Effect of estrogens on bone marrow adipogenesis and Sirt1 in aging C57BL/6J mice

Age-related bone loss has been associated with high levels of marrow adipogenesis. Estrogens (E₂) are known to regulate the differentiation of marrow precursors into osteoblasts, however, their role in bone marrow adipogenesis remain unknown. E₂ regulate adipocyte differentiation in subcutaneous and visceral fat through interaction with other nuclear receptors. This interaction has not been assessed in bone marrow adipocytes in vivo. In this study, we compared two groups of animals, young and old, after either oophorectomy (OVX) or oophorectomy plus E₂ (OVX + E₂) replacement. We found that absence of E₂ was associated with higher levels of PPARγ and lower levels of Sirt1 most significantly in the old group. In addition, old mice responded better to E₂ replacement in terms of reducing adipogenesis and PPARγ expression as well as increasing levels of Sirt1 expression. Our findings represent a new understanding of the role of E₂ in age-related bone loss, which could be mediated through the regulation of Sirt1 expression within the bone marrow. In addition, this evidence suggests that old individuals may show a better response to E₂ administration in terms of reverting the high levels of marrow fat seen in age-related bone loss.     

Faecal occult blood test‐based screening programme with high compliance for colonoscopy has a strong clinical impact on colorectal cancer

Background:

The results of a pilot colorectal cancer screening programme by biennial immunochemical faecal occult blood test (FOBT) are reported.

Methods:

All residents aged between 50 and 69 years in the Italian province of Lecco were invited to have a FOBT. Those with a positive result were offered colonoscopy. FOBT uptake and compliance with colonoscopy were assessed. Detection rate and positive predictive value (PPV) for cancer and adenoma were calculated. Tumour stages were compared between screen‐detected cancers and other colorectal cancers diagnosed within the target age group.

Results:

Some 38 693 (49·6 per cent) of 78 083 individuals had a FOBT and 2392 (6·2 per cent) had a positive result. Colorectal cancer was diagnosed in 4·6 per cent and advanced adenoma in 32·7 per cent. PPVs were 4·0 per cent for cancer, 28·1 per cent for advanced adenoma and 36·6 per cent for any adenoma. There was a significant difference in incidence of stage III/IV disease between screened and non‐screened cohorts. Compliance for colonoscopy was 92·0 per cent. Major determinants of compliance were age less than 59 years, female sex, high education level and non‐manual work.

Conclusion:

These results justify extension of colorectal cancer screening to other regions of Italy. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Microanatomy and surgical approaches to the infratemporal fossa: an anaglyphic three-dimensional stereoscopic printing study.

Objective: The infratemporal fossa (ITF) is a continuation of the temporal fossa between the internal surface of the zygoma and the external surface of the temporal bone and greater wing of the sphenoid bone that is sitting deep to the ramus of the mandible. The principal structure to understanding its relationships is the lateral pterygoid muscle. Other important structures are the medial pterygoid muscle, the maxillary artery, the pterygoid venous plexus, the otic ganglion, the chorda tympani nerve and the mandibular nerve. In this study, we describe the microsurgical anatomy of the ITF, as viewed by step-by-step anatomical dissection and also through the perspective of three lateral approaches and one anterior surgical approach. Methods: Eight cadaver specimens were dissected. In one side of all specimens, an anatomical dissection was done in which a wide preauricular incision from the neck on the anterior border of the sternoclidomastoid muscle at the level of the cricoid cartilage to the superior temporal line was made. The flap was displaced anteriorly and the structures of the neck were dissected followed by a zygomatic osteotomy and dissection of the ITF structures. On the other side were the surgical approaches to the ITF. The combined infratemporal and posterior fossa approach was done in two specimens, the subtemporal preauricular infratemporal fossa approach in two, the zygomatic approach in two, and the lateral transantral maxillotomy in two. The anatomical dissections were documented on the three-dimensional (3D) anaglyphic method to produce stereoscopic prints. Results: The lateral pterygoid muscle is one of the principal structures to enable understanding of the relationships into the ITF. The tendon of the temporal muscle inserts in the coronoid process at the ITF. The maxillary artery is the terminal branch of the external carotid artery that originates at the neck of the mandible and runs into the parotid gland. In our dissections the maxillary artery was lateral to the buccal, lingual, and inferior alveolar nerves. We found the second part of the maxillary artery superficial to the lateral pterygoid muscle in all specimens The anterior and posterior branches of the deep temporal artery supply the temporal muscle. In two cases we found a middle deep temporal artery. The different approaches that we used provided different views of the same anatomical landmarks and this provides not only safer surgery but also the best choice to approach the ITF according with the pathology extension. Conclusions: The ITF is a complex region on the skull base that is affected by benign and malignant tumors. The study through different routes is helpful to disclose the relationship among the anatomical structures. Although the authors have shown four approaches, there are a variety of approaches and even a combination of these can be used. This type of anatomical knowledge is essential to choosing the best approach to treat lesions in this area.     

Calcium entry blockers and cardioplegia: interaction between nifedipine, potassium, and hypothermia

The potential additive protective effect provided by nifedipine to the University of Alabama Hospitals cardioplegia solution (ACS) was assessed with the use of a guinea pig heart-lung model of cardiopulmonary bypass and ischemic arrest. The addition of nifedipine consistently enhanced the protective properties of ACS infused at 37 degrees C; functional recovery was similar to that observed with cold ACS. Despite the additional protection under normothermic conditions, nifedipine did not improve recovery after infusion at 4 degrees C. The abolition by hypothermia of the protective effects of nifedipine suggests a similarity in action between nifedipine and hypothermic protection. The interaction between ACS and nifedipine was studied on bovine coronary arteries in vitro. Nifedipine caused a marked reduction in the coronary vasoconstricting effect of ACS, both under normothermic and hypothermic conditions. The use of nifedipine in cardioplegia may provide additional protection when uneven distribution of the cardioplegic solution is expected and hypothermic protection is unreliable.     

Adult rat seminiferous tubules secrete a fraction greater than 30 kDa to regulate spermatogenesis

The present study was designed to examine the effects of a >30kDa fraction of medium conditioned for 2 days by adult rat seminiferoustubules on inhibin secretion by cultured tubules, and on spermatogenesisand fertility of male rats. Inhibin secretion was assayed byadding the >30 kDa fraction to 5 cm segments of adult ratseminiferous tubules and measuring inhibin by radioimmunoassayat 2 day intervals. Fertility was assayed by injecting malerats daily for up to 45 days with the >30 kDa fraction andthen mating them with a proestrus female, or by injecting for15 days and mating them with two female rats. The assay usedto evaluate the in-vivo effect of the >30 kDa fraction onthe testis involved an assessment of frequencies of seminiferoustubule stages scored by transillumination on intact tubules.The addition of the >30 kDa fraction to the adult rat seminiferoustubules cultured for 2 days resulted in an inhibition of inhibinsecretion into the medium. This effect was reversed when thefraction was removed and changed with fresh medium and culturedfor a further 4 days. The >30 kDa fraction administered i.p.to adult male rats resulted in a low fertilization rate comparedto control rats (67%) (P < 0.05). The assessment of frequenciesof seminiferous tubule stages scored by transillumination showedan increased frequency of stage VI and decreased frequency ofstages VII and VIII after treatment. The results of the presentstudy provide additional evidence that local regulation of Sertolicell function is mediated by a >30 kDa component or componentssecreted by adult seminiferous tubules which could arrest spermatogenesis.