Interval exercise versus continuous exercise in patients with moderate to severe chronic obstructive pulmonary disease – study protocol for a randomised controlled trial [ISRCTN11611768]

Background

We tested the hypothesis that ventilatory drive in hypoxia and hypercapnia is inversely correlated with the number of hypopneas and obstructive apneas per hour of sleep (obstructive apnea hypopnea index, OAHI) in children.

Methods

Fifty children, 6 to 12 years of age were studied. Participants had an in-home unattended polysomnogram to compute the OAHI. We subsequently estimated ventilatory drive in normoxia, at two levels of isocapnic hypoxia, and at three levels of hyperoxic hypercapnia in each subject. Experiments were done during wakefulness, and the mouth occlusion pressure measured 0.1 seconds after inspiratory onset (P_0.1) was measured in all conditions. The slope of the relation between P_0.1 and the partial pressure of end-tidal O₂ or CO₂ (P_ETO₂ and P_ETCO₂) served as the index of hypoxic or hypercapnic ventilatory drive.

Results

Hypoxic ventilatory drive correlated inversely with OAHI (r = -0.31, P = 0.041), but the hypercapnic ventilatory drive did not (r = -0.19, P = 0.27). We also found that the resting P_ETCO₂ was significantly and positively correlated with the OAHI, suggesting that high OAHI values were associated with resting CO₂ retention.

Conclusions

In awake children the OAHI correlates inversely with the hypoxic ventilatory drive and positively with the resting P_ETCO₂. Whether or not diminished hypoxic drive or resting CO₂ retention while awake can explain the severity of sleep-disordered breathing in this population is uncertain, but a reduced hypoxic ventilatory drive and resting CO₂ retention are associated with sleep-disordered breathing in 6–12 year old children.     

Injury and short term mortality of benthic stream fishes – a comparison of collection techniques

Small benthic fish such as darters are frequently collected for stream inventory purposes or to document habitat use, with the intent of releasing the fish unharmed following enumeration. The purpose of this study was to examine the injury and short term mortality (8 d) of greenside darters captured by live wire pot trapping and electrofishing, using two different settings (80Hz, 6ms and 60Hz, 6ms). Two different electrofishing techniques were used, spot electrofishing and sweep electrofishing. Short term mortality was highest for fish collected in live pot traps. Abrasion from the wire traps appeared to remove scales and irritate the skin. By the conclusion of the study, 74% of the fish caught in live pot traps were dead from fungal lesions. Greenside darters captured by all electrofishing methods exhibited low short term mortality (< 10%). The only initial mortality, hemorrhaging and spinal damage, occurred for fish collected using 80Hz, 6ms sweep technique, although the short term mortality was still far less than that observed among trapped fish. The spot electrofishing technique resulted in no injury, with either of the settings. Live trapping produces little initial mortality, and thus may be wrongly viewed as a safe alternative for the collection of threatened benthic stream fishes, compared to electrofishing. We suggest that researchers studying small fish in warmwater systems use caution when collecting and handling fish for subsequent release. This revised version was published online in July 2006 with corrections to the Cover Date.     

The effects of a low therapeutic dose of βCG fragment-lytic peptide conjugates on ovarian function and gonadotropin secretion in ewes: a randomized controlled trial

