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Biomedical subjects

B Lemmer

Publications and source records attributed to B Lemmer.

At least 73 records · Page 4Linked to original sources
PubMed1996

Diurnal and seasonal changes in sympathetic signal transduction in cardiac ventricles of European hamsters.

This investigation of the relationship between cardiac beta-adrenoceptors and adenosine 3',5'-cyclic monophosphate (cAMP) formation in cardiac ventricles of the nocturnally active European hamster both during euthermia under a 12:12-h dark-light cycle and during hibernation under constant-darkness conditions showed that neither the densities, affinities, nor distribution of the beta 1- and beta 2-receptor subtypes differed between the dark phase, light phase, and hibernation. Basal formation of cAMP by the cardiac adenylyl cyclase of euthermic hamsters was higher in ventricles obtained at night [core temperature (Tcore) = 37.8 degrees C] than in ventricles obtained during the day (Tcore = 36.4 degrees C). Basal formation of cAMP was also significantly lower in hibernating hamsters (Tcore = 7.0 degrees C) than in euthermic hamsters. When adenylyl cyclase activity was stimulated by isoprenaline, guanylylimidodiphosphate [Gpp(NH)p], or forskolin, the rank order of potency was the same in euthermic hamsters and hibernating hamsters: isoprenaline < Gpp(NH)p < forskolin. Functional competition curves indicated that in the euthermic hamsters beta 1-receptors were responsible for 67% of the response to isoprenaline at night and 62% of the response during the day. In hibernating hamsters, in contrast, most of the response to isoprenaline (58%) was mediated via beta 2-receptors. This shift in the relative importance of the receptor subtypes may facilitate arousal from hibernation by making the heart more sensitive to circulating epinephrine.

Adenylyl Cyclases↗
PubMed1996

Circadian rhythms in renal function in hypertensive TGR(mRen-2)27 rats and their normotensive controls.

Patients with secondary hypertension frequently display abnormal circadian blood pressure profiles, characterized by a failure to decrease blood pressure at night. The transgenic TGR(mRen-2)27 rat strain, developing fulminant hypertension after the mouse salivary Ren-2 renin gene has been integrated into its genome, provides a fundamental model of genetic hypertension. Because of an inverse circadian blood pressure profile and an unchanged rhythmic pattern of heart rate compared with the normotensive Sprague-Dawley (SPR) strain, it was proposed to serve as an animal model of genetic hypertension. It was the aim of the present study to investigate the circadian rhythmicity in renal function of the transgenic rat to determine whether hypertension and disturbed circadian blood pressure profile would affect kidney function. Urinary water, electrolyte, and protein excretion, as well as glomerular filtration rate and renal plasma flow, were determined in unrestrained freely moving transgenic hypertensive (TGR) and SPR normotensive control rats by collecting urine and arterial blood every 4 h. Significant and similar circadian rhythms were found in renal excretion and hemodynamics in both normotensive and hypertensive strains. Peaks occurred in the active dark period, whereas troughs were found in daytime for all parameters. However, it has to be pointed out that, although the circadian profiles were not grossly perturbed in hypertensive animals, some small differences between SPR and TGR strains did exist in renal function. These discrepancies were precisely related to acrophase, showing a slight phase delay, and also to relative amplitude in TGR. This study demonstrates that the inverted circadian blood pressure profile affected only slightly the circadian rhythms in kidney function in TGR compared with SPR. These findings support the notion that time-dependent changes in systemic blood flow may be of greater importance for circadian regulation of kidney function than systemic blood pressure.

Animals↗
PubMed1996

Differential effects of antihypertensive drugs on circadian rhythm in blood pressure from the chronobiological point of view.

REVIEW IN DEPTH: The cardiovascular system is well organized in time. The blood pressure normally displays a circadian rhythm characterized by a nightly drop which, however, can be disturbed by disease. The 24 h blood pressure and its mechanisms of regulation are very dynamic and rhythmic processes. Ambulatory blood pressure monitoring data should, therefore, be analysed by more subtle methods than linear or cosinor analysis. The blood pressure lowering effects and the dose-reponse relationship of antihypertensive drugs can also be circadian phase-dependent. Antihypertensive drug treatment should not only aim to lower blood pressure but also to achieve a normal 24 h blood pressure pattern. Finally, when evaluating the duration of action it is mendatory to register the blood pressure by ambulatory monitoring for more than 24 h.

