Central Deficiency of Corticotropin-Releasing Hormone Receptor Type 1 (CRH-R1) Abolishes Effects of CRH on NREM But Not on REM Sleep in Mice

Study Objectives:

Corticotropin-releasing hormone (CRH) is the major activator of the hypothalamic-pituitary-adrenocortical (HPA) system and orchestrates the neuroendocrine, autonomous as well as behavioral responses to stress. Many studies suggest an influence of CRH on sleep-wake regulation even in the absence of stressors. However, none of these studies yet clearly distinguished between central and peripheral effects of CRH. Therefore, we investigated in CNS-specific CRH receptor type 1 deficient mice whether centrally administered CRH could induce its sleep-wake modulatory effects without peripheral induction of HPA activity.

Design:

Male mice (C57BL/6J, CNS-specific CRH-R1 knockout [CKO] mice and their control littermates [CL]) were intracerebroventricularily (i.c.v.) injected with vehicle or 3 different doses of CRH shortly before the beginning of the light period. Electroencephalogram (EEG) and electromyogram (EMG) were monitored to compare the effects of CRH on vigilance states with or without presence of central CRH-R1. To quantify HPA-axis reactivity to CRH injections in CKO and CL animals, blood samples were analyzed to determine plasma corticosterone concentrations.

Results:

I.c.v. injections of CRH promoted wakefulness while decreasing NREMS in C57BL/6J and CRH-R1 CL animals, whereas such changes were not exerted in CKO mice. However, REMS suppression after CRH application persisted in all animals. I.c.v. injected CRH increased plasma corticosterone levels in both CL and CKO mice.

Conclusions:

The results demonstrated that CRH has a major impact on wake and NREMS regulation which is predominantly mediated through central CRH-R1. Peripheral actions of CRH, i.e., elevated HPA activity, may interfere with its central effects on REMS but not on NREMS suppression.

Citation:

Romanowski CPN; Fenzl T; Flachskamm C; Wurst W; Holsboer F; Deussing JM; Kimura M. Central deficiency of corticotropin-releasing hormone receptor type 1 (CRH-R1) abolishes effects of CRH on NREM but not on REM sleep in mice.SLEEP 2010;33(4):427-436.     

Solitary pulmonary metastasis from intracranial meningiothelial meningioma

Although known, histologically proven pulmonary metastasis from a benign intracranial meningioma is exceedingly rare. We report a case of meningiothelial meningioma producing a solitary pulmonary deposit.     

Fetal iron status in maternal anemia

Hemoglobin, serum iron, transferrin saturation and ferritin were measured on paired maternal and cord blood samples in 54 anemic (hemoglobin < 110 g/L) and 22 non-anemic (hemoglobin ≥ 110 g/L) pregnant women at term gestation. The levels of hemoglobin, serum iron, transferrin saturation and ferritin were significantly low in the cord blood of anemic women, suggesting that iron supply to the fetus was reduced in maternal anemia. The linear relationships of these parameters with both maternal hemoglobin and maternal serum ferritin indicated that the fetus extracted iron in amounts proportional to the levels available in the mother. Infants of mothers with moderate and severe anemia had significantly lower cord serum ferritin levels and hence poor iron stores at birth. It is concluded that iron deficiency anemia during pregnancy adversely affects the iron endowment of the infant at birth.     

棉酚对体外家兔精子顶体酶类的抑制作用

本文对棉酚体外抑制１０种家兔精子顶体酶活性进行了测定。当醋酸棉酚浓度为１２～７６μｍｏｌ／Ｌ时，可完全或明显抑制顶体酶（ａｃｒｏｓｉｎ）、Ａｚｏｃｏｌｌ蛋白酶、芳香基硫酸酯酶和神经氨酸苷酶活性；而当浓度高达３８０μｍｏｌ／Ｌ时才能抑制透明质酸酶、β－葡糖苷酸酶和酸性磷酸酶，但不抑制磷酸酯酶Ｃ、碱性磷酸；酶和β－Ｎ－乙酰氨基葡糖苷酶。棉酚对芳香基硫酸酯酶的抑制作用是一种非竞争性抑制作用，Ｋｉ为１２０μｍｏｌ／Ｌ。其抑制作用是可逆的，呈剂量依赖关系。由于抑制家兔精子顶体酶所需棉酚浓度比精子糖酵解或能量代谢酶要低，因此，这些敏感酶似可作为监护棉酚引起不育的指标。     

Does intramuscular vitamin K1 act as an unintended depot preparation?

Objective : To propose a hypothesis that the long duration of effect of intramuscular (i.m.) vitamin K₁ in preventing late onset haemorrhagic disease results from a depot effect after i.m. injection.
Methodology : Review of scientific literature relating to the pharmacology of vitamin K, and the aetiology of late onset haemorrhagic disease.
Results : A single i.m. dose of vitamin K₁ is effective for at least 2 months, whereas the duration of effect of a single oral dose is about 3-4 weeks. The known pharmacological properties of vitamin K₁ are seemingly at variance with the long duration of effect of an i.m. dose. Menaquinones (vitamins K₂) are absent in the newborn liver, but gradually accumulate after birth. This, together with the low concentrations of vitamin K₁ in human breast milk, may explain the peak frequency of late onset haemorrhagic disease at 4-8 weeks. We hypothesize that after i.m. injection, vitamin K₁ acts as a depot preparation by forming a viscous mass in muscle tissue which is slowly absorbed over many weeks. This hypothesis is supported by reports indicating significantly higher plasma vitamin K₁ levels several weeks after i.m., as compared to oral vitamin K₁.
Conclusions : The prolonged efficacy of i.m. vitamin K₁, compared to oral preparations may be due to a depot effect New oral preparations of vitamin K₁, despite greatly improved bioavailability, may have a shorter duration of effect than i.m. vitamin K₁, and therefore be less effective for long-term prophylaxis.     

