Tissue distribution of synthetic heme analogues: studies with tin, chromium, and zinc mesoporphyrins.

The uptake in tissue of Sn-mesoporphyrin (SnMP), Cr-mesoporphyrin (CrMP) and Zn-mesoporphyrin (ZnMP) administered at doses ranging from 1 to 10 mu mol/kg BW and the effects of these compounds on heme oxygenase activity were examined in both adult and neonatal rats. SnMP and CrMP, but not ZnMP, were rapidly cleared from blood and taken up by liver, spleen and kidney where marked inhibition of heme oxygenase activity was demonstrated. None of the metalloporphyrins were detectable in brain, and no inhibition of heme oxygenase activity was demonstrable in this tissue after administration of the compounds to both adult and neonatal rats.

Effects of a series of metalloporphyrins on adrenal, testicular and thyroid function in rats.

We have extended our earlier studies [Pharmacology 1986;34:9-16] on the effects of certain synthetic heme analogues and cobalt chloride (CoCl2) on endocrine functions mediated by the hypothalamic-pituitary axis to examine specifically the ability of Sn-protoporphyrin (SnPP) and Sn-mesoporphyrin (SnMP) to perturb adrenal, testicular and thyroid function since there is interest in the use of Sn(tin)-porphyrins in the treatment of hyperbilirubinemia of the newborn. SnPP and SnMP when administered to adult male rats did not alter serum corticosterone, testosterone, thyroxine or triiodothyronine levels when compared to control animals. In addition, administration of exogenous adrenocorticotrophic hormone produced an increase in serum corticosterone levels that was comparable in placebo-treated and SnPP- and SnMP-treated animals.

Changes in chest wall compartment volumes on induction of anaesthesia with eltanolone, propofol and thiopentone.

Changes in the expiratory dimensions of the rib cage and abdomen on induction of anaesthesia with eltanolone, propofol and thiopentone were measured in 76 patients using respiratory inductance bands. Calibration of the respiratory inductance plethysmograph was by simultaneous flow measurement with a pneumotachograph. Movement of the vertebral column was restrained with a rigid mattress to allow volume change to be estimated more accurately from rib cage and abdominal dimensions.

Influence of oral clonidine on the ventilatory response to acute and sustained isocapnic hypoxia in human males.

Animal studies suggest that alpha 2 agonists inhibit the chemoreceptor response to hypoxia. We have examined the effect of oral clonidine on the ventilatory response to sustained, isocapnic hypoxia (SpO2 79.7% (SD 1.

Downregulation of the human heme oxygenase gene by glucocorticoids and identification of 56b regulatory elements.

Several human heme oxygenase-1 promoter-driven chloramphenicol acetyltransferase constructs were examined in order to analyze promoter activity of the heme oxygenase-1 gene in microvessel endothelial cells. Heme oxygenase promoter activity was up-regulated by interleukin-6. This induction was shown to be down-regulated by glucocorticoids.

Endothelium-dependent relaxation to the B1 kinin receptor agonist des-Arg9-bradykinin in human coronary arteries.

Des-Arg9-bradykinin (des-Arg9-BK) caused endothelium-dependent relaxations in human, isolated coronary arteries which upregulated with in vitro incubation time. Relaxations to des-Arg9-BK were inhibited by the B1 receptor antagonist, des-Arg9-[Leu3]-BK (pK(B), 6.14 +/- 0.

Changes in blood volume distribution between legs and trunk during halothane anaesthesia.

To assess the influence of halothane anaesthesia on the distribution of blood volume in supine humans, we used albumin labelled with 99mTc to measure blood volume distribution along the craniocaudal axis. We studied 6 volunteers in the supine position before, during and after anaesthesia with 1% halothane and 66% nitrous oxide. Using collimated detectors above and below the subject, counts were obtained from the legs, pelvis, abdomen, rib cage and head, with the arms excluded.

Relationship of admission thyroid function tests to outcome in critical illness.

One hundred and eighty patients had serum thyrotropin, total triiodothyronine and free thyroxine concentrations measured within 3 h of admission to the Intensive Therapy Unit to assess whether thyroid function tests could predict outcome in critical illness. Overall mortality was 30.6%.