Journal Article↗
PubMed1996

ABPM-FIT and CV-SORT: an easy-to-use software package for detailed analysis of data from ambulatory blood pressure monitoring.

We describe a non-profit software package for the computerized analysis of ambulatory blood pressure monitoring (ABPM) recordings, in order to make it available to researchers in cardiovascular physiology, pharmacology and medicine. The first program, ABPM-FIT, can load data from several ABPM devices directly as they are stored on disk, making complicated data conversion steps unnecessary. The program performs conventional linear analyses of ABPM data automatically by calculation of mean, SD, load (the percentage of data above a chosen limit), and highest and lowest readings in user-defisned day and night periods. In addition, the area under the parameter-time curve (AUC) and the weighted mean (AUC/time) is calculated for all parameters monitored. In a second step, ABPM-FIT performs a rhythm analysis by fitting partial Fourier series to the data. Only those hormonics are included which significantly reduce the residual variance of the fit. The parameters of these functions (mesor, amplitudes, acrophases), values derived from the composed curves (maximum and minimum, AUC) and their slopes (e.g. maximal increase and decrease) are calculated automatically and, if desired, saved on disk. The second program, CV-SORT, loads groups of result files saved by ABPM-FIT, allows the extraction of parameters of interest for further analyses and creates spreadsheets containing the selected values from groups of patients. In addition, CV-SORT performs simple statistics, and calculates group mean circadian blood pressure and heart rate profiles from individual Fourier curves, with SD, confidence intervals or percentiles. The features of both programs are shown in exemplary analyses of ABPM recordings.

Journal Article↗
PubMed1996

Office hypertension: abnormal blood pressure regulation and increased sympathetic activity compared with normotension.

BACKGROUND: The percentage of patients with office or white-coat hypertension has been reported in international studies to be 20-30% of the hypertensive population. These patients can be identified and distinguished from patients with established hypertension by ambulatory blood pressure monitoring (ABPM) or self-measurement. There is still no satisfactory explanation for the phenomenon of 'office hypertension' and there are no data available to show how the blood pressure behaviour of office hypertensives differs from that of normotensive subjects away from the physician's office or clinic environment. OBJECTIVE: To investigate the blood pressure behaviour of patients with office hypertension away from the clinical setting over a 24 h period and to compare it with that of normotensive subjects. DESIGN AND METHODS: The blood pressure and heart rate of 36 patients with office hyhpertension and 33 normotensive subjects matched for age and sex were measured in a hypertension outpatient clinic and over 24 h using ABPM. The ambulatory data were subjected both to conventional and to modern rhythm analysis. Urinary catecholamine excretion was measured as a marker of sympathetic activity. RESULTS: In the clinic, the patients with office hypertension had significantly (P < 0.01) higher blood pressure values (146/97 mmHg) than did the normotensive controls (128/81 mmHg). The conventional analysis as well as the rhythm analysis of the ABPM data revealed no difference between the two groups with respect to the 24 h, daytime or night-time mean values and SD. However, the rhythm analysis showed a higher maximum and a lower minimum value for systolic and diastolic blood pressures in the patients with office hypertension, resulting in a greater amplitude both of systolic and of diastolic blood pressure due to a significantly (P < 0.005 and P < 0.05) higher maximum minus minimum value (38/32 mmHg) compared with those of normotensive controls (29/28 mmHg). The early morning rise in systolic and diastolic blood pressures was significantly (P < 0.008 and P < 0.03) greater in the patients with office hypertension (11/9 versus 7/7 mmHg) and intersected the curve of the normotensive controls at approximately 0600 h. No significant differences in heart rate at any time were observed between the groups. The urinary excretion of noradrenaline and dopamine was significantly (P < 0.01 and P < 0.05) increased during daytime for the office hypertensives. CONCLUSION: Patients with office hypertension, who by definition do not yet have established hypertension, already exhibit abnormal regulation both of systolic and of diastolic blood pressure during the morning period and daytime, with a significantly greater early morning rise compared with normotensive subjects and a greater blood pressure amplitude (amplitude hypertension) due to lower blood pressure during night-time and higher blood pressure during the day with increased sympathetic activation. Office hypertension seems to be the earliest manifestation of hypertension.

