A decrease in soleus muscle force generation in rats after downhill running.

The purpose of the present study was to investigate the immediate and 48-hr post-exercise effects of eccentric contraction-biased exercise on the contractile properties of the soleus muscle in situ. Adult male Wistar rats were categorised into sedentary control rats (n = 10), rats studied immediately (n = 10), and rats studied 48 hours after the exercise (n = 10). The exercise protocol consisted of a 90-min intermittent downhill running (-16 degrees, 16 m/min) on a motor-driven treadmill. The contractile properties of the soleus muscle were recorded following i.p. chloral hydrate anaesthesia. Isometric twitch force (Pt), time-to-peak tension (TPT), half-relaxation time (1/2 RT), and tetanic force at stimulation frequencies of 40, 80, and 100 Hz were recorded. A low-frequency muscle fatigue protocol (stimulation at 4 Hz for 5 min) was applied to test for fatigability. The main findings indicated that Pt generation dropped both immediately and 48 hr after the exercise, while tetanic force was partially restored after 48 hr. Exercise-induced E-C coupling failure and contractile machinery disorganisation due to muscle injury are put forward as the main force reduction causes.     

Ca2+/calcineurin regulation of cloned vascular KATP channels: crosstalk with the protein kinase A pathway

Background and purpose:

Vascular ATP-sensitive potassium (K_ATP) channels are activated by cyclic AMP elevating vasodilators through protein kinase A (PKA). Direct channel phosphorylation is a critical mechanism, though the phosphatase opposing these effects is unknown. Previously, we reported that calcineurin, a Ca²⁺-dependent phosphatase, inhibits K_ATP channels, though neither the site nor the calcineurin isoform involved is established. Given that the type-2 regulatory (RII) subunit of PKA is a substrate for calcineurin we considered whether calcineurin regulates channel activity through interacting with PKA.

Experimental approach:

Whole-cell recordings were made in HEK-293 cells stably expressing the vascular K_ATP channel (K_IR6.1/SUR2B). The effect of intracellular Ca²⁺ and modulators of the calcineurin and PKA pathway on glibenclamide-sensitive currents were examined.

Key results:

Constitutively active calcineurin Aα but not Aβ significantly attenuated K_ATP currents activated by low intracellular Ca²⁺, whereas calcineurin inhibitors had the opposite effect. PKA inhibitors reduced basal K_ATP currents and responses to calcineurin inhibitors, consistent with the notion that some calcineurin action involves inhibition of PKA. However, raising intracellular Ca²⁺ (equivalent to increasing calcineurin activity), almost completely inhibited K_ATP channel activation induced by the catalytic subunit of PKA, whose enzymatic activity is independent of the RII subunit. In vitro phosphorylation experiments showed calcineurin could directly dephosphorylate a site in Kir6.1 that was previously phosphorylated by PKA.

Conclusions and implications:

Calcineurin Aα regulates K_IR6.1/SUR2B by inhibiting PKA-dependent phosphorylation of the channel as well as PKA itself. Such a mechanism is likely to directly oppose the action of vasodilators on the K_ATP channel.British Journal of Pharmacology (2009) 157, 554–564; doi:10.1111/j.1476-5381.2009.00221.x; published online 7 May 2009This article is commented on by Tammaro, pp. 551–553 of this issue and is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Effect of aerobic training on 99mTc-methoxy isobutyl isonitrile (99mTc-sestamibi) uptake by myocardium and skeletal muscle: implication for noninvasive assessment of muscle metabolic profile

