Pulmonary vascular disorders in portal hypertension

The wide spectrum of pulmonary vascular disorders in liver disease and portal hypertension ranges from the hepatopulmonary syndrome characterized by intrapulmonary vascular dilatations, to pulmonary hypertension (portopulmonary hypertension), in which pulmonary vascular resistance is elevated. Since hepatopulmonary syndrome and portopulmonary hypertension have been reported in patients with nonhepatic portal hypertension, the common factor that determines their development must be portal hypertension. The clinical presentations are very different, with gas exchange impairment in the hepatopulmonary syndrome and haemodynamic failure in portopulmonary hypertension. The severity of hepatopulmonary syndrome seems to parallel the severity of liver failure, whereas no simple relationship has been identified between hepatic impairment and the severity of portopulmonary hypertension. Resolution of hepatopulmonary syndrome is common after liver transplantation, which has an uncertain effect in portopulmonary hypertension. The pathophysiology of both syndromes may involve vasoactive mediators and angiogenic factors.     

Idiopathic fibrosclerotic disorders and other inflammatory pseudotumors

Inhaled nitric oxide (iNO) is being used to treat pulmonary hypertension in a variety of chronic lung diseases associated with pulmonary vascular remodeling. We hypothesized that chronic hypoxia (CH)-induced vascular remodeling decreases the vasodilatory effectiveness of iNO due to a thickened diffusional barrier. We therefore examined segmental vasodilatory responses to iNO in U-46619-constricted lungs isolated from control and CH (4 weeks at 0.5 atm) rats using double occlusion technique. We further measured lung fluid flux and vascular wall thickness in lungs from each group to provide an index of vascular permeability and vascular remodeling, respectively. CH was associated with decreased venous, but not arterial, responsiveness to iNO in saline-perfused lungs. In addition, the presence of red blood cells (RBC) within the perfusate greatly reduced venodilation in both groups of lungs, indicating that venous responsiveness to iNO in saline-perfused lungs is largely dependent upon transport of NO from an upstream site. In contrast, RBC had no effect on arterial dilation in control lungs, but attenuated arterial dilation to iNO in lungs from CH rats. Finally, fluid flux and arterial wall thickness were greater in lungs from CH rats. We conclude that arterial remodeling associated with CH may limit venous dilation to iNO. Furthermore, the decreased arterial responsiveness to iNO following CH is consistent with extravasation of hemoglobin within the arterial vasculature.     

Significance of arterial circulation disorders for the planning of hip prosthesis interventions

Between 1980 and 1990 a total of 17 patients who had undergone or had been selected for total hip replacement were treated in the Department of Surgery at Münster University. Angiographic studies performed because of persistent symptoms revealed circulatory disorders of the pelvic floor. Vascular surgery was necessary to eliminate symptoms in these patients. Postoperative complications in 3 patients following total hip replacement were also only eliminated by vascular surgery. In the present authors' view, failure to recognize preoperatively existing arterial circulation disorders can lead to misdiagnosis and severe postoperative complications. Every hip replacement operation should be preceded by a thorough clinical and--if doubt persists--an angiological examination. Documented arterial circulation disorders should be eliminated by vascular surgery prior to hip surgery.     

Genetic study of gold-salt-induced immune disorders in the rat

BACKGROUND: Rheumatoid arthritis patients treated with gold salts occasionally develop a glomerulonephritis and an increase in serum IgE concentration. Brown-Norway (BN) rats injected with aurothiopropanolsulphonate (ATPS) exhibit an increase in serum IgE concentration, produce antilaminin antibodies (Abs) and develop glomerular linear immunoglobulin (Ig) deposits, occasionally a membranous glomerulopathy and vascular granular Ig deposits. Lewis (LEW) rats are resistant. METHODS: The genetic requirements governing the appearance of these manifestations were studied in congenic rats, and in F1 hybrids injected with ATPS. RESULTS: Non-MHC-linked genes from the BN strain were absolutely required for all the traits to be observed. The RT1n (BN) or RT1(1) (LEW) haplotypes at the MHC were permissive for all the manifestations to appear and two RT1(1) alleles were associated with the highest response. However, granular Ig deposits were only observed in RT1n rats. The high serum IgE concentration and the antilaminin Ab level were associated with the presence of glomerular Ig deposits but were not associated with the presence of vascular Ig deposits. CONCLUSIONS: This study shows that susceptibility to ATPS was mainly dependent upon non-MHC-linked BN genes and that the involvement of MHC-linked genes differed depending upon the character considered. There is an epistatic effect between the various genes.     

