Effects of prolonged exposure to and physical training in hypobaric conditions on skeletal muscle morphology and metabolic enzymes in rats

Adaptations of skeletal muscle morphology and metabolic enzymes were studied after prolonged training in and exposure to hypobaric (740 –770 mbar) as well as normobaric conditions in rats performing treadmill running training for 10, 21 and 56 days. Animals sacrificed after 91 days served as recovery groups from training and hypobaric exposure for 56 days. The rats were divided into normobaric sedentary (NS) and training (NT) groups and hypobaric sedentary (HS) and training (HT) groups. The weights of extensor digitorum longus (EDL) and soleus (SOL) muscles increased significantly in the 56HS and the 56HT groups compared with the 56NS group, the increase being greatest in the 56HS group. No differences in the mean fibre areas (MFA) of these muscles could be seen, whereas clearly reduced MFAs of type IIA and IIB were observed in the tibialis anterior (TA) muscle. However, fibre area distribution analyses in the EDL and TA muscles showed a higher proportion of larger fibers in the 56HS and 56HT groups than in the respective normobaric groups. On the contrary, in SOL muscles the proportion of smaller fibers was higher in the hypobaric than in normobaric groups at 56 days. Increased activities of citrate synthase and β-hydroxyacyl-CoA-dehydrogenase in SOL and TA muscles in the 56HT group indicate an increase in oxidative capacity. It is concluded that exposure to, and training in moderate hypobaric conditions leads to a positive muscle protein balance which is reflected in increased muscle weights. However, the sites of increased protein synthesis and the possible hyperplasia remain to be studied further. Received : 27 April 1995/Received after revision: 25 October 1995/Accepted: 27 November 1995     

Increased Toll-like receptor 9 expression indicates adverse prognosis in oesophageal adenocarcinoma

Kauppila J H, Takala H, Selander K S, Lehenkari P P, Saarnio J & Karttunen T J
(2011) Histopathology 59 , 643–649 Increased Toll‐like receptor 9 expression indicates adverse prognosis in oesophageal adenocarcinoma Aims: Toll‐like receptor 9 (TLR‐9) is a cellular DNA receptor that has been linked previously to invasion in various cancers. The aim of this study was to investigate TLR‐9 expression and its possible association with prognosis in oesophageal adenocarcinoma. Methods and results: Immunohistochemical TLR‐9 expression was graded in clinical specimens (n = 76) of oesophageal adenocarcinoma. The TLR‐9 immunostaining intensity was compared with tumour grade, stage and indicators of proliferation, apoptosis and tumour vascular supply. High TLR‐9 expression correlated with advanced tumour stage, tumour unresectability, poor differentiation and high proliferation. Strong immunoreactivity of TLR‐9 also indicated poor overall survival. Conclusions: High TLR‐9 expression is associated with poor differentiation, a high proliferation rate and disseminated disease. Accordingly, increased TLR‐9 expression may contribute to the growth and metastatic properties of oesophageal adenocarcinoma.     

Increased mRNAs for procollagens and key regulating enzymes in rat skeletal muscle following downhill running

 The purpose of the study was to investigate pre-translational regulation of collagen expression after a single bout of exercise. We analysed steady-state messenger ribonucleic acid (mRNA) levels for collagen types I, III and IV, α- and β-subunits of prolyl 4-hydroxylase and lysyl oxidase (enzymes modifying procollagen chains), and enzyme activity of prolyl 4-hydroxylase from rat soleus muscle (MS) and the red parts of quadriceps femoris muscle (MQF) after 12 h and after 1, 2, 4, 7 and 14 days of downhill (–13.5°) treadmill running at a speed of 17 m·min^–1 for 130 min. Histological and biochemical assays revealed exercise-induced muscle damage in MQF but not MS. Steady-state mRNA levels for the α- and β-subunits of prolyl 4-hydroxylase in MQF, lysyl oxidase in MS and MQF were increased 12 h after running, whereas prolyl 4-hydroxylase activity did not increase until 2 days after exercise. The mRNA levels for the fibrillar collagens (I and III) and basement membrane type IV collagen significantly increased 1 day and 12 h after exertion, respectively. Peak mRNA levels were observed 2–4 days after running, the increases being more pronounced in MQF than in MS. No significant changes were observed in types I or III collagen at the protein level. Strenuous downhill running thus causes an increase in gene expression for collagen types I and III and their post-translational modifying enzymes in skeletal muscle in a co-ordinated manner. These changes, together with the increased gene expression of type IV collagen, may represent the regenerative response of muscle extracellular matrix to exercise-induced injury and an adaptive response to running exertion. Received: 20 July 1998 / Received after revision: 30 November 1998 / Accepted: 26 January 1999     

