Chronobiologic Evaluation of Drug Efficacy in Hypertension

Time-associated variations of blood pressure became accesible due to the modern development of pressure monitoring technology. The data collection and analysis should be standardized and formulated. Time-associated changes of pressure were evaluated not only by nonparametric and conventional but also by parametric and rhythmometric estimation. The reference data (chronodesms) are essential to define the deviant magnitude of pressure. This chronobiologic approach became feasible to quantitate the efficacy of antihypertensive agents in hypertensives.     

Determinants of gas flow through a bronchopleural fistula

To assess the determinants of bronchopleural fistula (BPF) flow, we used a surgically created BPF to study 15 anesthetized intubated mechanically ventilated New Zealand White rabbits. Mean airway pressure and intrathoracic pressure were evaluated independently. Mean airway pressure was varied (8, 10, or 12 cmH2O) by independent manipulations of either peak inspiratory pressure, positive end-expiratory pressure, or inspiratory time. Intrathoracic pressure was varied from 0 to -40 cmH2O. BPF flow varied directly with mean airway pressure (P less than 0.001). However, at constant mean airway pressure, BPF flow was not influenced independently by changes in peak inspiratory pressure, positive end-expiratory pressure, or inspiratory time. Resistance of the BPF increased as intrathoracic pressure became more negative. Despite increased resistance, BPF flow also increased. BPF resistance was constant over the range of mean airway (P less than 0.01) pressures investigated. Our data document the influence of mean airway pressure and intrathoracic pressure on BPF flow and suggest that manipulations which reduce transpulmonary pressure will decrease BPF flow.     

Pressure-induced unfolding of lysozyme in aqueous guanidinium chloride solution.

The pressure-induced unfolding of lysozyme was investigated in an aqueous guanidinium chloride solution by means of ultraviolet spectroscopy. Assuming a two-state transition model, volume changes were calculated from the slope of free energy vs. pressure plots over a temperature range of 10 to 60 degrees C. Between 25 and 60 degrees C, almost constant volume changes were observed in the transition region, which was reflected in almost identical slopes of the free energy change vs. pressure plots. On the other hand, the different slopes were observed in the pressure dependence of free energy change at temperatures lower than 25 degrees C. These data were interpreted as suggesting that a two-state model is not appropriate at low temperature, but instead one or more intermediates are present under these conditions. The volume changes for unfolding became less negative at temperatures higher than 25 degrees C.     

Elastic characteristics of the airway wall

To examine the elastic behavior of the upper airway, we obtained pressure-area plots from data gathered from acoustic images of the airway and measurements of mouth pressure during tidal breathing in 10 adult human volunteers (dA/dP). These plots revealed both tidal hysteresis and a change in slope as a function of distance along the airway. The slope of the regression line of the dA/dP plots decreased from the pharyngeal region to the trachea and became 0 at the thoracic inlet, the location of which was independently assessed. In most subjects the slope became negative distal to the thoracic inlet. Correlation coefficients between pressure and area approached 1 in the pharyngeal region and 0 at the thoracic inlet. When subjects breathed against a small resistive load (10 cmH2O.1(-1).s) pharyngeal, extrathoracic, and intrathoracic pressure-area plots were exaggerated but the slope at the thoracic inlet was unchanged. We conclude that this pressure-area characteristic defines regional differences in upper airway elasticity and delineates the transition point between the intra- and extrathoracic airways.     

Diabetes insipidus and exogenous antidiuretic hormone activity modifications by lithium in the rat]

The authors made conspicuous in the rat the appearance of "diabetes insipidus" induced by two lithium salts: chloride and carbonate administered orally, with increasing doses in food. The polyuria, polydipsia and urinary hypotony are reversible and disappeared with stopping the treatment. The animals became insensible to the exogenous antidiuretic hormon during the treatment and progressively became sensible again during the following twenty days so suggesting a nephrogenic mechanism by lithium: either a loss of ADH activity, either the abolition of intrarenal osmotic pressure gradient.     