The main objective of this experiment was to determine and compare the effects of two lytic peptide conjugates, Phor21-?CG(ala) and ?CG(ala)-Phor21, at a low therapeutic dose (0.2 mg/kg body weight i.v.), on periovulatory ovarian and endocrine activity, and ensuing luteal function in an ovine experimental model. We hypothesized that the dense expression of LH/hCG receptors on the preovulatory follicle would present an appropriate target for the drugs and disrupt normal ovarian dynamics in sheep. Serum levels of reproductive hormones and ultrasonographic images were used for the assessment of periovulatory events following drug administration in 14 Rideau Arcott ewes; seven animals served as controls. Ovulations were synchronized with intravaginal progestogen-releasing sponges (medroxyprogesterone acetate, 60 mg) that were left in place for 12 days and a single i.m. injection of 750 IU of equine chorionic gonadotropin (eCG) given at sponge withdrawal. Both drugs were administered by i.v. injection 36 h post sponge removal/eCG injection, during the period of increasing LH responsiveness of potential ovulatory follicles and around the expected onset of the preovulatory surge of gonadotropins. No difference (p>0.05) was detected in the number of luteal structures per ewe in control versus treated animals during early luteogenesis. After drug administration, peak FSH concentrations were higher (p<0.05) in Phor21-?CG(ala)-treated compared to control ewes and circulating estradiol concentrations were lower (p<0.05) in ?CG(ala)-Phor21-treated animals. Mean serum progesterone concentrations were lower (p<0.05) in ?CG(ala)-Phor21-treated than control ewes during the luteal phase post-treatment. There were no differences (p>0.05) in the percentage of ewes that lambed or lamb characteristics between the three groups at lambing 9 months post-treatment. In summary, neither Phor21-?CG(ala) nor ?CG(ala)-Phor21 demonstrated adverse effects on the ovulatory process but the treatment with ?CG(ala)-Phor21 significantly depressed follicular and luteal steroidogenesis. With a lack of evidence for disruptive effects on endocrine function and fertility, these obsevations support the use of Phor21-?GG(ala) as a cancer pharmaceutical.     

Are the effects of a non-drug multimodal activation therapy of dementia sustainable? Follow-up study 10 months after completion of a randomised controlled trial

Background

Little is known about the long-term success of non-drug therapies for treating dementia, especially whether the effects are sustained after therapy ends. Here, we examined the effects of a one-year multimodal therapy 10 months after patients completed the therapy.

Methods

This randomised, controlled, single-blind, longitudinal trial involved 61 patients (catamnesis: n?=?52) with primary degenerative dementia in five nursing homes in Bavaria, Germany. The highly standardised intervention, MAKS, consisted of motor stimulation, practice of activities of daily living (ADLs), and cognitive stimulation. Each group of 10 patients was treated for 2 h, 6 days a week for 12 months. Control patients received standard nursing home care. At baseline, at the end of therapy (month 12), and 10 months thereafter (month 22), cognitive functioning was assessed using the cognitive subscale of the Alzheimer’s Disease Assessment Scale, and the ability to perform ADLs was assessed using the Erlangen Test of Activities of Daily Living.

Results

During the therapy phase, the MAKS patients maintained their cognitive function and ability to carry out ADLs. After the end of therapy, both the control and the MAKS groups deteriorated in both their cognitive function (control, p?=?0.02; MAKS, p?<?0.001) and their ability to carry out ADLs (control, p?<?0.001; MAKS, p?=?0.001). However, in a confound-adjusted multiple regression model, the ability of the MAKS group to perform ADLs remained significantly higher than that of the control group even 10 months after the end of therapy (H₀: β_MAKS?+?β_{MAKS month 22}?=?0; χ²?=?3.8568, p?=?0.0496). Cohen’s d for the difference between the two groups in ADLs and cognitive abilities 10 months after the end of therapy was 0.40 and 0.22, respectively.

Conclusions

A multimodal non-drug therapy of dementia resulted in stabilisation of the ability to perform ADLs, even beyond the end of therapy. To prevent functional decline for as long as possible, therapy should be performed continuously until the benefit for the patient ends. Follow-up studies on larger numbers of patients are needed to definitively confirm these results.

Trial registration

http://www.isrctn.com Identifier: ISRCTN87391496

     

Pro-oxidant effect of α-tocopherol in patients with Type 2 Diabetes after an oral glucose tolerance test – a randomised controlled trial

Background

Little information is available on leptin concentrations in individuals with IGT. This study aims to determine and correlate leptin levels to anthropometric measures of obesity in pre-diabetic, (IFG and IGT), type 2 diabetic and normoglycaemic Saudis.

Methods

308 adult Saudis (healthy controls n = 80; pre-diabetes n = 86; Type 2 diabetes n = 142) participated. Anthropometric parameters were measured and fasting blood samples taken. Serum insulin was analysed, using a solid phase enzyme amplified sensitivity immunoassay and also leptin concentrations, using radio-immunoassay. The remaining blood parameters were determined using standard laboratory procedures.

