ANALYSIS OF AIR POLLUTION PARTICULATE-MEDIATED OXIDANT STRESS IN ALVEOLAR MACROPHAGES

Adverse health effects of urban air pollution particulates may be attributable to particle mediated oxidant stress and inflammation. Intracellular oxidant production in normal hamster alveolar macrophages (AMs) was measured upon exposure to concentrated ambient particulates (CAPs), residual oil fly ash (ROFA), and their water-soluble and particulate fractions. ROFA and CAPs caused increases in dichlorofluorescin (DCFH) oxidation, a fluorescent measure of intracellular reactive oxygen species (ROS) production, comparable to the positive control, phorbol myristate acetate (PMA). The water-soluble component of both CAPs and ROFA (CAPs, S and ROFA, S) significantly increased AM oxidant production over negative control. CAPs samples and components showed substantial day-to-day variability in their oxidant effects. Metal chelation by desferrioxamine (DF, 1 mM) caused significant inhibition of particulate-induced AM oxidant production. ROFA exposure resulted in increased macrophage inflammatory protein-2 (MIP-2) message in AMs and in increased tumor necrosis factor alpha(TNF-alpha) production by the monocyte-macrophage cell line, RAW 264.7. TNF- production was inhibitable by the antioxidant N -acetylcysteine (NAC). The data suggest that metal components adsorbed to urban air pollution particulates can significantly contribute to particulate ability to cause oxidant stress and cytokine production in AMs.     

Methadone titration in opioid-resistant cancer pain

Aim: To assess the use of methadone in patients with cancer pain who fail to respond to increasing doses of other opioids or experience intolerable side-effects from them.
Method: Inpatients of a specialist palliative care unit were titrated onto oral methadone. The dose was calculated as 10% of the previous morphine equivalent dose, up to maximum of 40 mg, given every 3 h as required for analgesia. When daily requirements were stable it was divided into two regular doses. Pain was assessed on a five-point verbal rating score (VRS): a good response was defined as a fall in VRS of two points or more. Results are expressed as median (range).
Results: Thirty-three patients (13 men, 20 women, age 61 (34-91) years), 26 with inadequate analgesia and seven with intolerable opioid related side-effects, were converted to methadone from diamorphine (12), morphine (19) or fentanyl (two). Morphine equivalent dose was 480 (20-1200) mg/day prior to titration. Pain was neuropathic (11), nociceptive (three) or mixed (19). Stabilisation on methadone was complete in 3 (2-18) days in 29 (88%) patients at 80 (20-360) mg/day. Twenty-six (78%) had a good response. Four (12%) patients were withdrawn during titration (three entered terminal phase, one failed to respond). During follow-up 15 (45%) required alteration of methadone dose. Twenty-three (70%) patients were discharged home at 12 (4-26) days. In all cases the stable dose of methadone was less than the previous morphine equivalent, and there was a weak correlation between them.
Conclusions: This method of methadone titration often results in improved pain control in patients with morphine resistance or intolerance. It requires careful titration in a specialist inpatient unit as there is no reliable formula for dose equivalence.     

Outcome of extremely low birthweight infants at the University Hospital of the West Indies, Jamaica

OBJECTIVE: To describe the early outcome of extremely low birthweight infants delivered at the University Hospital of the West Indies. METHODS: A two-year retrospective review of the charts of all live, inborn extremely low birthweight infants admitted to the neonatal unit between January 1, 2002 and December 31, 2003 was conducted Differences between survivors and non-survivors were determined using analysis of variance and predictors of outcome were determined using multiple regression models. RESULTS: During the study period, 47 extremely low birthweight infants were admitted to the neonatal unit. The mean +/- SD birthweight and gestational age of these infants were 780 +/- 137 g and 27 +/- 2 weeks respectively. Twenty (43%) infants survived Babies (19; 58%) of gestational age > or = 27 weeks had increased survival compared to those < 27 weeks, (1; 7%; p = 0.001) and babies weighing > or = 750 g had increased survival (17, 65%) compared to those weighing < 750 g, (3, 14%; p < 0.001). Infants delivered by Caesarean section had improved survival 15 (58%) over those delivered vaginally (5, 24%; p = 0.02). All six (100%) infants whose mothers did not receive prenatal steroids died while 18 (50%) infants whose mothers received prenatal steroids died (p = 0.02). Significant factors associated with outcome were offered and gender was entered into a multiple regression model; gestational age and female gender remained independent predictors of survival. CONCLUSION: Obstetric measures for the prevention of preterm delivery need to be optimized in order to decrease the morbidity and mortality associated with extremely low birthweight infants.     

