Effects of anterior pituitary hormones on hepatic corticosterone metabolism in rats

Experiments were conducted to determine the effects of anterior pituitary hormones on hepatic corticosterone metabolism in rats. Hypophysectomy lowered A-ring reduction but did not affect sidechain metabolism. Administration of prolactin, FSH, LH or FSH + LH to hypophysectomized rats affected neither process. Similarly, ACTH or growth hormone, when given alone, did not affect corticosterone metabolism. However, combined treatment with ACTH and growth hormone significantly reduced the rate of ring A metabolism, suggesting that hormonal interactions may be important in the control of hepatic steroid metabolism.     

Degenerate PCR primers for the amplification of fragments from genes encoding response regulators from a range of pathogenic bacteria

Many bacterial responses to environmental stimuli are mediated by response regulators which coordinately regulate genes involved in particular adaptive responses. Degenerate oligonucleotide primers were used to amplify by the polymerase chain reaction (PCR), fragments from genes encoding eleven novel response regulators. Sequence and phylogenetic analysis revealed that phoB, phoP and creB gene fragments had been amplified from Yersinia enterocolitica and Yersinia pseudotuberculosis, and that a creB sequence had been amplified from Campylobacter jejuni. Four amplified fragments from C. jejuni, Listeria monocytogenes, Mycobacterium tuberculosis and Escherichia coli clearly came from response regulator genes, but were not closely related to any of the known genes. Mutagenesis of the newly identified genes should allow us to determine their function and the genes under their control.     

Usual Interstitial Pneumonia Preceding Collagen Vascular Disease: A Retrospective Case Control Study of Patients Initially Diagnosed with Idiopathic Pulmonary Fibrosis

Background

The aim of this study was to evaluate the cumulative incidence and the predictive factors for collagen vascular disease (CVD) in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF), and to examine the features of patients who then developed CVD.

Methods

This was a retrospective review of 111 consecutive patients with IPF diagnosed at our institution. None of the patients fulfilled any of the CVD criteria from the American College of Rheumatology (ACR) within 6 months or more after the diagnosis of IPF.

Results

Ten patients (9.0%) developed CVD during the follow-up period: four had rheumatoid arthritis (RA); four had microscopic polyangiitis (MPA); one had systemic sclerosis (SSc); and one had SSc and Sjogren’s syndrome (SjS). The mean time until CVD diagnosis was 3.9 years. The cumulative incidences of CVD at 1, 5, and 10 years were 0.91%, 9.85%, and 15.5%, respectively. Patients who developed CVD were significantly younger, more likely to be women and had a better prognosis than those with IPF. Cox proportional hazards regression analysis showed that female sex and the presence of lymphoid aggregates with germinal centers were significantly associated with the occurrence of CVD in patients initially diagnosed with IPF.

Conclusions

CVD is an important underlying condition in IPF, and shows better prognosis. The possibility of the development of CVD should remain a consideration in the follow-up of IPF.     

Levofloxacin cures experimental pneumonic plague in African green monkeys

Background

Yersinia pestis, the agent of plague, is considered a potential bioweapon due to rapid lethality when delivered as an aerosol. Levofloxacin was tested for primary pneumonic plague treatment in a nonhuman primate model mimicking human disease.

Methods and Results

Twenty-four African Green monkeys (AGMs, Chlorocebus aethiops) were challenged via head-only aerosol inhalation with 3–145 (mean = 65) 50% lethal (LD₅₀) doses of Y. pestis strain CO92. Telemetered body temperature >39°C initiated intravenous infusions to seven 5% dextrose controls or 17 levofloxacin treated animals. Levofloxacin was administered as a “humanized” dose regimen of alternating 8 mg/kg and 2 mg/kg 30-min infusions every 24-h, continuing until animal death or 20 total infusions, followed by 14 days of observation. Fever appeared at 53–165 h and radiographs found multilobar pneumonia in all exposed animals. All control animals died of severe pneumonic plague within five days of aerosol exposure. All 16 animals infused with levofloxacin for 10 days survived. Levofloxacin treatment abolished bacteremia within 24 h in animals with confirmed pre-infusion bacteremia, and reduced tachypnea and leukocytosis but not fever during the first 2 days of infusions.

Conclusion

Levofloxacin cures established pneumonic plague when treatment is initiated after the onset of fever in the lethal aerosol-challenged AGM nonhuman primate model, and can be considered for treatment of other forms of plague. Levofloxacin may also be considered for primary presumptive-use, multi-agent antibiotic in bioterrorism events prior to identification of the pathogen.