Results

Leptin levels of diabetic and pre-diabetic men were higher than in normoglycaemic men (12.4 [3.2–72] vs 3.9 [0.8–20.0] ng/mL, (median [interquartile range], p = 0.0001). In females, leptin levels were significantly higher in pre-diabetic subjects (14.09 [2.8–44.4] ng/mL) than in normoglycaemic subjects (10.2 [0.25–34.8] ng/mL) (p = 0.046). After adjustment for BMI and gender, hip circumference was associated with log leptin (p = 0.006 with R2 = 0.086) among all subjects.

Conclusion

Leptin is associated with measures of adiposity, hip circumference in particular, in the non-diabetic state among Saudi subjects. The higher leptin level among diabetics and pre-diabetics is not related to differences in anthropometric measures of obesity.     

DNA polymerase ι: The long and the short of it!

The cDNA encoding human DNA polymerase ι (POLI) was cloned in 1999. At that time, it was believed that the POLI gene encoded a protein of 715 amino acids. Advances in DNA sequencing technologies led to the realization that there is an upstream, in-frame initiation codon that would encode a DNA polymerase ι (polι) protein of 740 amino acids. The extra 25 amino acid region is rich in acidic residues (11/25) and is reasonably conserved in eukaryotes ranging from fish to humans. As a consequence, the curated Reference Sequence (RefSeq) database identified polι as a 740 amino acid protein. However, the existence of the 740 amino acid polι has never been shown experimentally. Using highly specific antibodies to the 25 N-terminal amino acids of polι, we were unable to detect the longer 740 amino acid (ι-long) isoform in western blots. However, trace amounts of the ι-long isoform were detected after enrichment by immunoprecipitation. One might argue that the longer isoform may have a distinct biological function, if it exhibits significant differences in its enzymatic properties from the shorter, well-characterized 715 amino acid polι. We therefore purified and characterized recombinant full-length (740 amino acid) polι-long and compared it to full-length (715 amino acid) polι-short in vitro. The metal ion requirements for optimal catalytic activity differ slightly between ι-long and ι-short, but under optimal conditions, both isoforms exhibit indistinguishable enzymatic properties in vitro. We also report that like ι-short, the ι-long isoform can be monoubiquitinated and polyubiuquitinated in vivo, as well as form damage induced foci in vivo. We conclude that the predominant isoform of DNA polι in human cells is the shorter 715 amino acid protein and that if, or when, expressed, the longer 740 amino acid isoform has identical properties to the considerably more abundant shorter isoform.     

Resistance exercise improves muscle strength,health status and pain intensity in fibromyalgia—a randomized controlled trial

IntroductionFibromyalgia (FM) is characterized by persistent widespread pain, increased pain sensitivity and tenderness. Muscle strength in women with FM is reduced compared to healthy women. The aim of this study was to examine the effects of a progressive resistance exercise program on muscle strength, health status, and current pain intensity in women with FM.MethodsA total of 130 women with FM (age 22–64 years, symptom duration 0–35 years) were included in this assessor-blinded randomized controlled multi-center trial examining the effects of progressive resistance group exercise compared with an active control group. A person-centred model of exercise was used to support the participants’ self-confidence for management of exercise because of known risks of activity-induced pain in FM. The intervention was performed twice a week for 15 weeks and was supervised by experienced physiotherapists. Primary outcome measure was isometric knee-extension force (Steve Strong®), secondary outcome measures were health status (FIQ total score), current pain intensity (VAS), 6MWT, isometric elbow-flexion force, hand-grip force, health related quality of life, pain disability, pain acceptance, fear avoidance beliefs, and patient global impression of change (PGIC). Outcomes were assessed at baseline and immediately after the intervention. Long-term follow up comprised the self-reported questionnaires only and was conducted after 13–18 months. Between-group and within-group differences were calculated using non-parametric statistics.ResultsSignificant improvements were found for isometric knee-extension force (p = 0.010), health status (p = 0.038), current pain intensity (p = 0.033), 6MWT (p = 0.003), isometric elbow flexion force (p = 0.02), pain disability (p = 0.005), and pain acceptance (p = 0.043) in the resistance exercise group (n = 56) when compared to the control group (n = 49). PGIC differed significantly (p = 0.001) in favor of the resistance exercise group at post-treatment examinations. No significant differences between the resistance exercise group and the active control group were found regarding change in self-reported questionnaires from baseline to 13–18 months.ConclusionsPerson-centered progressive resistance exercise was found to be a feasible mode of exercise for women with FM, improving muscle strength, health status, and current pain intensity when assessed immediately after the intervention.