Editorial: Lung biopsy: how vs whom?

A method is presented for permanent catheterization of the aorta and the pulmonary artery in dogs. The preparation of single vessel catheters and double catheters for simultaneous arterial and venous sampling is described. The catheters, made of S-50-HL Tygon tubing, are introduced into the aorta and the pulmonary artery through the omocervical vessels, leaving the cerebral circulation intact. Removal of the catheter by the dog, thrombophlebitis and vascular embolism have not been observed. The catheters have remained functional for up to one year.     

Structure-activity studies of the inhibition of serine beta-lactamases by phosphonate monoesters

A new series of phosphonyl derivatives has been prepared and tested for inhibition of serine (class A and C) beta-lactamases. Variations of the leaving group in a series of methyl phosphonates showed that leaving groups better than the previously employed p-nitrophenoxide could give more effective inhibitors. Inclusion of a negative charge in the leaving group did not, per se, lead to better inhibitors. Aryl phosphonates appeared more effective than those with electronically comparable but smaller leaving groups. The combination of a good leaving group, 2,4-dinitrophenoxide, with an amido side-chain, phenylmethylsulfonamido--the latter rather than phenylacetamido in order to increase the stability of the compound with respect to intramolecular nucleophilic catalysis of hydrolysis by the amide group--did not yield overall a better inhibitor than previously employed p-nitrophenyl phosphonates. These results give the first indication of specific interactions between a beta-lactamase and the leaving group of a phosphonate inhibitor. Only one enantiomer of a chiral thiophosphonate, presumably the Rp isomer, was an effective inhibitor. Addition of either a D- or a L-methyl group to the methylene group of a p-nitrophenyl amidomethylphosphonate did not enhance the inhibitory ability of the phosphonate. Class A beta-lactamases remain refractory to phosphonates.     

Metal-substrate interactions facilitate the catalytic activity of the bacterial phosphotriesterase

The bacterial phosphotriesterase from Pseudomonas diminuta is a zinc metalloenzyme which catalyzes the hydrolysis of a variety of organophosphorus nerve agents with high efficiency. The active site of the enzyme consists of a coupled binuclear metal center embedded within a cluster of histidine residues. Potential protein-substrate interactions at the active site were probed by a systematic variation of metal identity, leaving group potential, phosphate host, and amino acid replacement. In order to determine the roles of these metal ions in binding and catalysis, the microscopic rate constants and kinetic parameters were obtained with various divalent cations. The divalent cations that were utilized in this investigation consisted of Co2+, Ni2+, Cd2+, Zn2+, Mn2+, and the mixed-metal Zn2+/Cd2+ hybrid. The leaving group potential and phosphate host were varied by altering the pKa of the departing substituted phenol or thiophenol in either a diethyl phosphate or a diethyl thiophosphate substrate. The Br?nsted plots for the nonenzymatic hydroxide catalyzed hydrolysis of these substrates showed a linear dependence between the pseudo-first-order rate constant and the pKa of the leaving group. Enzymatic activities of the wild-type enzyme with these same substrates varied by over 7 orders of magnitude over the entire experimental pKa range (4.1-10.3), and the corresponding Br?nsted plots were nonlinear. Those substrates with leaving groups with high pKa values were limited by the rate of bond cleavage while those substrates having leaving groups with low pKa values were limited by a conformational change or binding event. Thiophosphate substrates having leaving groups with high pKa values were better substrates than the corresponding phosphate analogues. These results are consistent with the direct coordination of one or both metal ions with the phosphoryl sulfur or oxygen atom of the substrate. A large dependence of the rate on the leaving group rules out the possibility of protonation of the leaving group or electrostatic interaction of the leaving group oxygen (or sulfur) with a metal ion or cationic group at the active site. The large differences in the size of the beta lg over the range of metal ions utilized by the enzyme indicate that the metal ions polarize the phosphoryl group and alter the structure of the transition state. The values of V/K(m) for the enzyme-catalyzed hydrolysis for a series of substituted thiophenol analogues were 10(2)-10(3)-fold smaller than those obtained for the hydrolysis of the corresponding phenolic substrates, suggesting that the bulkier sulfur substituent in the leaving group may induce conformational restrictions at the active site. With the zinc-substituted H201N mutant enzyme, there was a large decrease in the rate of phosphotriester hydrolysis but essentially no change in the rate of thiophosphotriester hydrolysis relative to the values observed for the zinc-substituted wild-type enzyme. These results suggest that a direct perturbation in the ligand structure of the binuclear metal center induces alterations in the mechanism of substrate hydrolysis.     