Effects of pressure stimulation of the body surface on placing reactions

The effects of pressure stimulation of the body surface on placing reactions were investigated in intact unanesthetized cats. A slight contact applied to the dorsum of the fore- and hindpaws produced the typical placing reactions in these preparations. These reflexes, however, became more prominent if, in addition to the exteroceptive input, a proprioceptive input was elicited after plantar flexion of the paws. Slight pressure applied to the upper part of the body greatly depressed not only tactile placing reactions, but also to a lesser extent proprioceptive placing reactions. Moreover, these reflexes were less prominent and more sluggish and fatiguable than in the normal cats. The depression of the placing reactions elicited by the cutaneous input during pressure applied to the body surface mainly affected the forelimbs. However, as soon as the pressure stimulation was removed, the placing reactions reappeared or became as prominent as usual. We postulate that the exteroceptive input resulting from body pressure decreased the placing reactions by exciting the Purkinje cells of the intermediate cortex of the cerebellum, which are in turn inhibitory on the interpositus nucleus, thus reducing the neuronal discharge of the interpositorubrospinal pathway acting on flexor motoneurons.     

Genetic control of blood pressure in spontaneously hypertensive rats (SHR)

Genetic control of blood pressure in the SHR strain was studied by three separate experiments which consist of cross analysis between the SHR and Donryu, two-way selecton for high and low blood pressure levels, and successive backcrosses to the parental strains. The results obtained were as follows. 1. The data from genetic crosses between the SHR and Donryu showed the phenotype segregation ratio of 1:1 at the backcross and 1:2:1 at the F2 generation. 2. Two-way selection for high and low blood pressure levels was performed from the F2 generation onward. The separation between the two lines occurred immediately after the first selection. Thereafter, the difference increased gradually with generation. The blood pressure level at the seventh generation of selection became approximately equal to those of the parental strains. 3. Two types of the successive backcross were performed from the F1 hybrids by mating the males showing the highest blood pressure level to Donryu females and the females showing the lowest blood pressure level to SHR males on the other. Bimodality was observed in the distribution of blood pressure levels at each generation. Their phenotypic segregation ratios were accordant with 1:1 on the whole. At the intercross generation during successive backcrosses, a trimodal distribution was observed. 4. These results confirmed that the hypertensive trait of the SHR is regulated by a single major gene and other several genes with minor effect. A gene symbol ht was proposed for this major gene. Concurrently, a congenic strain having the ht gene on the genetic background of the Donryu was developed by the successive backcross system.     

Canine coronary venous pressures: responses to positive inotropism and vasodilation

The epicardial coronary venous pressure in 16 dogs was compared with coronary arterial pressure as well as aortic, intraventricular, and intramyocardial pressures. Partial aortic occlusion augmented intraventricular (IVP), intramyocardial (IMP), aortic (AP), and coronary arterial pressures. Peripheral coronary venous pressure was also elevated. Dobutamine significantly augmented IVP and IMP but not aortic or central coronary artery pressures; this agent significantly elevated coronary venous systolic pressure (28/8 to 84/12 mmHg) (1 mmHg = 133.322 Pa). Nitroglycerine decreased IVP, IMP, and AP significantly. Central coronary arterial pressure also fell significantly, but coronary venous pressures remained unchanged. In contrast dipyridamole resulted in no change in IVP, IMP, AP, or coronary arterial systolic pressures; however, the peripheral coronary venous systolic pressure became significantly elevated. Thus the two vasodilators, nitroglycerine and dipyridamole, had different effects upon coronary venous pressure. These data reinforce the recently expressed view that coronary veins behave in a complex fashion and further suggest that their pressures are dependent upon coronary artery pressure, intramyocardial pressure, and coronary venous tone.     

Suppression of high-pressure-induced hemolysis of human erythrocytes by preincubation at 49 degrees C.

When human erythrocytes were preincubated at 37-52 degrees C under atmospheric pressure before exposure to a pressure of 200 MPa at 37 degrees C, the value of hemolysis was constant (about 43%) up to 45 degrees C but became minimal at 49 degrees C. The results from anti-spectrin antibody-entrapped red ghosts, spectrin-free vesicles, and N-(1-pyrenyl)iodoacetamide-labeled ghosts suggest that the denaturation of spectrin is associated with such behavior of hemolysis at 49 degrees C. The vesicles released at 200 MPa by 49 degrees C-preincubated erythrocytes were smaller than those released by the treatment at 49 degrees C or 200 MPa alone. The size of vesicles released at 200 MPa was independent of preincubation temperature up to 45 degrees C, and the vesicles released from 49 degrees C-preincubated erythrocytes became smaller with increasing pressure up to 200 MPa. Thus, hemolysis and vesiculation under high pressure are greatly affected by the conformation of spectrin before compression. Since spectrin remains intact up to 45 degrees C, the compression of erythrocytes at 200 MPa induces structural changes of spectrin followed by the release of large vesicles and hemolysis. On the other hand, in erythrocytes that are undergoing vesiculation due to spectrin denaturation at 49 degrees C, compression produces smaller vesicles, so that the hemolysis is suppressed.     