Trial registration

ClinicalTrials.gov identification number: {"type":"clinical-trial","attrs":{"text":"NCT01226784","term_id":"NCT01226784"}}NCT01226784, Oct 21, 2010.     

Feasibility of a checklist in treating hypertension in primary care – base line results from a cluster-randomised controlled trial (check and support)

Background

Most patients with antihypertensive medication do not achieve their blood pressure (BP) target. The most important factor behind this failure is poor medication adherence. However, non-adherence to therapy does not concern only patients. Clinicians also tend to lack adherence to hypertension guidelines, overestimate BP control and be satisfied with inadequate BP control. The aim of this non-blinded, cluster-randomised, controlled study was to investigate if using a checklist would improve the quality of care in the initiation of new antihypertensive medication and help reduce non-adherence.

Methods

The study was conducted in eight primary care study centres in Central Finland, randomised to function as either intervention (n?=?4) or control sites (n?=?4). We included patients aged 30–75?years who were prescribed antihypertensive medication for the first time. Initiation of medication in the intervention group was carried out with a 9-item checklist, filled in together by the treating physician and the patient. Hypertension treatment in the control group was managed by the treating physician without a study-specific protocol.

Results

In total, 119 patients were included in the study, of which 118 were included in the analysis (n?=?59 in the control group, n?=?59 in the intervention group). When initiating antihypertensive medication, an adequate BP target was set for 19% of the patients in the control group and for 68% in the intervention group. Shortly after the appointment, only 14% of the patients in the control group were able to remember the adequate BP target, compared with 32% in the intervention group. The use of the checklist was also related to more regular agreement on the next follow-up appointment (64% in the control group versus 95% in the intervention group). No adverse events or side effects were related to the intervention.

Conclusions

Even highly motivated new hypertensive patients in Finnish primary care have significant gaps in their informational and behavioural skills. The use of a checklist for initiation of antihypertensive medication was related to significant improvement in these skills. Based on our findings, the use of a checklist might be a practical tool for addressing this problem.

Trial registration

NCT02377960. Date of registration: February 26th, 2015.

     

Morning bright light exposure has no influence on self-chosen exercise intensity and mood in overweight individuals – A randomized controlled trial

Overweight is a worldwide increasing public health issue. Physical exercise is a useful countermeasure. Overweight individuals choose rather low exercise intensities, but especially high exercise intensities lead to higher energy expenditure and show beneficial health effects compared to lower exercise intensities. However, especially in the morning higher exercise intensities are likely to be avoided due to higher subjective effort. Bright light exposure has shown to increase maximum performance. The aim of this study was to investigate if bright light exposure can also increase self-chosen exercise intensity. We hypothesized that morning bright light exposure increases self-chosen exercise intensity of subsequent exercise through increased mood and reduced sleepiness in overweight individuals. In this randomized controlled single-blind parallel group design, 26 overweight individuals (11 males, 15 females; age 25 ± 5.7 years; body mass index 28.9 ± 2.1 kg/m²) underwent three measurement appointments. On the first appointment, subjects performed a cardiopulmonary exercise test to measure maximum oxygen uptake (VO2max). Two days later a 30-min exercise session with self-chosen exercise intensity was performed for familiarization. Then subjects were randomly allocated to bright light (~4400 lx) or a control light (~230 lx) condition. Three to seven days later, subjects were exposed to light for 30 min starting at 8:00 am, immediately followed by a 30-min exercise session with persisting light exposure. Multidimensional mood questionnaires were filled out before and after the light exposure and after the exercise session. The primary outcome was the mean power output during the exercise session and the secondary outcome the rating on the three domains (i.e. good-bad; awake-tired; calm-nervous) of the multidimensional mood questionnaire. Mean power output during the exercise session was 92 ± 19 W in bright light and 80 ± 37 W in control light, respectively. In the multivariate analysis adjusted for VO2max, the mean power output during the exercise session was 8.5 W higher (95% confidence interval ?12.7, 29.7; p = 0.416) for participants in bright light compared to control light. There were no significant differences between the groups for any of the three domains of the questionnaire at any time point. This is in contrast to longer lasting intervention studies that show positive influences on mood and suggests that bright light therapy requires repetitive sessions to improve mood in overweight individuals. In conclusion bright light exposure does not acutely increase self-chosen exercise intensity or improve mood in a 30-min exercise session starting at 08:30. However, regarding the fact that overweight is a worldwide and rapidly increasing public health issue even small increases in exercise intensity may be relevant. The trend toward superiority of bright light over control light implicates that further studies may be conducted in a larger scale.

