Neuroprotective effects of progesterone in traumatic brain injury: blunted in vivo neutrophil activation at the blood-brain barrier

Background

Progesterone (PRO) may confer a survival advantage in traumatic brain injury (TBI) by reducing cerebral edema. We hypothesized that PRO reduces edema by blocking polymorphonuclear (PMN) interactions with endothelium (EC) in the blood-brain barrier (BBB).

Methods

CD1 mice received repeated PRO (16 mg/kg intraperitoneally) or vehicle (cyclodextrin) for 36 hours after TBI. Sham animals underwent craniotomy without TBI. The modified Neurological Severity Score graded neurologic recovery. A second craniotomy allowed in vivo observation of pial EC/PMN interactions and vascular macromolecule leakage. Wet/dry ratios assessed cerebral edema.

Results

Compared with the vehicle, PRO reduced subjective cerebral swelling (2.9 ± .1 vs 1.2 ± .1, P < .001), PMN rolling (95 ± 1.8 vs 57 ± 2.0 cells/100 μm/min, P < .001), total EC/PMN adhesion (2.0 ± .4 vs .8 ± .1 PMN/100 μm, P < .01), and vascular permeability (51.8% ± 4.9% vs 27.1% ± 4.6%, P < .01). TBI groups had similar a Neurological Severity Score and cerebral wet/dry ratios (P > .05).

Conclusions

PRO reduces live pericontusional EC/PMN and BBB macromolecular leakage after TBI. Direct PRO effects on the microcirculation warrant further investigation.     

Association between genetic variations in surfactant protein d and emphysema, interstitial pneumonia, and lung cancer in a Japanese population

Surfactant protein D (SFTPD) is a lung-specific anti-inflammatory factor that antagonizes inflammation by inhibiting oxidative stress and stimulating innate immunity. Variations in SFTPA2 and SFTPB, genes for other surfactant proteins, have been associated with lung cancer. We therefore investigated associations between SFTPD variations and lung cancer as well as emphysema and interstitial pneumonia, which are characterized by chronic inflammation from which lung cancer often arises. DNA from 1342 autopsy samples, including those from 140 subjects with lung cancer, was investigated. The single nucleotide polymorphism (SNP) rs721917, which results in methionine being exchanged for threonine at amino acid 11 (the Met11Thr variation), tended to be associated with emphysema and was associated with interstitial pneumonia and lung cancer. A haplotype analysis revealed that the haplotypes associated with emphysema and lung cancer differed from that associated with interstitial pneumonia, suggesting a differential role for SFTPD in the development of these diseases. A mediating analysis did not reveal a mediating effect exerted by emphysema or interstitial pneumonia on lung cancer. Our results suggested that SFTPD plays a role in the development of lung cancer and that the role for lung cancer may differ from that for interstitial pneumonia.     

Postural adjustment as a function of scene orientation

Visual orientation plays an important role in postural control, but the specific characteristics of postural response to orientation remain unknown. In this study, we investigated the relationship between postural response and the subjective visual vertical (SVV) as a function of scene orientation. We presented a virtual room including everyday objects through a head-mounted display and measured head tilt around the naso-occipital axis. The room orientation varied from 165° counterclockwise to 180° clockwise around the center of display in 15° increments. In a separate session, we also conducted a rod adjustment task to record the participant''s SVV in the tilted room. We applied a weighted vector sum model to head tilt and SVV error and obtained the weight of three visual cues to orientation: frame, horizon, and polarity. We found significant contributions for all visual cues to head tilt and SVV error. For SVV error, frame cues made the largest contribution, whereas polarity contribution made the smallest. For head tilt, there was no clear difference across visual cue types, although the order of contribution was similar to the SVV. These findings suggest that multiple visual cues to orientation are involved in postural control and imply different representations of vertical orientation across postural control and perception.     