Conformational changes preceding decapsidation of bromegrass mosaic virus under hydrostatic pressure: a small-angle neutron scattering study

The stability of bromegrass mosaic virus (BMV) and empty shells reassembled in vitro from purified BMV coat protein was investigated under hydrostatic pressure, using solution small-angle neutron scattering. This technique allowed us to monitor directly the dissociation of the particles, and to detect conformational changes preceding dissociation. Significant dissociation rates were observed only if virions swelled upon increase of pressure, and pressure effects became irreversible at very high-pressure in such conditions. At pH 5.0, in buffers containing 0.5 M NaCl and 5 mM MgCl(2), BMV remained compact (radius 12.9 nm), dissociation was limited to approximately 10 % at 200 MPa, and pressure effects were totally reversible. At pH 5.9, BMV particles were slightly swollen under normal pressure and swelling increased with pressure. The dissociation was reversible to 90 % for pressures up to 160 MPa, where its rate reached 28 %, but became totally irreversible at 200 MPa. Pressure-induced swelling and dissociation increased further at pH 7.3, but were essentially irreversible. The presence of (2)H(2)O in the buffer strongly stabilized BMV against pressure effects at pH 5.9, but not at pH 7.3. Furthermore, the reversible changes of the scattered intensity observed at pH 5.0 and 5.9 provide evidence that pressure could induce the release of coat protein subunits, or small aggregates of these subunits from the virions, and that the dissociated components reassociated again upon return to low pressure. Empty shells were stable at pH 5.0, at pressures up to 260 MPa. They became ill-shaped at high-pressure, however, and precipitated slowly after return to normal conditions, providing the first example of a pressure-induced conformational drift in an assembled system.     

Early Trends toward Class Stratification: Chaos, Common Property, and Flood Recession Agriculture

In societies based on flood recession agriculture in arid regions, economic stratification, institutionalized ways of sloughing off population, and common property are particularly valuable risk management options. Using ethnographic data from the Senegal River Basin and historical data from the Nile Valley, I argue that tendencies toward stratification were inherent in riverine societies practicing flood recession agriculture. Thus, early stratification occurred long before population pressure reached significant levels and well before regional trade, extensive storage capacity, or elaborate water-management infrastructure became economically significant. The article is intended to help explain why a number of civilizations developed in arid riverine contexts.     

Elevated intra-rumen pressure and secondary rumen contractions in sheep (Ovis aries)

1. Sheep rumens were insufflated with nitrogen to 5, 10, 15, and 20 cm water pressure and sustained at each pressure for 10 min. 2. Measurements included rumen motility, reticulorumen myoelectric activity, eructation frequency and volume, changes in tracheal pressure and rumen contraction amplitude. 3. As intra-rumen pressure increased, contractions designated as special secondary contractions appeared. 4. At a pressure of approximately 15 cm water, most of the special secondary contractions became regular secondaries; therefore, the special secondaries were called pro-secondary contractions. 5. Increased intra-rumen pressure was associated with respiratory distress. The recovery phase following, rumen insufflation was accompanied by hyperpnea.     

Propranolol-induced alterations in the pathophysiology of spontaneously hypertensive rats

Male and female, spontaneously hypertensive rats (SHR) were treated with propranolol (14 weeks) when they became 1, 4 and 8 months old prior to, during the steep ascent, and when severe high blood pressure becomes established. Propranolol prevented the usual increase in blood pressure at an early age but did not effectively lower blood pressure at all age levels. Propranolol-treated SHR manifested marked alterations in pituitary, adrenal, thymus, heart and gonadal weights. Despite progressively increasing hyperlipidemia and hyperglycemia, there were no significant differences between lipid, glucose, BUN, or serum enzyme levels in treated vs nontreated SHR. Circulating aldosterone and corticosterone levels were reduced in propranolol-treated SHR. Male SHR, treated or untreated, developed severe cardiovascular-renal lesions when they became 8 months old; none of the female SHR manifested any pathologic changes. It is suggested that the anti-hypertensive effects of propranolol were partially mediated by hormonal as well as by hemodynamic mechanisms.     

