Compromised concentrations of ascorbate in fluid lining the respiratory tract in human subjects after exposure to ozone

OBJECTIVES: Ozone (O3) imposes an oxidative burden on the lung in two ways. Firstly, directly as a consequence of its oxidising character during exposure, and secondly, indirectly by engendering inflammation. In this study the second pathway was considered by ascertaining the impact of O3 on the redox state of the fluid lining the respiratory tract 6 hours after challenge. METHODS: Nine subjects were exposed in a double blind crossover control trial to air and 200 ppb O3 for 2 hours with an intermittent exercise and rest protocol. Blood samples were obtained and lung function (forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1)) assessed before, immediately after, and 6 hours after exposure. Bronchoalveolar lavage (BAL) was performed 6 hours after challenge. Inflammation was assessed in BAL fluid (total and differential cell counts, plus myeloperoxidase concentrations), and plasma and BAL fluid redox state were determined by measuring concentrations of antioxidants and markers of oxidative damage. RESULTS: Neutrophil numbers in BAL fluid increased 2.2-fold (p = 0.07) 6 hours after exposure and this was accompanied by increased myeloperoxidase concentrations in BAL fluid (p = 0.08). On the other hand, BAL fluid macrophage and lymphocyte numbers decreased 2.5-fold (p = 0.08) and 3.1-fold (p = 0.08), respectively at this time. Of the antioxidants examined, only ascorbate in BAL fluid was affected by O3, falling in all subjects relative to air values (0.1 (0.0-0.3) v 0.3 (0.2-1.2) mumol/l (p = 0.008)). A marginal decrease in plasma ascorbate was also detected at this time (p < 0.05). Although the decrease in macrophage numbers seemed to be causally related to the increase in neutrophils (R = -0.79), myeloperoxidase concentrations (R = -0.93) and ascorbate concentrations (R = 0.6), no clear associations were apparent between ascorbate changes and neutrophils or myeloperoxidase concentration after O3. CONCLUSIONS: Ascorbate in the fluid lining the respiratory tract is depleted as a consequence of O3 exposure at 6 hours after exposure. This was contemporaneous with, although not quantitatively related to the increase in neutrophil numbers and myeloperoxidase concentrations. Decreased macrophage numbers 6 hours after O3 related to the degree of neutrophilic inflammation with populations conserved where ascorbate concentration in the fluid lining the respiratory tract were high after exposure. These results imply that ascorbate has a critical protective role against inflammatory oxidative stress induced by O3.

 

     

Phase II trial of circadian infusion floxuridine (FUDR) in hormone refractory metastatic prostate cancer

Circadian administration of chemotherapy has been reported to decrease toxicity and possibly enhance efficacy. Between March 1991 and December 1993, 18 evaluable patients with progressive, hormone-refractory metastatic prostate cancer were treated in this phase II trial of circadian infusion floxuridine (FUDR). The drug was delivered through a central venous catheter using a CADD-Plus computerized pump such that approximately 70% of the drug was administered between 3 and 9 p.m. and the rest (30%) was administered between 9 p.m. and 3 p.m. The dose of FUDR was 0.15 mg/kg/day × 14 days every 4 weeks. A total of 79 complete cycles was administered.Two of 18 evaluable patients (11.1%) had decreases in PSA lasting five and eight months. No objective responses or improvement in bone scans was noted. The major toxicity observed was diarrhea. Although circadian infusion FUDR is feasible and tolerable, it has limited activity in hormone refractory prostate cancer.     

Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species.

Nitric oxide, NO, which is generated by various components of the immune system, has been presumed to be cytotoxic. However, NO has been proposed to be protective against cellular damage resulting during ischemia reperfusion. Along with NO there is often concomitant formation of superoxide/hydrogen peroxide, and hence a synergistic relationship between the cytotoxic effects of nitric oxide and these active oxygen species is frequently assumed. To study more carefully the potential synergy between NO and active oxygen species in mammalian cell cytotoxicity, we utilized either hypoxanthine/xanthine cell cytotoxicity, we utilized either hypoxanthine/xanthine oxidase (a system that generates superoxide/hydrogen peroxide) or hydrogen peroxide itself. NO generation was accomplished by the use of a class of compounds known as "NONOates," which release NO at ambient temperatures without the requirement of enzyme activation or biotransformation. When Chinese hamster lung fibroblasts (V79 cells) were exposed to hypoxanthine/xanthine oxidase for various times or increasing amounts of hydrogen peroxide, there was a dose-dependent decrease in survival of V79 cells as measured by clonogenic assays. However, in the presence of NO released from (C2H5)2N[N(O)NO]-Na+ (DEA/NO), the cytotoxicity resulting from superoxide or hydrogen peroxide was markedly abrogated. Similarly, primary cultures of rat mesencephalic dopaminergic cells exposed either to hydrogen peroxide or to hypoxanthine/xanthine oxidase resulted in the degradation of the dopamine uptake and release mechanism. As was observed in the case of the V79 cells, the presence of NO essentially abrogated this peroxide-mediated cytotoxic effect on mesencephalic cells.     