Journal Article↗
PubMed1996

Nocturnal blood pressure elevation in transplanted pediatric patients.

Ambulatory blood pressure monitoring during 24 hours was applied in 34 pediatric patients aged 6.3 to 24.3 (median 14.0) years who had been transplanted 0.3 to 8.4 years previously. The mean arterial blood pressure levels measured during the daytime and at night correlated positively (r = 0.70), but 14 of the 28 patients with nocturnal hypertension were normotensive during the day. A reduced nocturnal dip (< 5.5%) of mean arterial blood pressure was detected in 11 of 34 patients. In the first year post-transplantation 4 of 7 patients had an attenuated dip without any obvious cause. Beyond the first year a reduced dip was always associated with a renal pathology. In conclusion, a high prevalence of nocturnal hypertension was detected in grafted pediatric patients, even in presence of normal daytime blood pressures. An attenuated nocturnal dip was found in association with an underlying renal pathology or within the first post-transplant year.

Adolescent↗
PubMed1995

Efficiency of beta-adrenoceptor subtype coupling to cardiac adenylyl cyclase in cardiomyopathic and control hamsters.

Densities of beta-adrenoceptor subtypes and their contributions to stimulation of adenylyl cyclase were studied in heart ventricles from cardiomyopathic (BIO 8262) and control Syrian hamsters (CLAC) at 4 different ages: 30, 100, 200, and 300 days. In BIO ventricles neither total beta-adrenoceptor density nor that of the beta 1-adrenoceptor subtype differed from the controls, whereas the density of beta 2-adrenoceptors was significantly higher in myocardium from 200- and 300-day-old BIO compared to that from age-matched CLAC hamsters. Stimulation of adenylyl cyclase by the non-selective beta-adrenoceptor agonist isoprenaline did not differ between strains, but the beta 1-adrenoceptor mediated component was significantly reduced in cardiomyopathic hamsters of all age groups. In 300-day-old animals beta 1-adrenoceptors accounted for 83% (CLAC) and 68% (BIO) of total beta-adrenoceptor binding sites, whereas only 26% (CLAC) and 6% (BIO) of the isoprenaline effect on cAMP formation were mediated via beta 1-adrenoceptors. Thus, the present study shows a lower coupling efficiency of beta 1-adrenoceptors compared to the beta 2-adrenoceptor subtype in ventricles from healthy Syrian hamsters and a progressive, further reduction in beta 1-adrenergic function in cardiomyopathic animals.

Adenylyl Cyclases↗
PubMed1995

Clinical chronopharmacology: the importance of time in drug treatment.

Nearly all functions of the body, including those influencing pharmacokinetic parameters such as drug absorption and distribution, drug metabolism and renal elimination, show significant daily variations: these include liver metabolism, hepatic blood flow and the first-pass effect; glomerular filtration, renal plasma flow and urine volume and pH; blood pressure, heart rate and organ perfusion rates; acid secretion in the gastro-intestinal tract and gastric emptying time. The onset and symptoms of diseases such as asthma attacks, coronary infarction, angina pectoris, stroke and ventricular tachycardia are circadian phase dependent. In humans, variations during the 24 h day in pharmacokinetics (chrono-pharmacokinetics) have been shown for cardiovascularly active drugs (propranolol, nifedipine, verapamil, enalapril, isosorbide 5-mononitrate and digoxin), anti-asthmatics (theophylline and terbutaline), anticancer drugs, psychotropics, analgesics, local anaesthetics and antibiotics, to mention but a few. Even more drugs have been shown to display significant variations in their effects throughout the day (chronopharmacodynamics and chronotoxicology) even after chronic application or constant infusion. Moreover, there is clear evidence that even dose/concentration-response relationships can be significantly modified by the time of day. Thus, circadian time has to be taken into account as an important variable influencing a drug's pharmacokinetics and its effects or side-effects.