Detection of a soluble form of the complement membrane attack complex inhibitor CD59 in plasma after acute myocardial infarction

Activation of the complement system has been documented in both experimental and clinical studies of acute myocardial infarction (AMI). Our earlier immunohistochemical studies have shown that the deposition of the membrane attack complex (MAC) of complement is associated with the loss of protectin (CD59), a glycosyl-phosphatidylinositol (GPI)-anchored sarcolemmal regulator of MAC, from the human and rat infarcted myocardium. In this study we detected, using an enzyme immunoassay (EIA), CD59 in the plasma of AMI patients at a concentration of 23.0+/-8.4 ng/ml (mean +/- SD; n = 17) at 4 h and 27.3+/-11.8 ng/ml (n = 24) at 24 h after AMI. Both values were significantly higher than in healthy controls (7.8+/-6.4 ng/ml; n = 20; P<0.001). The amount of CD59 correlated with the level of soluble terminal complement complexes (SC5b-9; r = 0.84; P<0.01) in the plasmas of AMI patients. Our results suggest that myocardial damage leads to release of CD59 from the sarcolemmal cell membranes during AMI.     

Serum concentrations of collagen degrading enzymes and their inhibitors after downhill running

In the present study the release of proteins degrading extracellular matrix compounds to circulation was measured after damaging exercise in humans. Muscle damage was induced by downhill running; furthermore, the exercise was performed at both cold temperature (5 degrees C) and room temperature (22 degrees C) to study also the possible effect of environmental temperature on serum concentrations of matrix metalloproteinases MMP-2 and MMP-9, tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2, and MMP-2/TIMP-2 complex, and muscle damage monitored by serum creatine kinase measurements. Results were compared with those obtained from patients having rhabdomyolysis, myositis and Becker muscular dystrophy. The present study demonstrates an acute increase in serum concentrations of MMP-9, TIMP-1, and MMP-2/TIMP-2 complex, but no changes in serum MMP-2 concentrations in response to eccentric exercise. Serum creatine kinase activity data suggest greater muscle damage after downhill running in a cold environment than at room temperature. The present observations about at most slight changes in serum MMP and TIMP concentrations and lack of their correlation to increased serum creatine kinase after exercise indicate that serum measurements of MMPs and TIMPs do not sensitively respond to exercise induced skeletal muscle damage and extracellular matrix regeneration. On the other hand, severe skeletal muscle damage, such as rhabdomyolysis, myositis and Becker muscular dystrophy, seemed to have an effect on serum MMP and TIMP concentrations.     