An electromyographic method for the assessment of naloxone-induced abstinence in morphine-dependent rats

Summary The electromyographic (EMG) activities of suprahyoideal muscle were recorded to measure naloxone-precipitated abstinence signs in morphine-dependent rats anesthetized with urethane (1 g/kg). Rats were rendered dependent on morphine by implanting 2 morphine pellets (75 mg each) and abstinence signs were induced by intravenous injections of various doses of naloxone at different times after pellet implantation. Three precipitated abstinence signs, a) myoclonic twitch activity (MTA), b) mastication, and c) body shakes were observed on EMG recordings after the injection of naloxone. Of these symptoms, only the MTA induced by naloxone (10 g/kg) occurred 4 h after pellet implantation and its sensitivity to naloxone increased with prolonged pellet implantation. Both mastication and precipitated shakes could be induced at 24 h. However, higher doses of naloxone were required to produce the shakes than is required to induce mastication. There appears to be a positive correlation between the intensity of naloxone-induced MTA and the degree of physical dependence on morphine. Since the MTA and mastication can be induced by low doses of naloxone in morphine-dependent rats, we suggest that these two parameters may be used to detect morphine abstinence signs in this species.Deceased February 13, 1979     

Giant ameloblastoma of the upper jaw

Ameloblastoma is the most frequently seen epithelial Odontogenic tumour, relatively uncommon, comprising about 1% of tumours and cysts arising from the Jaws.     

Predicting low birth weight delivery using maternal nutritional and uterine parameters

At the Institute of Medical Sciences, Banaras Hindu University in Varanasi, India, health workers took anthropometric measurements and hemoglobin level of 196 pregnant women at gestation of 37-41 weeks and of their singleton newborns to detect a combination of maternal nutritional and uterine parameters which could be used to screen mothers at high risk of delivering a low birth weight (LBW) infant ( 2500 g). The maternal anthropometric measurements included pre- and post-delivery weight, height, head and midarm circumference, fundal height, and abdominal girth. Weight, height, head and midarm circumference, and hemoglobin were significantly correlated with birth weight. Pre-delivery weight was better correlated than post-delivery weight with birth weight (r value = 0.4966 vs. 0.3494). The correlation between pre-delivery weight and birth weight remained, even when hemoglobin and one of the uterine parameters were controlled simultaneously. Hemoglobin was an independent significant predictor of birth weight, when all other variables were controlled simultaneously. Both fundal height and abdominal girth were significantly associated with birth weight, when all other variables were controlled simultaneously. Fundal height had a greater difference in means of birth weight than did abdominal girth (960 vs. 871 g). If the fundal height was less than 25 cm, all infants had a LBW. If the fundal height was greater than 35 cm, only one infant had a LBW. The multiple regression equation using pre-delivery weight, hemoglobin, fundal height, and abdominal girth (all independent significant parameters) to estimate birth weight accounted for 70.5% variation. Researchers tested the equation on 118 consecutive full-term singleton newborns. The equation predicted LBW in 32 of the 36 actual LBW deliveries. The estimated birth weights in the 4 actual but missed cases were 2620, 2600, 2566, and 2826 g. This equation can be successfully used to screen pregnant women for LBW.     

Evaluation of facial fat distribution using magnetic resonance imaging

Magnetic resonance imaging (MRI) provides noninvasive images of facial and neck fat for a variety of conditions. It accurately maps the soft tissues pre- and postoperatively, enabling surgeons to precisely and objectively assess results of soft tissue facial contouring and fat transplantation. The risks of MRI are few. It has the potential to provide aesthetic surgeons with a more scientific means of comparing various techniques of fat contouring.     

Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation.

Permeability of tumor vasculature can be a major barrier to successful drug delivery, particularly for high molecular weight agents such as monoclonal antibodies and their diagnostic or therapeutic conjugates. In this study, changes in permeability of SCCVII tumor vessels after radiation treatment were evaluated by dynamic magnetic resonance imaging as a function of time after irradiation using a generation-8 polyamidoamine dendrimer (G8-Gd-D)-based magnetic resonance imaging contrast agent shown previously to be confined to tumor blood vessels. Tumor irradiation consisted of either single doses (2-15 Gy) or various daily fractionated doses (5 days). A single radiation dose of 15 Gy resulted in significant transient image enhancement of the tumor tissue with a maximum occurring between 7 and 24 hours after radiation treatment. No observable enhancement was recorded for fractionated radiation doses. Use of dynamic magnetic resonance imaging coupled with G8-Gd-D provides an exquisite methodology capable of defining the timing of enhanced permeability of macromolecules in tumors after irradiation. Such information might be applied to optimize the efficacy of subsequent or concurrent therapies including radiolabeled antibodies or other anticancer agents in combination with external beam therapies.     

Chrome induced nasal septal perforation-An occupational hazard

86 patients, working in a chemical factory dealing with Chrome manufacturing job, were referred by Health Inspectai to F S 1 S Hospital O PD 32 patients out of above were found to be having Nasal septal perforation and were recommended to Medical Board for consideration of compensation as cases of Occupational hazard     

Prophylactic Amnioinfusion During Labour Complicated by Meconium

EDITORIAL COMMENT: This study of amnioinfusion during labour complicated by the known passage of meconium shows that the technique seems clinically worthwhile, even in a centre without facilities for electronic fetal heart monitoring or scalp blood pH and blood gas analysis. The series is small and more data from larger studies is required to test the conclusions reported by the authors.
Summary: A prospective study to see the safety and efficacy of transcervical amnioinfusion in labour complicated by meconium-stained amniotic fluid (MSAF) was carried out in a teaching hospital with limited resources. Fifty patients in labour with meconium-stained amniotic fluid and fulfilling the inclusion criteria (vertex presentation, gestational age of 36 weeks or more, no medical or obstetrical complications and normal fetal heart rate at time of inclusion) were taken for the study; 25 patients received amnioinfusion. The control group received only supportive therapy. Labour outcome was compared in the 2 groups. The incidence of Caesarean section was seen to be decreased but neonatal parameters showed no significant difference in the amnioinfusion group.