Exogenous lipoid pneumonia following ingestion of liquid paraffin

An asymptomatic patient with exogenous lipoid pneumonia (ELP) due to silent aspiration of liquid paraffin ingested as a lubricant was diagnosed by bronchoalveolar lavage (BAL). BAL fluid separated into oily upper phase and lower aqueous phase spontaneously. Microscopic analysis of BAL cells revealed the presence of lipid-laden alveolar macrophages. Classic histochemical staining and electron microscope examination indicated that neutral lipid was dominant but phospholipid was also present in the lipid-laden macrophages. Together with the history of ingestion of liquid paraffin, we identified that the ingested liquid paraffin was the origin of the neutral lipid in the lipid-laden macrophages observed in the BAL fluid.     

Discrimination of histamine H1 and muscarinic receptor-mediated signalling pathways by phorbol ester in human astrocytoma cells

1. Histamine H1 receptor-mediated signalling was compared with muscarinic receptor-mediated signalling in 1321N1 human astrocytoma cells. 2. Short-term (2 min) treatment of cells with phorbol 12-myristate 13-acetate (PMA) resulted in a reduction of increases in intracellular Ca2+ ([Ca2+]i) induced by carbachol or histamine. 3. Carbachol-induced increases in [Ca2+]i were 10-fold more sensitive to PMA than the histamine-induced increases. 4. When cells were treated with PMA for 48 or 72 h (long-term treatment), protein kinase C (PKC) was down-regulated and PMA did not inhibit carbachol-induced increases in [Ca2+]i. 5. Histamine-induced increases in [Ca2+]i were significantly reduced by long-term treatment with PMA. 6. These findings suggest that the signalling pathways mediated by histamine H1 and muscarinic receptors can be distinguished by using PKC in 1321N1 human astrocytoma cells.     

Suppression of puerperal lactation by metergoline

Suppression of puerperal lactation by a potent serotonin antagonist, metergoline was studied in 33 puerperal women, i.e., abortion after sixteen weeks of gestation 6, premature labor 13, labor at term 13, and hydatiform mole 1. The drug was administered orally at a dose of 4 mg bid for 5 days to 26 subjects, starting within one week from delivery (group A). The remaining 7 subjects received 4 mg of metergoline bid for 7 days after more than 2 weeks from delivery (group B). Lactation was either rapidly suppressed or prevented in 22 out of the 26 subjects in group A and in all subjects in group B. After the therapy was stopped, rebound phenomena were observed in 4 subjects in group A and in 2 subjects in group B, but a further 5-7 days' treatment with metergoline produced satisfactory results. The mean plasma prolactin levels, studied in 10 subjects in group A at hourly intervals after the first metergoline dose, decreased significantly one hour later (p less than 0.05) and reached the nadir level, 19.9 +/- 2.6% of the mean basal value, 4 hours later. The daily plasma prolactin levels in 9 subjects were significantly lower than those of the control group during metergoline treatment (p less than 0.001). No side effects of metergoline medication were observed. Metergoline for a short course of administration is very effective in the suppression of puerperal lactation. In case of the suppression of lactation after the second week of puerperium, 10-14 days of metergoline treatment is recommended to avoid the rebound phenomena.     

Rapid and simple determination of epoxyeicosatrienoic acids in rabbit renal artery by reversed-phase HPLC with fluorescence detection

A liquid chromatographic method with fluorescence detection coupled with a solid-phase extraction was applied to the rapid determination of epoxyeicosatrienoic acids (EETs) in the rabbit renal artery. The EETs were extracted with an acetonitrile from renal artery homogenate and concentrated by a solid-phase extraction method. The concentrated EETs were reacted directly with a 6, 7-dimethoxy-1-methyl-2 (1H)-quinoxalinone-3-propionyl-carboxylic acid (DMEQ) hydrazide and separated by a reversed-phase HPLC with eluting a combination of a step-wise and a gradient of a mixture of methanol and water. The content of EETs in the renal arteries was significantly greater in the 0.5% cholesterol fed rabbits than in control rabbits. It is suggested that hyperchlesterolemia increases the production of EETs in the rabbit renal artery.