Delayed and persistent suppression of bronchoconstriction by trypsin in the airway lumen.

Mucosal trypsin, a protease-activated receptor (PAR) stimulant, may have an endogenous bronchoprotective role on airway smooth muscle. To test this possibility the effects of lumenal trypsin on airway tone in segments of pig bronchus were tested. Bronchial segments from pigs were mounted in an organ chamber containing Kreb's solution. Contractions were assessed from isovolumetric lumen pressure induced by acetylcholine (ACh) or carbachol added to the adventitia. Trypsin, added to the airway lumen (300 microg x mL(-1)), had no immediate effect on smooth muscle tone but suppressed ACh-induced contractions after 60 min, for at least 3 h. Synthetic activating peptides (AP) for PAR1, PAR2 or PAR3 were without effect, but PAR4 AP caused rapid, weak suppression of contractions. Lumenal thrombin was without effect and did not prevent the effects of trypsin. Effects of trypsin were reduced by N(omega)-nitro-L-arginine methyl ester but not indomethacin. Trypsin, thrombin and PAR4 AP released prostaglandin E2. Adventitially, trypsin, thrombin and PAR4 AP (but not PAR2 AP) relaxed carbachol-toned airways after <3 min. The findings of this study show that trypsin causes delayed and persistent bronchoprotection by interacting with airway cells accessible from the lumen. The signalling mechanism may involve nitric oxide synthase but not prostanoids or protease-activated receptors.     

Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on the pituitary-thyroid-axis.

The lack of estrogen during menopause is associated with various symptoms including osteoporosis, cardiovascular diseases, and menopausal symptoms. For many years, conventional hormone replacement therapy has been successfully used to treat these conditions. However, in light of recent studies that draw attention to potential hazards of conventional HRT, various attempts were undertaken to search for alternatives of classical HRT. Phytoestrogens are supposed to ameliorate various discomforts associated with menopause. Resveratrol (RES) is present in red wine, grapes and peanuts and has been implicated in cardioprotection and prevention of adverse side effects observed after regular HRT. As the pituitary-thyroid axis is a target of estrogen action, we first assessed the effects of E2 administration on thyroid hormone stimulating hormone releasing hormone (TRH)-induced thyroid stimulating hormone (TSH) secretion from pituitary cell cultures in vitro. Our data reveal that E2 treatment augments the TRH-induced TSH secretion. We furthermore designed a long-term study of three months to assess the effects of subcutaneous and oral administration of 17beta-estradiol (E2), as well as the actions of RES on the pituitary-thyroid axis in ovariectomized (OVX) female rats. Our results demonstrate that serum levels of 1.0 and 8.1 microM RES lead to a significant increase in total serum triiodthyronine (T3) levels. OVX induces TSHbeta mRNA in the adenohypohysis and E2 treatment attenuates this effect. Treatment of rats with subcutaneous implants of E2 does not affect the pituitary-thyroid axis, whereas orally applied E2 benzoate (E2B) increases plasma TSH and total thyroxine (T4) in OVX rats. In all animals, we could not detect changes in thyroid morphology as assessed by hematoxylin-eosin (HE) and Perjod-Acid Schiff's (PAS) staining.     

A clinical approach to the management of a patient with suspected renovascular disease who presents with leg ischemia.

Atherosclerotic renal artery stenosis (ARAS) may cause hypertension, progressive renal failure, and recurrent pulmonary edema. It typically occurs in high risk patients with coexistent vascular disease elsewhere. Most patients with ARAS are likely to die from coronary heart disease or stroke before end-stage renal failure occurs. Recent controlled trials have shown that most patients undergoing angioplasty to treat renovascular hypertension still need antihypertensive agents 6 or 12 months after the procedure. Nevertheless, the number of antihypertensive agents required to control blood pressure adequately is lower following angioplasty than for medication alone. Trials assessing the value of revascularization for preserving renal function or preventing clinical events are only in the early recruitment phase. Revascularization should be undertaken in patients with ARAS and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or with an increase in plasma creatinine levels during angiotensin-converting enzyme inhibition. With or without revascularization, medical therapy using antihypertensive, hypolipidemic and antiplatelet agents is necessary in almost all cases.     

Verletzungen der Handwurzel

A fall onto the hand can be followed by ligament ruptures, bone fractures or dislocated fractures of the carpus. The diagnosis is based on history, clinical evaluation, and X-ray examination in two perpendicular planes, followed if necessary by CT scan or MRI scan. Lesions of the scapholunate ligaments cannot be definitely excluded except by arthroscopy. As well as fractures of the carpometacarpal joints, fractures involving the ring structure of the carpus or ligament ruptures between carpal bones are frequently observed, and these lead to significantly impaired biomechanics. The prognosis is poor. The discontinuity of the ring must be repaired by means of osteosynthesis and/or suturing ligaments, with the carpal bones held in place by temporary arthrodesis using K-wires. Dislocation in this region requires rapid realignment, as untreated perilunate dislocation or dislocation of the lunate bone will lead to serious secondary damage, which can only be treated by salvage operations involving loss of function. Inappropriate treatment of an injury to the heel of the hand can lead to carpal collapse.     

Is atrial fibrillation an inflammatory disorder?

I read with great interest the excellent review on the influenceof inflammation in the pathogenesis of atrial fibrillation (AF)by Boos      

Thoraxtrauma

Chest injuries can be sustained in isolation or in association with multiple injuries. Life-threatening complications may ensue because organs that are vital to survival of the organism are situated within the thoracic cavity. These complications include airway obstruction, tension pneumothorax, wide open pneumothorax, flail chest, cardiac tamponade and massive hemothorax. The mortality of patients hospitalized with chest injury can be as high as 10%. Clinical examination and awareness of the possibility of other injuries (high level of suspicion) are essential, and standard chest X-ray, ultrasound and thoracic computed tomography may also be needed for the diagnosis. The first part of this serial paper on the management of chest injuries focuses on anatomical aspects, pathophysiology and symptoms, but mainly on the indications for the standard diagnostic procedures and further high-tech examinations.     

The European Menopause Survey 2005: women's perceptions on the menopause and postmenopausal hormone therapy.

OBJECTIVES: To identify and describe current women's thoughts about the menopause, hormone treatment (HT) and perceptions about breast cancer. METHODS: Between December 2004 and January 2005, 4201 postmenopausal women in seven European countries were interviewed via a standardized computer-aided telephone interview protocol. RESULTS: Almost all women reported to have experienced climacteric symptoms, and 63% of the women rated them as being severe. Only 52% of women were aware of the benefits of HT for relief of climacteric symptoms. Although 84% felt that severe symptoms should be treated, only 40% had used HT at some point in time. Thirty-four percent of the women preferring treatment with natural products did so because of the risk of breast cancer associated with HT. HT was recognized by 59% of the women as one of the most important contributors to an increased breast cancer risk. Most women received their information about HT and breast cancer risk from the media. CONCLUSIONS: This European survey reveals that the majority of women experience climacteric symptoms but that their decision whether or not to use HT is highly dependent on their concern about breast cancer risk. An increase in knowledge of the benefits and risks of HT is required for women to make appropriate decisions about hormone use.