Routine microbiological testing in sudden and unexpected infant death

Objective : To evaluate the significance of microbiological test results in a series of infants who had died suddenly and unexpectedly.
Methodology : Following a review of all cases of sudden natural death in infants presenting to the Adelaide Children's Hospital (ACH) division of the Women's and Children's Hospital (WCH) over the 10 year period between 1983 and 1992, specific evaluation of microbiological test results was undertaken.
Results : There were 329 cases of sudden infant death syndrome (SIDS) and 23 cases in which sudden infant death was either attributed to other conditions or was unclassifiable. Positive microbiological results were recorded in the majority of cases, most being considered to be due to postmortem overgrowth or to contamination at autopsy. Of the remaining cases, microbiological results were essential to the establishment of the diagnosis in three cases, and were a useful adjunct to the diagnosis in a further six cases.
Conclusions : Routine microbiological testing in cases presenting as SIDS did not reveal occult sepsis in most instances. Such testing did, however, add support to the diagnosis of SIDS where no pathogens were isolated and, if not undertaken, would have resulted in a small percentage of cases of sudden infant death due to infections remaining undiagnosed.     

Osteochondral allograft transplantation

Experience with fresh osteochondral allografting for cartilage defects in the knee now extends two decades. Clinical outcomes and basic scientific investigations have supported the theoretic basis for this procedure. At the University of California, San Diego, our experience has encouraged us to continue to offer this procedure as a primary treatment for both large and small articular cartilage defects in the young knee. The success rate of fresh osteochondral allografting, particularly in isolated femoral condylar defects, compares favorably with other presently available cartilage repair and resurfacing techniques. In our second hundred cases, which we are currently evaluating, failure of monopolar allografts has been exceedingly rare in short-term follow-up. Fresh osteochondral allografting also appears to be effective in treating larger osteochondral lesions, where there are few other attractive alternatives. Fresh osteochondral allografts can thus be used to treat a wide spectrum of articular pathology. Technical refinements, and improvement in our understanding of graft-host interaction, as well as chondrocyte biology, should continue to improve clinical results. Disadvantages of fresh osteochondral allografting include the relative paucity of donor tissue, complexities in procurement and handling, and the possibility of disease transmission through the transplantation of fresh tissue. At present, only institutions that have overcome these obstacles seem capable of routinely performing this type of articular cartilage transplantation. In the future, as tissue banking and cartilage storage technology advance, fresh allograft tissue may become more available, allowing more widespread use of fresh osteochondral allografting in the treatment of articular cartilage lesions.     

A three centre study of the variability of ankle foot orthoses due to fabrication and grade of polypropylene

This study investigates if fabrication techniques employed at different orthotic centres affect the characteristics of the manufactured plastic orthoses. Plaster models were formed from the same master mould. The thickness and bending stiffness of the supplied polypropylene sheets were measured prior to fabrication. An orthotic technician at each of the 3 orthotic centres manufactured 4 homopolymer and 4 copolymer polypropylene ankle-foot orthoses (AFOs), following each centre's fabrication practice. Another technician at one of the orthotic centres manufactured an additional 4 homopolymer and 4 copolymer AFOs. The thickness, the dorsiflexion stiffness and plantarflexion stiffness of the 32 fabricated AFOs were monitored and compared. Analysis of the results suggests: Copolymer polypropylene sheets are supplied marginally thicker than homopolymer polypropylene sheets. The difference between the thickness of the 16 copolymer and 16 homopolymer AFOs was not significant. The thickness of the AFOs manufactured in copolymer was less consistent than homopolymer. Dorsiflexion stiffness of the copolymer AFOs was less consistent than homopolymer AFOs. Although the bending stiffness of the copolymer and homopolymer sheets differed significantly, there was no significant difference between the dorsiflexion stiffness of the copolymer and homopolymer AFOs. Plantarflexion stiffness was consistent for both the copolymer and the homopolymer AFOs and there was no significant difference between the plantarflexion stiffness of the copolymer and homopolymer AFOs. The thickness and flexural stiffness of the AFOs manufactured by 2 technicians at the same centre did not differ. These results are useful benchmarks for the flexural stiffness of AFOs.     

Treatment of post-traumatic ankle arthrosis with bipolar tibiotalar osteochondral shell allografts

We report on tibiotalar osteochondral shell allografts for post-traumatic ankle arthropathy in seven patients. Average follow-up was 148 months (range, 85 to 198). Patients were evaluated by a questionnaire, SF-12 survey, ankle score, physical exam and radiographs. The ankle score increased from 25 preoperatively to 43 at latest follow-up (maximum score 100). SF-12 scores increased from 30 to 38 (Physical Component) and 46 to 53 (Mental Component). The failure rate was 42%. Four of seven patients reported good or excellent results. Five patients stated they would undergo a similar procedure again. Complications included graft fragmentation, poor graft fit, graft subluxation, and non-union. Follow-up radiographs demonstrated joint space narrowing, osteophytes, and sclerosis, even in cases with excellent clinical status. Fresh osteochondral shell allografting may provide a viable alternative for the treatment of post-traumatic ankle arthrosis in selected individuals.