Effect of 2 ppm ozone exposure on rat lung lipid fatty acids

Based on in vitro studies, the initial damage to lung cells by ozone exposure is believed to result in part from the breakdown of lipid polyunsaturated fatty acids to aldehydes, ozonides, and peroxides. The present study measured lipid breakdown products in lungs isolated from rats pretreated with [1-14C]acetate 12 h before exposure for 4 h to either air or 2 ppm ozone. Lipid fatty acid breakdown was indicated by a 112% increase in thiobarbituric acid-reactive substances on ozone exposure and by changes in chemical and radioactive measurements of mono- and dicarboxylic acids formed by treatment of lipid fractions with hydrogen peroxide. Ozone exposure resulted in a 63% increase in recovery of short-chain fatty acids accounted for by increased recoveries of malonic acid by 37%, hexanoic acid by 47%, nonanoic acid by 118%, and azelaic acid by 107%. Recovery of glutaric acid was enhanced 15-fold by ozone exposure. Although decreases in tissue arachidonic acid could not be detected, oleic acid was significantly decreased by 36%. Recovery of radiolabel as short-chain fatty acids was increased by 65% on ozone exposure and was mainly accounted for by enhanced labeling of nonanoic and glutaric acid fractions. The failure to observe significant increases in 14C recovery in the other fractions suggested ozone-induced breakdown of unlabeled fatty acids. These results demonstrate the cleavage of unsaturated fatty acid double bonds following in vivo exposure of lungs to ozone. Breakdown of arachidonic and oleic acids was specifically identified by increased recoveries of glutaric and nonanoic acids, respectively.     

Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Adaptation of a perfused rat hemidiaphragm preparation to the study of intermediary metabolism

Glucose catabolism of a vascular perfused rat hemidiaphragm was determined at rest and during stimulation of the phrenic nerve with trains of either 5 (T5) or 15 (T15) pulses (20 msec intervals) per second. Tissues were perfused and bathed in HEPES-buffered medium containing 11 mM D-[U-14C, 5-3H]glucose, equilibrated with 100% O2. Resting glucose catabolism via the Emden-Meyerhof pathway was indicated by a 3H2O production rate per hemidiaphragm of 1.45 +/- 0.07 mumol/h, of which 47% was recovered as [14C]lactate with the remainder assumed to be metabolised by mitochondria. During the first 30 min of T5 and T15 stimulation, peak isometric tension declined from an initial value of 105 +/- 8 g by 54% and 79%, respectively. The resulting peak tensions of 48 and 22 g remained constant for the next 60 min. These tensions were associated with linear rates of 3H2O production of 2.93 +/- 0.41 and 2.84 +/- 0.25 mumol/h. Stimulation by T5 and T15 increased mitochondrial metabolism of glucose by 64% and 95%, respectively, with no significant alterations in lactate formation from either exogenous or endogenous sources. The results suggest that the initial decline in tension is due to fatigue of the fast anaerobic myofibers; whereas, the sustained force beyond 30 min is attributable to the mitochondrial-rich slow myofibers.     

Interferon-induced depressive illness in hep C patients responds to SSRI antidepressant treatments

This paper examines the role of selective serotonin reuptake inhibitors (SSRIs) in the treatment of hepatitis-C virus (HCV) patients who have developed interferon-α induced depression. A 2-year data analysis of HCV psychiatric liaison clinic has been undertaken. The diagnosis, treatment, and progress of those patients who were treated with interferon-α (INF-α) are reported. 53 of the 78 patients enrolled at the HCV Clinic and treated with INF-α were referred for psychiatric consultation. Six patients developed major depressive illness following INF therapy. They were all treated with SSRIs and they made full recovery. This is a significant observation and is concordant with other studies. Its biochemical ramifications are presented. It is concluded that INF-induced depression is fully reversible. A hypothesis is proposed that SSRIs modulate the neuro-protective neurotoxic ratio by possibly inhibiting the indole-2,3-dioxygenase induction of the kynurenine pathway.     