Abbreviations: VO2max: maximum oxygen uptake; 95% CI: 95% confidence interval; SD: standard deviation     

Effects of short term pollution on the level of fluctuating asymmetry – a case study using damselflies

Fluctuating asymmetry (FA), a measure of developmental stability, has been suggested as a monitoring tool for environmental pollution. However, there have been few investigations into the effects of short term pollution on the level of FA. This paper explores effects of exposing late instar larvae to short term pollution on the level of FA in the wings of adult damselflies. In these insects FA in wing length and in cell patterns have different windows of opportunity in relation to environmental stress. If increased environmental stress is applied after the window of opportunity of one trait had closed, while the window of the other trait was still open then the level of FA of the first trait should not be altered whereas that of the latter should increase. If short term pollution killed part of a population, symmetrical individuals (low FA) should survive better than highly asymmetrical ones, because FA reflects the overall ability of an individual to cope with stress. If the pollution event occurred at a time when the level of FA was already fixed, the level of FA of the remaining population should be lower than that in controls. An experiment was carried out, using 10 artificial ponds, each holding a population of larvae of the damselfly Xanthocnemis zealandica (McLachlan). Damselfly larvae were exposed to carbaryl at a nominal concentration of 100 g l^–1, which reduced emergence success after 10–20 days by ca. 50%. Based on laboratory experiments, it was assumed that despite the high mortality, the short exposure to carbaryl late in the last instar would ensure that the wing cell patterns of the damselflies were not altered by the increased stress. The level of FA in wing length increased in the damselflies surviving the exposure to carbaryl but the level of FA in cell patterns did not differ significantly between the treatment and the control. The effects of differential mortality, as well as the effects of pollution, on the level of FA in traits with different windows of opportunity need further investigation.     

Leptin attenuates the detrimental effects of β-amyloid on spatial memory and hippocampal later-phase long term potentiation in rats

β-Amyloid (Aβ) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Aβ in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16 kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Aβ-induced deficits in spatial memory and in vivo hippocampal late-phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1 μg) effectively alleviated Aβ1–42 (20 μg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Aβ1–42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Aβ-induced deficits in learning and memory and the maintenance of L-LTP.     

Does suppressing luteinising hormone secretion reduce the miscarriage rate? Results of a randomised controlled trial.