Circadian Rhythm↗
PubMed1995

Ambulatory blood pressure monitoring in paediatric patients treated by regular haemodialysis and peritoneal dialysis.

Ambulatory blood pressure monitoring (ABPM) has been shown to be more representative of blood pressure (BP) levels than casual BP measurements in adult patients treated by haemodialysis (HD). In this study we compared ABPM using the oscillometric SpaceLabs 90207 monitor with casual BP measurements in 35 paediatric patients [17 treated by peritoneal dialysis (PD) and 18 by HD]. Heart rate and plasma concentrations of atrial natriuretic peptide were also measured. No correlations were found between ABPM and causal BP measurements, except for systolic day-time BP in PD patients (r = 0.63). Seventy percent of PD and 33% of HD patients were regarded as hypertensive when evaluated by ABPM, while casual BP measurements demonstrated hypertension in 47% (P < 0.05) of PD patients and in 44% (NS) of HD patients. One-third of patients were reclassified by ABPM either from normotensive to hypertensive (7/19) or from hypertensive to normotensive (5/16). BP assessed by ABPM was higher in PD than in HD patients. The physiological decline of BP at night was significant and more pronounced in PD than in HD patients. In HD patients day-time BP did not differ between the 1st and the 2nd interdialytic day, but increased in the night hours before the following dialysis session. A positive correlation was found between day-time BP and pre-dialysis plasma atrial natriuretic peptide in both treatment groups. In conclusion this study demonstrates that casual BP recordings are not representative of average BP in dialysed paediatric patients. ABPM is useful in the diagnosis and treatment of hypertension in children with end-stage renal disease.

Adolescent↗
PubMed1995

Mechanisms of the circadian regulation of beta-adrenoceptor density and adenylyl cyclase activity in cardiac tissue from normotensive and spontaneously hypertensive rats.

Circadian variation in beta-adrenoceptor density and adenylyl cyclase activity was studied in myocardium from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In SHR cardiac beta-adrenoceptor density was significantly lower than in WKY. This reduction in total beta-adrenoceptors was exclusively due to a loss in the beta 1-subtype. Total and beta 1-adrenoceptor density in ventricles from both strains exhibited significant circadian variation with peaks occurring in the middle of the light and dark periods, whereas the beta 2-subtype did not show rhythmicity. Similarly, stimulation of adenylyl cyclase via total beta-adrenoceptors and via the beta 1-subtype was circadian time dependent, but circadian peaks occurring at the beginning of the light and dark periods were 6 h apart from those in beta-adrenoceptor density. Rhythmicity in the formation of cAMP was observed under basal conditions and after stimulation by isoprenaline or a forskolin derivative, whereas addition of manganese-ions abolished the circadian variation. In conclusion, the present study demonstrates that in ventricular tissue from WKY and SHR circadian rhythms observed in total beta-adrenoceptor density are due exclusively to variations in the beta 1-subtype. Since peaks in cAMP formation coincided with troughs in beta-adrenoceptor number, cAMP mediated phosphorylation of beta-adrenoceptors enhancing their down-regulation, could be involved in the circadian regulation of myocardial beta-adrenoceptor density. Rhythmicity in cAMP formation itself seems to involve coupling of G-proteins, because manganese ions abolished the circadian variation.

Adenylyl Cyclases↗
PubMed1995

Effects of the angiotensin II receptor antagonist losartan on 24-hour blood pressure profiles of primary and secondary hypertensive rats.