Influence of fluctuations of plasma large neutral amino acids with normal diets on the clinical response to levodopa.

Plasma large neutral amino acids (LNAAs) compete with levodopa for entry into the brain. Fluctuations in plasma LNAA concentrations could therefore contribute to variability in clinical response to levodopa. The hourly plasma levodopa, plasma LNAAs and clinical response were investigated in 11 fluctuating Parkinsonian patients on a regular hospital diet. The fluctuations in plasma levodopa were 2 to 3 times greater than the fluctuations of plasma LNAAs. The correlation between clinical response and plasma levodopa was substantially improved in only one patient by considering plasma LNAAs and calculating relative levodopa flux into brain. Although plasma LNAAs significantly increased during the day, the patients' clinical status did not uniformly deteriorate and mean afternoon clinical scores correlated better with mean plasma levodopa and levodopa flux than with mean plasma LNAAs. Minimum effective concentrations of levodopa for clinical response did not correlate with 9 am LNAA concentrations. It is concluded that in most patients, the relatively small variation in plasma LNAAs in comparison with the large variations in plasma levodopa indicates that fluctuations in LNAA are not an important contributor to the fluctuating response to levodopa.     

Depletion of essential elements by calcium disodium EDTA treatment in the dog.

The effect(s) of calcium disodium ethylenediaminetetraacetate (CaNa2EDTA) on the metabolism of Zn, Cu and Mn was investigated in mongrel female dogs. Dogs received either CaNa2EDTA (0.75 mmol/kg subcutaneously) or 0.9% NaCl (controls). Urine was collected every 6 h. Tissue samples were obtained from liver, kidney, duodenum, muscle, hair, skin and bone post exsanguination. CaNa2EDTA treatment increased urinary excretion of Zn, Cu and Mn, significantly when compared to controls (P less than 0.05, n = 5). Furthermore, CaNa2EDTA either decreased Zn levels (hair, duodenum, skin) and Mn levels (hair) or increased Cu levels in kidneys (P less than 0.05). These data suggest that the sustained urinary loss of Zn, Cu and Mn was probably associated, in part, with mobilization and redistribution of these essential elements from storage tissues as well as soft tissues. It was concluded that the use of calcium disodium EDTA for the management of heavy metal poisoning in dogs could adversely affect the metabolism of essential elements, particularly Zn, Cu and Mn.     

The calcium ionophore A23187 stimulates glycoprotein secretion by the guinea pig gallbladder

The purpose of this study was to examine the role of calcium ions in gallbladder glycoprotein secretion in cultured guinea pig gallbladder explants. The calcium ionophore A23187 showed a threshold of 2 micrograms per ml medium for stimulation of secretion of [3H]glucosamine-labeled glycoproteins over a 30 min incubation period. The ionophore at 3 and 5 micrograms per ml medium resulted in a 3- to 4-fold increase in secretion of [3H]glucosamine-labeled glycoproteins. Ionophore-induced stimulation of glycoprotein secretion was abolished by the addition of 0.01 mM verapamil to the medium. To study the effect of changes in extracellular calcium on basal glycoprotein secretion, explants were cultured for 24 hr in media with 0.007, 0.5 or 2.0 mM calcium; no differences in basal glycoprotein secretion were observed. When cultured in medium with 1.0 mM EGTA, basal secretion decreased significantly vs. controls in 0.007 mM total calcium medium. Total [3H]glucosamine incorporation by explants in medium with EGTA was unaltered, however, suggesting that the low level of calcium in the medium was selectively impairing the secretory process. These findings indicate that calcium ions are important in the regulation of gallbladder glycoprotein secretion.