OBJECTIVE--To determine whether prepregnancy pituitary suppression of luteinising hormone secretion with a luteinising hormone releasing hormone analogue improves the outcome of pregnancy in ovulatory women with a history of recurrent miscarriage, polycystic ovaries, and hypersecretion of luteinising hormone. DESIGN--Randomised controlled trial. SETTING--Specialist recurrent miscarriage clinic. SUBJECTS--106 women with a history of three or more consecutive first trimester miscarriages, polycystic ovaries, and hypersecretion of luteinising hormone. INTERVENTIONS--Women were randomised before conception to receive pituitary suppression with a luteinising hormone releasing hormone analogue followed by low dose ovulation induction and luteal phase progesterone (group 1) or were allowed to ovulate spontaneously and then given luteal phase progesterone alone or luteal phase placebo alone (group 2). No drugs were prescribed in pregnancy. MAIN OUTCOME MEASURES--Conception and live birth rates over six cycles. RESULTS--Conception rates in the pituitary suppression and luteal phase support groups were 80% (40/50 women) and 82% (46/56) respectively (NS). Live birth rates were 65% (26/40) and 76% (35/46) respectively (NS). In the luteal phase support group there was no difference in the outcome of pregnancy between women given progesterone and those given placebo pessaries. Live birth rates from an intention to treat analysis were 52% (26/50 pregnancies) in the group given pituitary suppression and 63% (35/56) in the controls (NS). CONCLUSIONS--Prepregnancy suppression of high luteinising hormone concentrations in ovulatory women with recurrent miscarriage and hypersecretion of luteinising hormone does not improve the outcome of pregnancy. The outcome of pregnancy without pituitary suppression is excellent.     

The short—term variation of asthma in Brisbane: Its relation to the weather and other factors

In the cooler portions of the six years 1961–1966, there were 22 weeks in which the night attendances for asthma at the Royal Brisbane Hospital Casualty Department were much higher than would be expected from the seasonal and annual variation, 23 weeks in which they were much lower, and 114 intermediate weeks. The high-asthma weeks differed significantly from intermediate weeks in having on the average a greater decrease from the previous week in mean and minimum temperature, dew point, relative humidity and rainfall, and a greater increase in hours of sunshine. There was a significant association with the arrival of a cold dry change. No significant difference was found with smoke density, fungal elements or pollens. In many of the individual high-asthma weeks the increase in asthma occurred within 48 hours after a definite fall in minimum temperature or dew point or both. However, in some of the weeks, particularly in spring, there had not been a cold or dry change, and many cold dry changes were not followed by an increase in asthma. The low-asthma weeks differed significantly from intermediate weeks in having on the average a higher dew point and relative humidity, more rainy days, a lower temperature range and fewer hours of sunshine. This applied particularly to autumn. In autumn and spring, rain was significantly less frequent on days with asthma attendances than on days with none. These relationships are largely the converse of those with high-asthma weeks.

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Zusammenfassung Während der kühleren Jahreszeiten in 6 Jahren (1961–1966) waren 22 Wochen in denen die Anzahl der nächtlichen Einlieferungen wegen Asthma im Royal Brisbane Hospital weit höher war als die erwartete Anzahl, 23 Wochen in denen sie wesentlich geringer war, und 114 Wochen mit einer mittleren Anzahl Fälle. Die Wetterbedingungen während der Wochen mit vielen Asthmafällen waren signifikant unterschieden von denen mit mittlerer Häufigkeit. Im Mittel waren die mittlere und die Minimaltemperatur tiefer als in der vorausgegangenen Woche, es waren weniger Regen, niedrigere Luftfeuchtigkeit und mehr Stunden Sonnenschein. Es bestand eine signifikante Beziehung zu dem Eintreffen kalter trockener Luft. Dagegen bestand keine Beziehung zur Dichte der Luftverunreinigung und der Menge Pilzsporen und Pollen in der Luft. In vielen Wochen trat Asthma innerhalb 48 Stunden nach dem Fall der Temperatur und Feuchtigkeit auf. Während einiger Wochen dagegen, besonders im Frühling, lag dieser Wetterwechsel nicht vor und in vielen Fällen bewirkte der Wechsel keinen Anstieg der Asthmahäufigkeit. Während der Wochen mit niedriger Asthmahäufigkeit waren im Mittel die Feuchtigkeit erhöht, ein geringerer Temperaturwechsel, weniger Regen und weniger Sonnenscheinstunden, besonders im Herbst. Im Herbst und Frühling war signifikant weniger Regen an Tagen mit als an Tagen ohne Asthmameldungen. Diese Beziehungen waren weitgehend umgekehrt von denen in Wochen mit hoher Asthmahäufigkeit.

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Resume Des statistiques de la permanence du "Royal Brisbane Hospital" il appert que durant les périodes froides des années 1961 à 1966, on a dénombré 22 semaines pendant lesquelles, la nuit, les entrées d'urgence causées par des crises d'asthme furent beaucoup plus nombreuses que ne le laissaient supposer les variations saisonnières et annuelles. Durant les mêmes laps de temps, on en a décompté 23 pendant lesquelles les crises nocturnes d'asthme étaient moins fréquentes et 114 qui occupent une position intermédiaire. Les semaines à haute fréquence d'asthme présentent des moyennes de température, des minimums journaliers, des points de rosée, des humidités relatives et des précipitations inférieurs et une durée d'insolation supérieure à la normale et cela de façon significative. On a pu déceler une relation significative entre les crises d'asthme et des invasions d'air froid et sec. On n'a par contre pas pu déceler de différences en ce qui concerne le taux de fumée ou le nombre de spores et de grains de pollen. Dans bon nombre de semaines avec de hautes fréquences d'asthme, le déclenchement des crises se produit 48 heures après la chute du minimum de la température ou du point de rosee, voire des 2 ensemble. Pourtant, quelques unes de ces semaines — au printemps surtout — n'ont pas connu d'invasion d'air froid et sec et de nombreuses invasions de ce type ne furent pas suivies d'une augmentation du nombre de crises. Les semaines de faible fréquence se distinguent de façon significative de la classe intermédiaire en ce sens qu'elles présentent en moyenne des points de rosée et une humidité plus élevés, plus de jours avec précipitations, une température plus basse et moins d'heures d'insolation. Ceci est valable surtout en automne. En automne et au printemps, la pluie fut moins fréquente les jours où l'on note des crises d'asthme qu'à ceux où il n'y en a pas. Cette relation est en général inverse à celle que l'on rencontre durant les semaines à haute fréquence de crises d'asthme.

     

The antifibrotic effects of TGF-β1 siRNA on hepatic fibrosis in rats

Background/aims: Hepatic fibrosis results from the excessive secretion of matrix proteins by hepatic stellate cells (HSCs), which proliferate during fibrotic liver injury. Transforming growth factor (TGF)-β1 is the dominant stimulus for extracellular matrix (ECM) production by stellate cells. Our study was designed to investigate the antifibrotic effects of using short interference RNA (siRNA) to target TGF-β1 in hepatic fibrosis and its mechanism in rats exposed to a high-fat diet and carbon tetrachloride (CCL4). Methods: A total of 40 healthy, male SD (Sprague–Dawley) rats were randomly divided into five even groups containing of eight rats each: normal group, model group, TGF-β1 siRNA 0.125 mg/kg treatment group, TGF-β1 siRNA 0.25 mg/kg treatment group and TGF-β1 siRNA negative control group (0.25 mg/kg). CCL4 and a high-fat diet were used for 8 weeks to induce hepatic fibrosis. All the rats were then sacrificed to collect liver tissue samples. A portion of the liver samples were soaked in formalin for Hematoxylin–Eosin staining, classifying the degree of liver fibrosis, and detecting the expression of type I and III collagen and TGF-β1; the remaining liver samples were stored in liquid nitrogen to be used for detecting TGF-β1 by Western blotting and for measuring the mRNA expression of type I and III collagen and TGF-β1 by quantitative real-time polymerase chain reaction. Results: Comparing the TGF-β1 siRNA 0.25 mg/kg treatment group to the model group, the TGF-β1 siRNA negative control group and the TGF-β1 siRNA 0.125 mg/kg treatment group showed significantly reduced levels of pathological changes, protein expression and the mRNA expression of TGF-β1, type I collagen and type III collagen (P < 0.01). Conclusions: Using siRNA to target TGF-β1 can inhibit the expression of TGF-β1 and attenuate rat hepatic fibrosis induced by a high-fat diet and CCL4. A possible mechanism is through the down-regulation of TGF-β1 expression, which could inhibit HSC activation, as well as the proliferation and collagen production of collagen reducing, so that collagen deposition in the liver is reduced.