Primary and secondary hypertension differ with regard to circadian blood pressure (BP) profiles. To evaluate the contribution of the renin-angiotensin system (RAS) to circadian BP regulation, we studied cardiovascular effects of the angiotensin II (AII) receptor antagonist losartan and the angiotensin-converting enzyme (ACE) inhibitor enalapril in animal models of primary and secondary hypertension after morning and evening dosing. Systolic/diastolic BP (SBP/DBP) and heart rate (HR) were measured telemetrically in spontaneously hypertensive rats (SHR) and transgenic hypertensive rats (TGR[mRen-2]27). Losartan (0.3 to 30 mg/kg) or enalapril maleate (10 mg/kg) were injected intraperitoneally (i.p.) either at 0700 or 1900 h. Baseline SBP/DBP and HR showed significant circadian rhythmicity in both strains. The 24-h means in SBP/DBP were 190/127 mm Hg in SHR and 200/139 mm Hg in TGR. TGR showed a reversed circadian profile in BP, with peaks occurring during the daily resting period, whereas HR peaked at night. Losartan reduced BP dose dependently; reductions in TGR were significantly greater and obtained at 30-fold lower doses than in SHR. Maximum decreases induced by losartan were similar to those induced with enalapril 10 mg/kg. Both drugs reduced BP in TGR more effectively when applied at 0700 than at 1900 h, resulting in a normalized circadian BP profile. Our results demonstrate that the RAS is involved in both the pathomechanism of hypertension and in the inverse circadian BP pressure pattern in TGR.

Angiotensin II↗
PubMed1995

The efficacy of a nursing challenge to patients: testing a new intervention to decrease self-harm behaviour in severe personality disorder.

This paper describes the study of a new intervention, which was intended to increase therapeutic engagement with patients and to decrease self-harm behaviour. As a result of nursing observations in a unit that specialized in severe personality disorders, a psychodynamic perspective to treatment was introduced in the form of a nursing challenge. The intervention was evaluated in a new service for young adults at a psychiatric hospital in the south of England, as part of a clinical research apprenticeship. The care and treatment of persons with severe personality disorders present a major challenge to coherent and cohesive teamwork. A test and retrospective comparison study is described and its findings reported. Data from the study point to the need for more than a single challenge, to achieve a sustained reduction in self-harm, along with staff training to ensure working knowledge of a particular framework.

Adult↗
PubMed1995

Circadian rhythms of dopamine and cholecystokinin in nucleus accumbens and striatum of rats--influence on dopaminergic stimulation.

The concentrations of cholecystokinin (CCK) and dopamine (DA) were determined in the nucleus accumbens (anterior, posterior) and striatum of rats every 2 h during a period of 24 h. For both substances, a circadian rhythm was found, which was best fitted by a dominant 24-h period superimposed by the second (12 h) and fourth (6 h) harmonics. The rhythms in CCK and DA were negatively correlated because of a difference in phase position by approximately 3 h. A dominant DA peak was found in the light phase coinciding with a trough in CCK and vice versa in the dark phase. Based on these data, CCK and DA were determined in rats treated with gamma-butyrolactone (GBL; inhibitor of DA release) or thyrotropin-releasing hormone (TRH; stimulator of DA release) at 0900 h or 1300 h to study a putative time-dependency in drug effects. After GBL treatment, CCK as well as DA increased by up to 200% whereas TRH administration led to a rather complex alteration, inasmuch as CCK was increased or decreased, depending on circadian time, whereas the rhythmic pattern in DA remained relatively unaffected. Comparing the drug effects obtained at 0900 h with the response seen at 1300 h revealed significant quantitative as well as qualitative differences. The results demonstrate that the neurotransmission system investigated changed its level of activity depending on time of day. No changes were obtained that convincingly may be ascribed to colocalization of DA and CCK. It is concluded that the chronobiological data indicate a close interaction of CCK and DA in various areas of the rat brain, independent of colocalization.

4-Butyrolactone↗
PubMed1995

[Chronobiology and chronopharmacology of cardiovascular diseases].

Physiological functions as well as pathophysiological events--angina pectoris, myocardial infarction, sudden cardiac death--display pronounced circadian rhythms. Clinical studies also give evidence for a circadian phase dependency in the pharmacokinetics of cardio-vascular active drugs. Thus, a circadian phase dependency in the dose-response relationship of drugs has to be taken into account.

Animals↗
PubMed1995

Contribution of the nitric oxide-guanylyl cyclase system to circadian regulation of blood pressure in normotensive Wistar-Kyoto rats.