Sampling rate causes bias in APACHE II and SAPS II scores

OBJECTIVE: To study the effect of sampling rate of laboratory and haemodynamic data on severity scorings and predicted risk of hospital death. DESIGN: Prospective study. SETTING: Medical-surgical intensive care unit (ICU) with 23 beds in a university hospital. PATIENTS: Sixty-nine consecutive emergency admission patients. INTERVENTIONS: Blood samples were drawn from indwelling arterial lines for the laboratory tests of all variables contained in the APACHE II and SAPS II scores at 2-hourly intervals from the time of admission up to 24 h or earlier discharge or death of the patient. Haemodynamic data and temperature were collected either manually by the attending nurse once an hour or as 2-min median values automatically using a Clinical Information Management System (CIMS, Clinisoft, Datex-Ohmeda, Helsinki, Finland). Three sets of severity scores were obtained. (1) "Traditional" scores (haemodynamic data from manual records and laboratory values from tests taken at admission and subsequently on clinical basis only). (2) "CIMS" scores (haemodynamic data from 2-min median values and laboratory values prescribed on clinical indication) and (3) "High rate" scores (haemodynamic data from 2-min median values and laboratory values at 2-hourly intervals). Probability of hospital death was calculated using the SAPS II and APACHE II scores, respectively. RESULTS: Increasing the sampling rate of haemodynamic monitoring interval to 2-min from once per hour resulted in 7.8 % and 11.5 % increases (p < 0.001) in the APACHE II and SAPS II scores, respectively. The combined effect of increased sampling rate of haemodynamic and laboratory tests on the APACHE II and SAPS II scores was 14.4 % and 14.5 % compared to traditional scores (p < 0.001), respectively. The probability of hospital death increased from 0.23 and 0.21 ("traditional" SAPS II and APACHE II) to 0.31 and 0.25 ("high rate" SAPS II and APACHE II), respectively, and, because eight patients died, standardised mortality ratio (SMR) decreased from 0.53 to 0.41 (SAPS II) and from 0.60 to 0.50 (APACHE II). CONCLUSIONS: Increased sampling rate results in higher scores and lower SMR. Comparisons between hospitals using severity scores are biased due to differences in the sampling rates.     

国产利培酮（索乐）治疗精神分裂症多中心开放性临床研究

目的：评价国产利培酮（索乐）治疗精神分裂症的疗效和安全性。方法：通过对全国45家精神病医院的962例精神分裂症患者进行多中心,大样本,开放性的为期8周的治疗观察。采用PANSS、CGI、SAS和TESS评定疗效和不良反应。结果：国产利培酮（索乐）对精神分裂症总有效率84.3%,临床总体疗效肯定,不良反应轻,主要是轻度的锥体外系反应,体重增加,因其程度轻,病人基本能耐受。结论：国产利培酮（索乐）对精神分裂症阳性症状及阴性症状均有效,起效快,安全性高,患者对该药依从性好,可作为精神分裂症的首选药物之一。     

Dysfibrinogenemia associated with thrombosis and third-trimester fetal loss. A case report

Dysfibrinogenemias are rare genetic disorders that are clinically silent, cause a mild bleeding tendency or have thromboembolic manifestations. During pregnancy they often cause hemorrhage and first-trimester abortions. A patient with a severe thrombotic tendency during pregnancy had a third-trimester fetal loss.     

Water, sodium and acid-base balance in premature infants: therapeutical aspects

One of the main targets of fluid therapy in premature infants is to avoid variations in osmolality, which mainly means providing a stable sodium, glucose, and acid-base balance. Water, sodium, and acid-base balance were measured in 20 infants appropriate-for-gestational age with a gestational age less than or equal to 34 weeks. The infants were randomly assigned to one of two treatment groups. Fluid intake was restricted and air humidity in the incubator was high in order to minimize insensible water loss. Sodium intake in Group 1 was 2 mmol/kg/day and consisted of sodium chloride. Sodium intake in Group 2 was 4 mmol/kg/day and consisted of both sodium chloride and acetate. Weight loss was appropriate in both groups. In the high sodium intake group there was a tendency towards a more stable plasma sodium concentration than in the low sodium intake group. The use of sodium acetate was efficient and practical as normal acid-base balance was maintained. The protocol with restricted fluid intake (1st day 50 ml/kg, 2nd day 70 ml/kg, 3rd day 90 ml/kg, and 4th day 110 ml/kg), high air humidity, a sodium supply of 3 to 4 mmol/kg/day, and a slow correction of metabolic acidosis with sodium acetate, yields suitable guidelines in planning fluid and electrolyte therapy in premature infants less than or equal to 34 weeks' gestation.