Endothelium-dependent relaxations mediated by inducible B1 and constitutive B2 kinin receptors in the bovine isolated coronary artery.

1. Rings of bovine left anterior descending coronary artery (LAD) were contracted with the thromboxane A2-mimetic, U46619 (1-30 nM), to approximately 40% of their maximum contraction to 125 mM KCl Krebs solution (KPSSmax) for comparison of responses to the B1 and B2 kinin receptor agonists, des-Arg9-bradykinin (des-Arg9-BK) and bradykinin (BK), respectively. Relaxation responses were normalized as percentages of the initial U46619-induced contraction level, while contractile responses were expressed as percentages of KPSSmax.

Depletion of cytochrome P-450 by thyroid hormone and cobalt-protoporphyrin IX in rat liver: evidence that susceptibility varies among forms of the heme protein.

The ability of 3,5,3'-triiodothyronine (T3) and cobalt-protoporphyrin LX (CoPP) to alter the levels of the cytochrome P-450 isoforms, CYP3A2, CYP2E1, CYP2B1 and CYP2B2, was examined in vitro in thyroidectomized adult male rats. With the exception of CYP2B2, CoPP administration resulted in a decline in each of the cytochrome P450 isoforms examined. The effects of T3 administration on immunoreactive levels of cytochrome P-450 were also examined in the liver of thyroidectomized rats.

Does sleep enhance the effect of subanesthetic isoflurane on hypoxic ventilation?

After surgery, patients may receive little audiovisual stimulation and may sleep. Lack of audiovisual stimulation enhances the suppression of the hypoxic ventilatory response (HVR) by 0.1 minimum alveolar anesthetic concentration (MAC) isoflurane.

Biological variation and the effect of fasting and halothane anesthesia on plasma glutathione S-transferase concentrations.

Using a specific RIA, we have investigated in patients and volunteers whether fasting, diminished hepatic clearance, hemoconcentration, or within-day biological variation might be responsible for the transient increases in plasma glutathione S-transferase (GST) concentration observed after anesthesia. GST concentration was measured in 44 healthy volunteers after an overnight fast and at 3, 6, and 24 h after the fasting sample. The concentration was significantly lower at 3 and 6 h after than in the fasting sample (P = 0.

Direct comparison of Sn-mesoporphyrin, an inhibitor of bilirubin production, and phototherapy in controlling hyperbilirubinemia in term and near-term newborns.

Background: Sn-mesoporphyrin (SnMP) is a potent inhibitor of bilirubin production. In our previous studies a single dose (6 mumol/kg birth weight) significantly moderated hyperbilirubinemia and reduced phototherapy (PT) time by > 75% when administered within 24 hours of birth to preterm infants.

Objective: To directly compare the efficacy of SnMP and PT for controlling hyperbilirubinemia in term and near-term infants.

Interaction of the effects of domperidone and sub-anaesthetic concentrations of isoflurane on the immediate and sustained hypoxic ventilatory response in humans.

Twenty normal male subjects with brisk hypoxic ventilatory responses were recruited and ventilatory responses to sustained isocapnic hypoxia (SaO2 80.4 (SD 1.3)% for 20 min) were studied on separate days under four conditions: hypoxia alone, with or without domperidone, and 0.

Changes in end-expiratory lung volume on induction of anaesthesia with thiopentone or propofol.

To determine the effects of induction agent and obesity on the change in functional residual capacity caused by induction of anaesthesia, we measured the change in end-expiratory respiratory volume (EERV) during induction of anaesthesia with either thiopentone or propofol. Female patients breathed via a face mask from a closed circle system connected to a water spirometer. The spirometer tracing was used to measure the decrease in EERV.

Management of monocular cataract with long-term dilation in children.

We describe the use of long-term dilation and patching therapy in the management of three cases of pediatric monocular cataract. The cataracts were felt to be visually significant in the undilated state but consistent with good formed vision in the dilated state. One patient had a congenital cataract managed from 4 weeks of life, and two patients had late diagnosed cataracts of indeterminate onset presenting with dense deprivation amblyopia.

Change in chest wall dimensions on induction of anaesthesia: a reappraisal.

We used a linearized magnetometer to measure the changes in rib cage and abdominal dimensions which occurred during induction of anaesthesia with i.v. methohexitone when spinal movement was prevented.