Imaging of thoracic aortic dissection

Acute thoracic aortic dissection has a high mortality if untreated, so the diagnosis must be rapidly made if mortality is to be lowered significantly. Multiple imaging techniques are often used. This retrospective study from 1988 to 1993 assesses the usefulness in diagnosis of chest X-rays, computed tomography (CT) scanning, aortography, magnetic resonance imaging (MRI), trans-thoracic (TTE) and trans-oesophageal (TOE) echocardiography. Forty-two patients with a final clinical diagnosis of dissection were studied. The diagnosis was confirmed in 16 (13 at surgery and three at autopsy). Three died with dissection given as the only cause for death. Chest X-ray abnormalities were seen in all 19 patients with surgery or death from dissection, with a widened mediastinum and/or dilated aorta being present in 17. In the group of 16 patients with surgery or autopsy proof, CT scans found dissections in 9 of 12 patients studied and correctly classified the type in only five. Aortography was performed in five, with accurate depiction of dissection and type in all. TTE found dissections in three of eight patients imaged by this method. MRI and TOE were performed each on two patients, with accurate depiction of dissection and type in each. Because of the relatively low sensitivity of CT scanning in defining aortic dissections Westmead Hospital is currently assessing the use of TOE as the prime imaging modality prior to surgical intervention.     

Luxatio erecta: the inferior glenohumeral dislocation

Luxatio erecta, or inferior glenohumeral dislocation, is a rare shoulder dislocation usually caused by a hyperabduction injury to the arm. We have reviewed the literature consisting of 80 cases of luxatio erecta and also discuss six additional cases that we have treated. The literature shows that either a fracture of the greater tuberosity or a rotator cuff tear was associated with this injury in 80% of patients; 60% of the patients reviewed sustained some degree of neurologic compromise, most commonly to the axillary nerve. These injuries usually resolved; the time for recovery varied from 2 weeks to 1 year. Only 3.3% of the cases demonstrated significant vascular compromise, but this is the highest incidence for any shoulder dislocation. Doppler studies of the affected arm or observation of the patient overnight are recommended because of the potentially disastrous complications of vascular insufficiency. If there is any indication of a vascular problem, immediate arteriogram is indicated. Although usually fairly easily reduced by overhead traction, the lesion is so rare that few physicians are familiar with the technique of reduction. Fluoroscopy was used in our most recent cases and was helpful in obtaining a complete and safe reduction.     

Nerve injury in athletes caused by cryotherapy

Cryotherapy is a therapeutic modality frequently used in the treatment of athletic injuries. In very rare circumstances, inappropriate use in some individuals can lead to nerve injury resulting in temporary or permanent disability of the athlete. Six cases of cold-induced peripheral nerve injury from 1988 to 1991 at the Sports Medicine Center at Duke University are reported. Although disability can be severe and can render an athlete unable to compete for several months, each of these cases resolved spontaneously. Whereas the application of this modality is typically quite safe and beneficial, clinicians must be aware of the location of major peripheral nerves, the thickness of the overlying subcutaneous fat, the method of application (with inherent or additional compression), the duration of tissue cooling, and the possible cryotherapy sensibility of some individuals.     

Results of a high-resolution genome screen of 437 Alzheimer's disease families

Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon 4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease. We performed a 9 cM genome screen of 437 families with AD, the full National Institute of Mental Health (NIMH) sample, which has been carefully ascertained, evaluated and followed by our group over the last decade. Performing standard parametric and non-parametric linkage analyses, we observed a 'highly significant' linkage peak by Lander and Kruglyak criteria on chromosome 19q13, which probably represents APOE. Twelve additional locations-on 1q23, 3p26, 4q32, 5p14, 6p21, 6q27, 9q22, 10q24, 11q25, 14q22, 15q26 and 21q22-met criteria for 'suggestive' linkage [i.e. two-point lod score (TLS) >/=1.9 and/or multipoint lod score (MLS) >/=2.2] in at least one of our analyses. Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD.