bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF QUANTITATIVE TRAIT LOCI FOR LIPID PHENOTYPES IN THE RAT ARE INFLUENCED BY AGE
Authors: Kovács Peter , van den Brandt Jens , Klöting Ingrid 
Published: June 2007

SUMMARY1. Previous study on the backcross hybrids derived from a cross of the spontaneously hypertensive rat (SHR/Mol) and the spontaneously diabetic BB/OK rat demonstrated the existence of quantitative trait loci (QTL) affecting lipid phenotypes on chromosome 4 and suggestive linkage of lipid phenotypes with markers on chromosome 1. Because the previous study was performed with backcross hybrids at 12 weeks of age and it is known that lipid phenotypes can show age‐related differences, in the present study, the effect of QTL (chromosome 1 and 4) on serum triglycerides and cholesterol was longitudinally analysed between 20 and 32 weeks of age in backcross hybrids.2. The results of the present study show that the effect of QTL on chromosome 4 (between Il‐6 and D4Mit9) for serum triglycerides was maximal at 20 weeks of age, but disappeared at 32 weeks of age. In contrast, the effect of QTL on serum total cholesterol on chromosome 4 (Npy‐Spr) was maximal at 32 weeks of age. In contrast with the first study (12 weeks), the longitudinal investigation showed significant linkage of D1Mit14 marker with lipid phenotypes on chromosome 1.3. The results of the present study indicate the necessity of considering the role of age in QTL analysis of lipid phenotypes.
AUGMENTED EXERCISE PLASMA NORADRENALINE WITH IMPAIRED CHRONOTROPIC RESPONSIVENESS IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY*
Authors: Omodani Hiroki , Kinugawa Toru , Ogino Kazuhide , Furuse Yoshiyuki , Yamaguchi Masako , Mori Masatake , Endo Akihiro , Kato Masahiko , Kato Tatsuo , Osaki Shuichi , Miyakoda Hiroyuki , Igawa Osamu , Hisatome Ichiro , Shigemasa Chiaki 
Published: June 2007

SUMMARY1. There is controversy regarding plasma catecholamine levels in patients with hypertrophic cardiomyopathy (HCM) and few data exist on serial plasma catecholamine measurements during exercise. The present study determined whether cardiovascular and plasma catecholamine responses to exercise were altered in patients with HCM.2. Plasma noradrenaline (NA) and adrenaline were measured at rest, at the end of each stage during exercise and immediately and 5 min after submaximal treadmill exercise in 15 patients with non‐obstructive HCM (13 males, two females; mean (±SEM) age 54 ± 3 years) and in 15 age‐ and sex‐matched controls. The ratio of the increment in heart rate (HR) divided by the increment in plasma NA during exercise (ΔHR/ΔNA) was used as an index of chronotropic sympathetic responsiveness to exercise.3. Exercise duration was shorter (11.2 ± 0.6 vs 8.7 ± 0.6 min for control vs HCM, respectively; P<0.01) and diastolic blood pressure was significantly higher at stages I and II of modified Bruce protocol HCM.4. Resting plasma NA levels (149 ± 17 vs 167 ± 28 pg/mL for control vs HCM, respectively; NS) were not different, but plasma NA levels at stages I and H were significantly higher in HCM than in controls (243 ± 26 vs 399 ± 69pg/mL (P<0.05) and 308 ± 30 vs 548 ± 110pg/mL (P<0.05), respectively).5. Peak plasma NA levels were not significantly higher in HCM than in controls (578 ± 59 vs 918 ± 184 pg/mL, respectively; NS).6. The ratio AHR/ANA was significantly lower in HCM compared with control at stages I and II (0.49 ± 0.10 vs 0.21 ± 0.05 (P<0.05) and 0.38 ± 0.06 vs 0.20 ± 0.05 (P < 0.05), respectively). There were no differences in plasma adrenaline responses during exercise between the two groups.7. Patients with HCM had augmented plasma NA levels during submaximal exercise with a higher diastolic blood pressure response. Chronotropic sympathetic responsiveness was impaired during the early stages of exercise in patients with HCM.
EFFECT OF CROSS‐FOSTERING ON NEONATAL SODIUM BALANCE AND ADULT BLOOD PRESSURE IN THE SPONTANEOUSLY HYPERTENSIVE RAT
Authors: Gouldsborough Ingrid , Ashton Nick 
Published: June 2007

SUMMARY1. The aim of the present study was to compare electrolyte handling in naturally reared neonatal spontaneously hypertensive rats (SHR) with those reared by a Wistar‐Kyoto (WKY) rat foster mother (denoted SHRX), as cross‐fostering SHR pups to a WKY rat dam lowers adult blood pressure in the SHR.2. The electrolyte content of WKY rat and SHR dams’ milk was determined and electrolyte intake and urinary excretion rates were calculated in both naturally reared and cross‐fostered WKY rat and SHR pups.3. The milk sodium concentration fell in both strains (WKY rat: 31.8 ± 2.0 to 15.2 ± 1.2 mmol/L; SHR 31.9 ± 2.5 to 18.2 ± 1.6 mmol/L; P < 0.001), as did potassium (P < 0.001), over lactation, but there were no differences between strains. Calcium and magnesium concentrations increased (P< 0.001), although SHR dam's milk contained less calcium (P < 0.001) than that of WKY rat dams during the third week of lactation.4. Spontaneously hypertensive rat pups ingested less milk (P<0.05) than WKY rat pups; therefore, their cumulative sodium intake over postnatal days 4–15 was significantly lower than that of WKY rat pups (WKY rat vs SHR: 84.4 ± 3.6 vs 59.7 ± 2.6 μmol/g bodyweight, respectively; P < 0.05) and fostered SHRX pups (77.7 ± 7.0 μmol/g bodyweight; P < 0.05). Potassium and magnesium intakes were comparable between SHR, WKY rat and SHRX pups, but SHR pups ingested significantly less calcium than either WKY rat pups (136.1 ± 6.4 vs 200.1 ± 9.5p, mol/g bodyweight, respectively; P<0.05) or SHRX pups (200.0 ± 18.0 μmol/g bodyweight; P<0.05).5. These data show that the neonatal SHR experiences a period of sodium deficiency during the developmental stage when cross‐fostering is effective in lowering blood pressure. This is consistent with the reported up‐regulation of the renin‐angiotensin system observed in SHR at this time and may have a long‐term influence on blood pressure.
MULTIPLE COMPARISON PROCEDURES UPDATED
Authors: Ludbrook John 
Published: June 2007

SUMMARY1. A common statistical flaw in articles submitted to or published in biomedical research journals is to test multiple null hypotheses that originate from the results of a single experiment without correcting for the inflated risk of type 1 error (false positive statistical inference) that results from this. Multiple comparison procedures (MCP) are designed to minimize this risk. The present review focuses on pairwise contrasts, the most common sort of multiple comparisons made by biomedical investigators.2. In an earlier review a variety of MCP were described and evaluated. It was concluded that an effective MCP should control the risk of family‐wise type 1 error, so as to ensure that not more than one hypothesis within a single family is falsely rejected. One‐step procedures based on the Bonferroni or Sidak inequalities do this. For continuous data and under normal distribution theory, so does the Tukey‐Kramer procedure for all possible pairwise contrasts of means and the Dunnett procedure for all possible pairwise contrasts of means with a control mean.3. There is now a new class of MCP, based on the Bonferroni or Šidák inequalities but performed in a step‐wise fashion. The members of this class have certain desirable properties. They: (i) control the family‐wise type 1 error rate as effectively as the one‐step procedures; (ii) are more powerful than the one‐step Bonferroni or Sidak procedures, especially when hypotheses are logically related; and (iii) can be applied not only to continuous data but also to ordinal or categorical data.4. Of the new step‐wise MCP, Holm's step‐down procedures are commended for their combination of accuracy, power and versatility. They also have the virtue of simplicity. Given the raw P values that result from conventional tests of significance, the adjustments for multiple comparisons can be made by hand or hand‐held calculator.5. Despite the corrective abilities of the new step‐wise MCP, investigators should try to design their experiments and analyses to test a single, global hypothesis rather than multiple ones.
CAFFEINE, BUT NOT TIME OF DAY, INCREASES WHOLE‐ARM PHYSIOLOGICAL TREMOR IN NON‐SMOKING MODERATE USERS
Authors: Miller L Stephen , Lombardo Thomas W. , Fowler Stephen C. 
Published: June 2007

SUMMARY1. Consumptive levels of caffeine significantly increased whole‐arm physiological tremor in young adult males at 3 but not 1 mg caffeine/kg bodyweight.2. Physiological tremor was not affected by time of day (TOD) or the interaction of caffeine and TOD.3. Findings suggest that ingestion of a single oral dose of caffeine at typical consumptive levels results in measurable changes in physiological functioning and that whole‐arm physiological tremor is a sensitive measure of physiological change due to drug effects.4. However, the results suggest that whole‐arm physiological tremor may not detect reliably TOD changes in functioning.
THE USE OF KNOCKOUT MICE TO UNDERSTAND THE ROLE OF CYTOKINES IN FEVER
Authors: Kluger Matthew J. , Kozak Wieslaw , Leon Lisa R. , Conn Carole A. 
Published: June 2007

SUMMARY1. In most instances, data obtained using knockout mice to dissect the role of cytokines in fever are similar to data obtained by other, more traditional experimental techniques.2. Interleukin (IL)‐lβ appears to be critically involved in fever caused by some routes of infectiodinflammation (e.g. localized inflammation with turpentine). This cytokine has only a small role in fevers caused by i.p. injection of lipopolysaccharide (LPS). These IL‐lβ‐induced fevers in knockout mice appear to be via the induction of IL‐6, similar to LPS‐induced fevers in rats. Interleukin‐6 also appears to be critically involved in turpentine‐induced fever.3. The precise role of tumour necrosis factor (TNF) in fever is controversial. Data obtained from knockout mice lacking both TNF receptors do not support a pyrogenic role for TNF in fever either to i.p. injection of LPS, s.c. injection of turpentine or following caecal ligation and puncture.4. The roles of these cytokines in fevers induced by injection of LPS, IL‐lβ, turpentine and caecal ligation and puncture are summarized. The data show the complexity of the febrile response. Depending on the types of inflammatoryhnfectious stimuli, different cytokines play important roles. Because other cytokines are thought to be involved in fever (e.g. macrophage inflammatory protein, interferons), considerable work is still needed to dissect the precise roles of cytokines in fever.
ROLE OF ENDOTHELIUM AND K+ CHANNELS IN DOBUTAMINE‐INDUCED RELAXATION IN RAT MESENTERIC ARTERY
Authors: Huang Yu , Kwok Kai Hong , Chan Nickie Wai Kei , Lau Chi Wai , Chen Zhen Yu 
Published: June 2007

SUMMARY1. In order to examine the possible involvement of the endothelium and K+ channel activation in the relaxation induced by dobutamine, a β‐adrenoceptor agonist, in rat isolated mesenteric arteries, the effects of inhibitors of nitric oxide (NO) activity, blockers of K+ channels and high extracellular K+ were studied by measuring isometric tension in both endothelium‐intact and ‐denuded arteries.2. Dobutamine inhibited the phenylephrine (PE)‐induced sustained tension with a pEC50 of 7.40±0.08 in endothelium‐intact arteries. Removal of functional endothelium attenuated the effect of dobutamine. The relaxation induced by dobutamine was inhibited by the β1‐adrenoceptor antagonist CGP20712A (3μ.mol/L) but not by the β2‐adrenoceptor antagonist ICI 118 551 (3 μmol/L) in endothelium‐denuded arteries.3. Pretreatment with NG‐nitro‐l‐arginine (l‐NNA; 100 μmol/L) or methylene blue (3 μmol/L) induced a similar degree of inhibition of the dobutamine‐induced relaxation in endothelium‐intact arteries, while NG‐nitro‐d ‐arginine (100 (μmol/L) and indomethacin (10 μmol/L) had no effect. In contrast, pretreatment with L ‐NNA (100 μmol/L) did not affect the relaxation induced by sodium nitroprusside (SNP) or forskolin. Methylene blue (3μmol/L) inhibited the relaxant response to SNP.4. Charybdotoxin (CTX; 100nmol/L), iberiotoxin (IBX; 100nmol/L) and tetraethylammonium ions (TEA+; 3mmol/L) significantly reduced the dobutamine‐induced relaxation. Tetrapentylammonium ions (TPA+; 5μmol/L) markedly inhibited the relaxant effect of dobutamine. The pECso values for control and in the presence of TPA+ in endothelium‐intact arteries were 7.35±0.11 and 6.14±0.17, respectively, and 6.35±0.09 and 5.87±0.17 for control and in the presence of TPA+ in endothelium‐denuded arteries, respectively. In contrast, glibenclamide (3 μ‐mol/L) was ineffective. At 5 μmol/L, TPA+ also inhibited the relaxation induced by forskolin.5. The maximal relaxation of PE‐contracted arteries induced by 3μmol/L dobutamine was completely abolished in the 60mmol/L K+‐contracted arteries with and without endothelium, while dobutamine at a concentration greater than 3 μmol/L induced inhibition of the high‐K+ response.6. The present results indicate that endothelium, probably NO but not prostacyclin, was involved in the dobutamine‐induced relaxation in rat mesenteric arteries. Activation of CTX‐, IBX‐ and TPA+‐sensitive K+ channels contributed towards the observed relaxation. Loss of the ability to relax the 60 mmol/L K+‐contracted arteries suggests that endothelium‐derived vasoactive factors affected by concentrations of dobutamine less than 3 μmol/L may also act through K+ channels in our preparations. Higher concentrations of dobutamine may have a direct, endothelium‐independent relaxant effect.
EFFECT OF TRANSMUCOSAL FLUID MOVEMENT ON ZINC AND COPPER ABSORPTION FROM THE RAT SMALL INTESTINE
Authors: Kuzuya Takafumi , Hasegawa Takaaki , Ogura Yozo , Nabeshima Toshitaka 
Published: June 2007

SUMMARY1. The effects of transmucosal fluid movement on zinc and copper absorption from rat small intestine were investigated using an in situ recirculating perfusion method.2. Transmucosal fluid movement was obtained by using hypo‐, iso‐ or hyperosmotic perfusate containing various concentrations of sodium chloride. Linear correlations were obtained between net fluid movement and absorption rate constants, which were calculated from the perfusion decline of zinc (n = 15; r= 0.77) and copper (n= 15; r = 0.75).3. The changes in serum levels of these metals did not correlate with the increase in the absorption rate.4. The present study indicates that zinc and copper absorption is dependent on transmucosal fluid movement.
PRODUCTION OF EICOSANOIDS AND ANGIOTENSIN II IN RESISTANCE VESSELS IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Kunimoto Masako , Soma Masayoshi , Kanmatsuse Katsuo 
Published: June 2007

SUMMARY1. Angiotensin II (Angll) and eicosanoids may be important in vascular remodelling and the pressor response via autocrine and paracrine mechanisms. We evaluated the influences of ageing and β‐adrenoceptor stimulation on the production of vascular Angll and eicosanoids in male spontaneously hypertensive rats (SHR), aged 5,17 and 30 weeks, and age‐matched Wistar‐Kyoto (WKY) rats.2. All rats were weighed and their systolic blood pressure (SBP) was measured by the tail‐cuff method. Mesenteric arteries were isolated and perfused with Krebs'‐Henseleit solution. The outflows of prostaglandin E2 (PGE2), 6‐keto‐PGF1α, thromboxane B2 (TxB2) and AngII were measured by specific radioimmunoassays.3. The SBP was higher in SHR than in WKY rats in the 17‐and 30‐week‐old groups and increased with age. Basal levels of PGE2 were significantly lower in SHR than in WKY rats. The ratios of 6‐keto‐PGF1α to TxB2 and PGE2 to TxB2 were significantly lower in 17‐week‐old SHR compared with age‐matched WKY rats. Basal Angll release did not differ between SHR and WKY rats and decreased with age. Isoproterenol stimulated the release of Angll; the magnitude of the increment was greater in WKY rats than in age‐matched SHR. These results show that there is an imbalance in the production of vasodilator and vasoconstrictor eicosanoids in the resistance vessels of SHR at ages at which hypertension developed.4. This imbalance may contribute to the increased vasoconstrictor response and vascular remodelling in SHR. Our findings suggest that vascular Angll plays a role in the ageing process and that β‐adrenoceptor‐stimuIated release of vascular Angll is impaired in SHR.
ROLE OF AFFERENTS IN THE DEVELOPMENT AND CELL SURVIVAL OF THE VERTEBRATE NERVOUS SYSTEM
Authors: Sherrard Rachel M. , Bower Adrian J. 
Published: June 2007

SUMMARY1. During normal development of the vertebrate central nervous system, a considerable number of neurons die. The factors controlling which neurons die and which survive are not fully understood.2. Target populations are known to maintain their innervating neurons. However, the role of afferents in maintaining their targets is still under review.3. In the developing nervous system, deafferentation of a neuron population is difficult to achieve because plasticity (structural re‐organization) can cause re‐innervation of the area. Re‐innervation alters, rather than removes, the afferent supply.4. Afferent input is important for neuronal survival during development because deafferentation increases neuronal death by 20‐30% and increasing input diminishes neuronal death.5. Deafferented neurons die at the normal time for cell death for any given population. This occurs after the arrival of afferent axons but before the completion of connectivity and the onset of unction.6. Neuronal survival is maintained by any input, such as reinnervation by inappropriate fibres, but for optimal survival, morphological maturation and the acquisition of normal physiology, the correct input is required.7. Afferents maintain their target neurons via a combination of electrical activity and delivery of trophic agents, which adjust intracellular calcium, thereby facilitating protein synthesis, mitochondrial function and suppressing apoptosis.8. Evidence from animal and in vitro experiments indicates that afferents play an extremely important role in the survival of developing neurons in the immature vertebrate nervous system.
INHIBITORY MECHANISMS OF NALOXONE ON HUMAN PLATELETS
Authors: Sheu Joen‐Rong , Lee Yen‐Mei , Lee Ling‐Wen , Luk Hsiang‐Ning , Yen Mao‐Hsiung 
Published: June 2007

SUMMARY1. In the present study, naloxone was tested for its antiplatelet activities in human platelet‐rich plasma (PRP). In human PRP, naloxone (0.1‐0.5 mmol/L) inhibited aggregation stimulated by a variety of agonists (i.e. collagen, adenosine diphosphate (ADP), U46619 and adrenaline).2. Naloxone (0.1‐0.5 mmol/L) did not significantly affect cyclic adenosine monophosphate and cGMP levels in human washed platelets, whereas naloxone (0.5 mmol/L) significantly inhibited thromboxane B2 formation stimulated by collagen (5 μg/mL| in human washed platelets.3. Naloxone (0.5 mmol/L) significantly inhibited [3H]‐inositol monophosphate formation of [3H]‐myoinositol‐loaded platelets stimulated by collagen and U46619. Moreover, naloxone did not influence the binding of 125I‐triflavin to platelet membranes. Triflavin is an Arg‐Gly‐Asp‐containing specific fibrinogen receptor antagonist.4. Addition of naloxone (0.5 mmol/L) to platelet preparations tagged with diphenylhexatriene (DPH) resulted in a considerable decrease in relative fluorescence intensity.5. It is suggested that the anti‐platelet effects of naloxone may be caused, at least partly, by the induction of conformational changes in the platelet membrane initially, followed by the inhibition of thromboxane A2 formation and phosphoinositide breakdown of platelets stimulated by agonists.
PYRROLIDINE DITHIOCARBAMATE IMPROVES THE SEPTIC SHOCK SYNDROMES IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Hong Hong‐Jye , Wu Chin‐Chen , Yen Mao‐Hsiung 
Published: June 2007

SUMMARY1. The aim of the present study was to evaluate the effect of pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor‐kB (NF‐kB), on septic shock induced by Escherichia coli lipopolysaccharide (LPS) in spontaneously hypertensive rats (SHR).2. After injection of LPS in SHR, a marked decrease in blood pressure was observed at 3h and vascular hyporeactivity to noradrenaline (NA) was observed after 1 h. A marked increase in plasma levels of tumour necrosis factor‐et (TNF‐α) and nitrite (an indicator of nitric oxide) was also observed in SHR.3. The delayed hypotension and hyporeactivity to NA induced by LPS were significantly reversed by pretreatment of rats with PDTC (10mg/kg). The increase in plasma levels of TNF‐α and nitrite in LPS‐treated groups was also significantly suppressed by PDTC pretreatment. In addition, the survival time of SHR treated with LPS was significantly prolonged by PDTC pretreatment.4. The present ex vivo study demonstrates that the NA‐induced contraction is attenuated and the l‐arginine‐induced relaxation is enhanced in aortic rings obtained from LPS‐treated SHR. Both the reduction of the NA‐induced contraction and the increase of l‐arginine‐induced relaxation were reversed by pretreatment with PDTC. However, the relaxation elicited by acetylcholine (ACh) was not affected in LPS‐treated SHR when compared with sham‐operated SHR. In addition, the ACh‐induced relaxation in LPS‐treated SHR was not affected by PDTC pretreatment.5. In normotensive Wistar‐Kyoto (WKY) rats, LPS had mild effects on blood pressure, vascular hyporeactivity and plasma levels of TNF‐α and nitrite. At a higher doses, PDTC (10 mg/kg) also prolonged survival time and improved haemodynamics in LPS‐treated WKY rats. In the ex vivo study, it was noted that the relaxation elicited by ACh was significantly (P<0.05) attenuated in LPS‐treated WKY rats. This attenuation of the ACh‐induced relaxation by LPS in WKY rats was significantly reversed by pretreatment with 10 mg/kg PDTC.6. In conclusion, PDTC prolongs survival time in rats with endotoxaemia and improves the septic shock syndromes both in vivo and ex vivo. Thus, we propose that PDTC may be of use in septic patients.
RESPONSES OF RAT HIPPOCAMPAL SLICES IN A HIGH‐K+ MEDIUM FOLLOWING IN VIVO GLOBAL ISCHAEMIA
Authors: El‐Sabban F. , Reid KH , Jr HL Edmonds 
Published: June 2007

SUMMARY1. We hypothesized that burst activity induced in rat hippo‐campal tissue by a high‐K+ medium in vitro would be increased by a previous episode of global ischaemia, severe enough to induce persistent neurological dysfunction.2. Male Wistar rats that were subjected to 9 min of chest compression, sufficient to reduce blood pressure (BP) to zero, showed evidence of neurological damage attributed to a global ischaemic insult. Hindlimb function was impaired for 24‐48 h and a susceptibility to sound‐induced seizures was induced in 25 of 35 rats. The seizure susceptibility cleared spontaneously within 2 weeks in 10 of 25 rats.3. Hippocampal slices from postischaemic rats were prepared, tested for viability and were then exposed to an 8.0 mmol/L K+ artificial cerebrospinal fluid in vitro. Spontaneous epileptiform bursting activity in the high‐K+ medium was not increased. Instead, burst size decreased with time after ischaemia.4. The decrement in bursting activity is attributed to loss of cellular activity or integrity. These changes correlate with functional changes described by others, but not necessarily to histologically verifiable cell death. The time course of these changes was remarkably long, continuing for almost 3 weeks. Thus, a less‐than‐lethal ischaemia appears to induce neuronal changes, possibly reversible, that continue for at least 20 days after the global ischaemic insult.