OBJECTIVES: The study was performed in order to elucidate whether or not the nitric oxide-guanylyl cyclase system is involved in the circadian regulation of blood pressure. METHODS: Basal and sodium nitroprusside-stimulated guanylyl cyclase activity was studied in vitro in aortic tissue from normotensive Wistar-Kyoto rats sacrificed at 7 circadian times. Effects of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on blood pressure and heart rate of rats were measured telemetrically after acute injection of L-NAME either in the morning or in the evening as well as after chronic application in drinking water. RESULTS: Guanylyl cyclase activity exhibited significant circadian rhythmicity under basal conditions and after stimulation by sodium nitroprusside 10 microM. Peaks in cGMP formation were observed in the daily resting period, i.e. the period of low blood pressure in rats. Acute application of L-NAME dose-dependently increased blood pressure; effects were more pronounced after injection in the morning than in the evening, leading to an inverse blood pressure profile after the highest dose (30 mg/kg i.p.). Chronic treatment with L-NAME resulted in a dose-dependent upward shift of the control blood pressure profile. Only at the highest dose applied in drinking water (100 mg/kg per day) was the circadian pattern in blood pressure altered, showing a reduced fall in the morning. CONCLUSIONS: Circadian rhythmicity in basal and stimulated soluble guanylyl cyclase activity and the reversed blood pressure profile after acute injections of L-NAME indicate an involvement of the nitric oxide-guanylyl cyclase system in circadian blood pressure regulation. After chronic inhibition of nitric oxide synthase additional and counterregulatory mechanisms have to be considered.

Animals↗
PubMed1994

Adenylyl cyclase activity in Alzheimer's disease brain: stimulatory and inhibitory signal transduction pathways are differently affected.

Adenylyl cyclase (AC) activity was studied in post mortem hippocampus and cerebellum from eight patients with Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) and seven non-demented control patients. AC was stimulated via stimulatory guanine nucleotide binding proteins (Gs) using guanosine triphosphate (GTP) and GppNHp (both 10(-4) M) or directly with either forskolin (10(-4) M) or Mn2+ (10(-2) M). Inhibition of AC via A1-receptors was performed with N6-cyclohexyladenosine (CHA) under basal conditions and in the presence of forskolin (10(-5) M). In both brain regions AC activity was significantly reduced in AD/SDAT when compared to controls. Under basal conditions and after stimulation via Gs mean reduction in hippocampus and cerebellum was 47.7% and 58.2%, respectively. The reduction was less pronounced after direct activation of the AC, amounting to 21.8% in hippocampus and 28.1% in cerebellum. CHA inhibited basal and forskolin-stimulated AC concentration-dependently by about 20% (basal) and 30% (forskolin). Inhibition by CHA was similar in hippocampus and cerebellum and tended to be more pronounced in AD/SDAT than in controls. Since the reduction of AC activity in AD/SDAT is greater after stimulation via Gs than after direct activation of the catalytic subunit, we suggest that both Gs and the catalytic subunit seem to be impaired. The fact that CHA-mediated inhibition of AC is not significantly different in AD/SDAT and controls, indicates that in contrast to Gs-, inhibitory G-proteins (Gi) coupling to AC remains intact in Alzheimer's disease.

Adenosine↗
PubMed1994

Effects of bright light on circadian patterns of cyclic adenosine monophosphate, melatonin and cortisol in healthy subjects.

Bright light is known as a strong zeitgeber on human circadian rhythms and influences several endocrine and neuroendocrine functions. In the present study we examined the influence of a 3-h bright light stimulus, given at different times during the day (morning or evening), on circadian patterns of cyclic adenosine monophosphate (cAMP), melatonin and cortisol. Two groups of synchronized healthy volunteers (lights on: 05.00-23.00 h) were exposed to bright light (2500 lux) for 3 h over 6 days either in the morning (05.00-08.00 h) or in the evening (18.00-21.00 h). The results showed a significant phase advance in the circadian rhythms of melatonin and cortisol when bright light was given in the morning but not when given in the evening. Rhythm in plasma cAMP basically was not affected by either light treatment.

Adult↗