidence of macroscopic, cytological, and histological malignancy was completely eradicated with the modified technic using the respective dose of 60 and 66 mg of mitomycin C (MMC), and also no macroscopic evidence of malignancy was found in the specimens surgically excised 4 to 5 weeks after the chemotherapy. However, histological examination detected definite malignancy in one specimen, and suspicious malignancy in the other. They have been surviving without evidence of malignancy during the past 17 and 18 months, respectively. The result of our recent study to establish the theoretical basis for PVI and its modified technic is also presented.     

Carcinostatic effect of pelvic vascular bed isolation chemotherapy in the management of cervical cancer

A patient with advanced and probably radioresistant cervical cancer underwent pelvic vascular bed isolation, and 60 mg of mitomycin C was given in a one-shot manner into the internal iliac arteries. Visual, cytological, and histological evidence of local malignancy and cytoscopic evidence of bladder invasion were all gone 2 weeks after the isolation. Macroscopic evidence of malignancy of the uterus and vagina surgically removed 3 weeks after the isolation also disappeared. However, a remnant of microscopic malignancy was found in a small area of one fragment of the cervix radially divided into eight sections.     

Pregnancy resulting from transfer of repeat vitrified blastocysts produced by in-vitro matured oocytes in patient with polycystic ovary syndrome

This report describes a live birth produced from repeat vitrification and thawing of blastocysts derived from in-vitro matured (IVM) oocytes in a woman with polycystic ovarian syndrome. Immature oocyte retrieval was performed on day 12 of her induced menstrual cycle. The patient was administered 10,000 IU of human chorionic gonadotrophin s. c. 36 h before immature oocyte retrieval. A total of 47 immature oocytes were collected. Following IVM of these immature oocytes, 76.6% (36/47) become mature (at metaphase II stage). Thirty oocytes (30/36, 86.1%) were normally fertilized following insemination by intracytoplasmic sperm injection. The fertilized zygotes (two-pronuclear stage) were co-cultured with cumulus cells in YS medium supplemented with 10% human follicular fluid. On day 5 after insemination, three blastocysts were transferred. Unfortunately, fresh embryo transfer did not result in pregnancy. The remaining 10 embryos developed to the expanded blastocyst stage. These remaining blastocysts were vitrified with electron microscope grids following artificial shrinkage. Three months later, three blastocysts were thawed due to a clinical error. Consequently, the embryos were revitrified. After a week, the three blastocysts were warmed again. Two of them developed to hatched blastocysts. Following transfer, a full-term pregnancy resulted in the delivery of healthy twins.     

Dextromethorphan efficiently increases bactericidal activity, attenuates inflammatory responses, and prevents group a streptococcal sepsis

Group A streptococcus (GAS) is an important human pathogen that causes a wide spectrum of diseases, ranging from mild throat and skin infections to severe invasive diseases such as necrotizing fasciitis and streptococcal toxic shock syndrome. Dextromethorphan (DM), a dextrorotatory morphinan and a widely used antitussive drug, has recently been reported to possess anti-inflammatory properties. In this study, we investigated the potential protective effect of DM in GAS infection using an air pouch infection mouse model. Our results showed that DM treatment increased the survival rate of GAS-infected mice. Bacterial numbers in the air pouch were lower in mice treated with DM than in those infected with GAS alone. The bacterial elimination efficacy was associated with increased cell viability and bactericidal activity of air-pouch-infiltrating cells. Moreover, DM treatment prevented bacterial dissemination in the blood and reduced serum levels of the proinflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-1β and the chemokines monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 2 (MIP-2), and RANTES. In addition, GAS-induced mouse liver injury was reduced by DM treatment. Taken together, DM can increase bacterial killing and reduce inflammatory responses to prevent sepsis in GAS infection. The consideration of DM as an adjunct treatment in combination with antibiotics against bacterial infection warrants further study.