Aim: The effect of long‐term endurance training on skeletal muscle and myocardial uptake of ^99mTc‐sestamibi, a radiopharmaceutical accumulating in the mitochondria, was investigated. Methods: Twenty‐six Wistar rats were divided into a trained (5 days week^?1 endurance running for 14 weeks) and an untrained group. On completion of training, ^99mTc‐sestamibi was administered and, 2 h post‐injection, the myocardium and the soleus, extensor digitorum longus (EDL) and medial gastrocnemius (MG) muscles were removed for the measurement of cytochrome c oxidase (CCO) activity and ^99mTc‐sestamibi uptake. Tissue ^99mTc‐sestamibi kinetics was preliminarily studied in 16 other rats for up to 2 h post‐injection. Results: Two hours post‐injection ^99mTc‐sestamibi uptake was either stable (myocardium) or still rising (skeletal muscles). Both CCO activity and ^99mTc‐sestamibi uptake decreased in the same order (myocardium, soleus, EDL, MG) in the tissues examined. The CCO activity of the EDL and MG muscles was higher (P < 0.05) in the trained compared to the untrained group. ^99mTc‐sestamibi uptake in the soleus and EDL muscles was higher (P < 0.05) in the trained compared to the untrained rats, whereas the difference in MG was marginally significant (P = 0.06) in favour of the trained group. Conclusions: Long‐term endurance training, resulting in elevated skeletal muscle CCO activity, is also associated with a similar increase in ^99mTc‐sestamibi uptake. This finding suggests that ^99mTc‐sestamibi could be used in imaging assessment of skeletal muscle metabolism with possible applications in both clinical and sports medicine settings.     

Adnexal and cul-de-sac abnormalities: transvaginal sonography

Sixty-seven patients selectively chosen from 354 undergoing conventional transabdominal (TA) sonography for evaluation of a clinically suspected adnexal mass subsequently underwent transvaginal (TV) sonography either because the TA sonograms were technically suboptimal or because it was not possible to characterize with certainty an abnormality identified with TA sonography. TV sonography added diagnostically useful information in 25 of 28 patients with cystic pathologic changes in the adnexa uteri. Eight of 12 patients with tuboovarian abscess and nonspecific adnexal masses visualized with TA sonography had tube-shaped fluid collections characteristic of pyosalpinx identified with TV sonography. TV sonography added diagnostically useful information in all seven patients with diseases of the cul-de-sac (rectouterine fossa) and allowed differentiation of adnexal from primary uterine disease in three patients with TA sonograms on which findings were equivocal. It also expedited the diagnosis of a tubal pregnancy in ten of 14 patients and was useful in the detection of adhesions and perforated intrauterine devices. These results indicate that adjunctive TV sonography can provide important diagnostic information.     

The Impact of Chronic Inflammation on Bone Turnover in Hemodialysis Patients

Background. Renal osteodystrophy is very common in hemodialysis (HD) patients. HD is a chronic inflammatory state. Studies in other pathological entities have shown an impact of chronic inflammation on bone metabolism. In the present study, the impact of chronic inflammation on bone turnover in HD patients was evaluated.?Patients and methods. Thirty-three anuric HD patients free of other pathological conditions or medications that affect immune system or bone metabolism and 30 healthy volunteers enrolled into the study. Intact parathyroid hormone (iPTH), the markers of inflammation IL-6 and CRP, as well as the markers of bone turnover osteocalcin (OCN) and beta-isomerized C-terminal cross-linked peptide of collagen type I (β-CTx) were measured in the serum.?Results. All evaluated factors were increased in HD patients. In the HD group, the serum marker of osteoblastic activity OCN was related inversely to patients' age (r?=??0.469, p?=?0.006), CRP (rho?=??0.460, p?=?0.007), and IL-6 (r?=??0.485, p?=?0.004) but positively to iPTH (r?=?0.707, p < 0.001). Similarly, the serum marker of osteoclastic activity β-CTx was related inversely to patients' age (r?=??0.383, p?=??0.028), CRP (rho?=?–0.466, p?=?0.006), and IL-6 (r?=??0.460, p?=?0.007) but positively to iPTH (r?=?0.657, p < 0.001). Multiple linear regression analysis revealed that IL-6 affects bone turnover independently of PTH and to the opposite direction.?Conclusion. Chronic inflammation has a negative impact on bone turnover in HD patients. Certainly, further research and large clinical trials are needed for definite conclusions and for clarifying the exact molecular mechanisms implicated in the interaction between the immune system and bone metabolism in HD patients.     

Post-pubescent to mature fathers: increase in progeny quality?