表面压与紫膜含量对紫膜LB膜质量的影响

本文报导了用表面轮廓测量仪测量了不同表面压和不同紫膜含量下制备的紫膜LB膜中紫膜碎片的厚度。实验结果表明:单个紫膜碎片在紫脂LB膜中的厚度为50左右,相当数量的紫膜碎片之间有重叠。当表面压为30mN/m或紫膜碎片与大豆磷脂之重量比为20:1时,紫膜碎片容易进入到水相或碎片之间相互重叠变得更加严重。     

Transmural pressure in the right atrium during positive pressure respiration in cats

The influence of continuous positive pressure breathing (cm H2O) on the breathing mechanics, central venous pressure, and transmural pressure in the right atrium, were studied in anaesthetised cats separately during inspiration and expiration. It's shown that hemodynamics effects are directly connected with the influence of increased intrathoracic pressure during whole breathing cycles in contrast with the phase changes in natural expiration and inspiration. The inversion of relation of intrathoracic and central venous pressure due to displacement of the mechanical respiratory characteristics became the factors defining the fall of the right atrium filling pressure.     

Studies on water vapor pressure gradient from external air through clothing to the skin in relation to external humidity and clothing conditions

Using a hygrometric capsule method developed by the authors, water vapor pressure was measured at each layer of clothing as well as at the skin surface on a human subject under actual wearing conditions. The pattern of vapor pressure gradient from the skin surface through clothing to the external air was examined in relation to the ambient vapor pressure and ths sort of textiles worn. The following findings were obtained. 1) Water vapor pressure gradient was greater between coat and external air than that between coat and underwear. The gradient became steeper again between underwear and the skin. 2) Under given clothing conditions, vapor pressure at each layer of clothing as well as at the skin varied according to the ambient humidity. However, the pattern of vapor pressure gradient from the skin through clothing to the external air was not greatly influenced by the external humidity. 3) The pattern of vapor pressure gradient from the skin through clothing to the external air was not greatly influenced by the external humidity. 3) The pattern of vapor pressure gradient through the clothing as a whole differed according to the kinds of textiles used for coat and underwear.     

Hypertension after renal transplantation.

The incidence of hypertension (mean diastolic pressure above 90 mm Hg) was evaluated in 85 patients with renal transplants whose follow-up ranged from 3 to 84 months. Bilateral nephrectomy had been performed in 80 recipients. The proportion of hypertensive subjects rose during the first three months, subsequently stabilised around 50-60% for up to five years, and then decreased slightly during the next two years. Over the years hypertension fluctuated so that one-third of the initially hypertensive patients became normotensive, and over one-third of the initially normotensive patients became hypertensive. The main single aetiological factor was renal failure. A significant relation between steroid dosage and blood pressure was found in only a quarter of the hypertensive patients, and in another quarter no cause could be found.     

Locomotor energetics and hominid evolution

The presence of a bipedal gait in fossil apes is now recognized as the earliest paleontological evidence of the beginnings of the human lineage. Thus, the search for the selective pressure that led to the adoption of bipedal posture and gait is the search for the origins of the human adaptation. One of the most popular candidates for the origin of erect posture is its purported energetic advantage.^1–4 This argument is reevaluated in light of data on the energetic cost of locomotion in mammals and, particularly, data on the effect of bipedalism on cost. I go on to discuss what morphological traces we might expect to see of changes in the locomotor economy of our ancestors once bipedalism became established.     

Alternative method for measurement of arterial pressure in the rabbit.

By using an electrical impedance plethysmorgraph and a pressure applicator to a rabbit's earlobe artery, it became possible to monitor the blood pressure for periods of several months. A study of the correlations of the blood pressure from carotid and ear was also made at varied blood pressures under different conditions which showed excellent correlations. This method could effectively replace the encannulation technique for monitoring rabbit's blood pressure in chronic experiments.     

Turgor pressure regulation and the orientation of cortical microtubules in Spirogyra cells.

Microtubules (MTs) of cells of Spirogyra sp. were depolymerized by treatment with amiprophos-methyl (APM) for 1 h and then reorganized in 0.30 M mannitol solution. The reorganized MTs after 1.5 h incubation showed an oblique/longitudinal orientation and then became transversely oriented as the incubation was prolonged. During this incubation, the osmotic pressure of cells was measured by the plasmolysis method. The cell osmotic pressure increased with time. The calculated turgor pressure at 1.5 h was 0.11 M (mannitol equivalent) and, at 13.5 h, 0.25 M. Similar changes in MT orientation and recovery of the turgor pressure were also observed in 0.30 M sorbitol solution. These results suggest that the MT orientation may be correlated with the turgor pressure. Among fresh water algae sensitive to a saline environment, this Spirogyra was the first species shown to have a turgor regulating mechanism, although the recovery of turgor pressure was incomplete. The recovery of turgor pressure in mannitol solutions was also observed without APM treatment.