In the mouse, offspring born from mature fathers exhibit better behavioural performances (for spontaneous activity in both sex and learning capacity in males) than those born from post-pubescent fathers. These behavioural variations are not accompanied by other obvious modifications. They could correspond to what has been observed in man relating to the results in a psychometric test undergone by male progeny born from very young to mature fathers. These data and those which show a decrease in mental performance in rats and human males born from mature to senescent fathers suggest the participation of some genetic factors in these phenomena.      

间质干细胞与免疫调节

目的:间质干细胞能够逃避免疫识别,抑制免疫反应特征。文章就近年来间质干细胞及其免疫调节作用进行综述。资料来源:应用计算机检索PUBMED 1976-01/2006-01期间的相关文章,检索词为"mesenchymal stem cells,immune modulation",并限定文章语言种类为English。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:文章所述内容应与间质干细胞及其免疫调节作用相关。排除标准:重复研究或Meta分析类文章。资料提炼:共收集到263篇相关文献,68篇文献符合纳入标准,排除的195篇文献为内容陈旧或重复。符合纳入标准的68篇文献中,分别涉及间质干细胞的免疫原性、免疫抑制作用及机制、应用等内容。资料综合:间质干细胞广泛存在于各种组织中,本身具有免疫原性低的特点,可以逃避同种异基因免疫识别。间质干细胞在体外、体内均有明确的免疫抑制作用,与间质干细胞对树突状细胞、T细胞、自然杀伤细胞等的调控作用有关。间质干细胞尚可对转化生长因子、白细胞介素、基质细胞来源因子、NF-κB配体、前列腺素、吲哚胺2,3-二氧酶等可溶性因子产生影响。由于间质干细胞多方面的免疫调节活性,使其拥有良好的应用前景,目前已在移植物抗宿主病及自身免疫疾病的治疗中发挥了作用。结论:间质干细胞无论在体内或体外均对T细胞的活化有抑制作用,可调节在同种异体抗原的识别和清除过程中主要细胞群的免疫功能,包括抗原递呈细胞、T细胞和自然杀伤细胞,但其调节免疫抑制作用的分子机制尚未被完全阐明。     

Elemental diet: a therapeutic approach in chronic inflammatory bowel disease

The therapeutic effect of an elemental diet (Pepti 2000) and blended normal diet (placebo) was investigated in 43 out-patients with chronic inflammatory bowel disease (IBD); 24 with ulcerative colitis (UC) and 19 with Crohn's disease (CD), in a mild to moderate state of disease activity. A pilot study on healthy volunteers was executed to investigate palatability of the two diets. The patients were randomized in a double-blind study to the two diet regimes for 14 d. A simultaneous determination of laboratory data including plasma C3c split product and urinary excretion of 51Cr-EDTA was carried out together with a careful registration of the clinical symptoms and signs. No significant effect on the stage of clinical activity was seen in CD. A significant effect on clinical activity was obtained in both UC groups. The clinical improvement was primarily due to a decrease in number of bowel movements both in the elemental diet group and in the group of patients on the blended normal diet. The gross appearance of rectal mucosa did not improve during the study period in the Pepti 2000 or in the placebo group. The concentration of complement split products in plasma remained unchanged. 51Cr-EDTA excretion, as an expression of a leaky bowel mucosa, also remained unchanged. It was concluded that an effect on inflammation could not be demonstrated even if both diets seem to have a beneficial effect on the stage of clinical activity, especially diarrhoea, in patients with UC.     

EGF促进RPE细胞毒蕈碱受体诱导的磷酸肌醇形成：受体间交互作用分析

对培养人眼视网膜色素上皮（RPE）细胞磷酸肌醇（InsPs）水平的分析表明，Carbachol显著刺激RPE细胞InsPs水平的升高，且该效应可被阿托品所阻断，表明在人眼RPE细胞存在毒蕈碱受体。去甲肾上腺素、5-羟色胺、表皮生长因子（EGF）、异丙肾上腺素和NECA对InsPs基础水平无明显影响。异丙肾上腺素和NECA对Carbachol刺激InsPs的效应也无明显影响；但EGF显著促进Carbacol刺激人眼RPE细胞InsPs水平升高的效应。提示在人眼RPE细胞EGF与毒蕈碱受体之间存在有受体间交互作用。 （中华眼底病杂志，1994，10：220-222）