Ischemic spinal cord disorders

Infarcts in the territory of the anterior spinal artery usually are located in the Adamkiewicz artery. Onset is either sudden or progressive with clinical signs of deficit and spinal pain of short duration. The extent and distribution of the deficit depends on the extension and the level of the spinal lesions. A perfect knowledge of the spinal cord vascularization is required to discern the complex and variable clinical expression. Unlike cerebral vascular events, emboli or cardiac origin are rarely involved in spinal cord events. Aortic pathology, including surgery of the aorta, is however of major importance in ischaemic spinal cord syndromes. Several reports have shown that atheroma causing spinal cord ischaemia are not located in the perispinal arterial network but lie on the aorta and its spinal branches. Dissection of the aorta is found responsible in 2 to 8% of the cases. Isthma stenosis can also give spinal cord signs and syphylitic arteritis is exceptionally encountered. Other rare causes are gas emboli and fibrocalcium emboli.     

Comparative concentration of serum free amino acids in patients with incipient and manifest organic neuropsychiatric disorders of vascular origin

The authors conducted a study of the quantitative content of amino acids in the blood serum of patients with initial and expressed organic neuro-psychic disorders of a vascular genesis and in a group of normals of the same age. In patients with initial organic syndromes the content of cystin-cystein and treonine in the blood serum increased. In patients with expressed organic syndromes the content of cystin-cystein increased, while the content of arginine acid and leicyn-isoleicyn decreased as compared to the control group of elderly people. A comparative study of the two groups of patients with organic psychopathology of a vascular origin demonstrated that in vascular dementia there are more severe changes in the content of amino acids in the blood serum.     

Catalysis of the hydrolysis of phosphorylated pyridines by alkaline phosphatase has little or no dependence on the pKa of the leaving group

Bacterial alkaline phosphatase is an active catalyst for the hydrolysis of N-phosphorylated pyridines, with values of the second-order rate constant kcat/Km in the range 0.4-1.2 x 10(6) M-1 s-1 at pH 8.0, 25 degrees C. There is little or no dependence of the rate on the pKa of the leaving group; the value of beta 1g is 0 +/- 0.05, which may be compared with beta 1g = -1.0 for the nonenzymic reaction. Phosphorylated pyridines do not have a free electron pair available for protonation or coordination of the leaving group. Therefore, this result means that the similar, small dependence on leaving group structure for the enzyme-catalyzed hydrolysis of phosphate esters [Hall, A. D., & Williams, A. (1986) Biochemistry 25, 4784-4790) does not provide evidence for general acid catalysis or electrophilic assistance of leaving group expulsion. The results are consistent with the hypothesis that productive binding of the substrate, which may involve a conformational change, is largely rate limiting for turnover of the enzyme at low substrate concentrations.     

Triplet repeat disorders

Bosentan is a nonspecific antagonist for endothelin (ET) receptors, and BQ123 is a specific inhibitor for ET-A receptors. We compared the effects of bosentan (10 mg/kg intravenously, i.v.) and BQ123 (10 mg/kg/h i.v.) on blood pressure and renal function in deoxycorticosterone acetate (DOCA)-salt rats, Dahl salt-sensitive (Dahl-S) rats, and normotensive Wistar rats. In normotensive Wistar rats, bosentan and BQ123 decreased blood pressure. Only BQ123 decreased glomerular filtration rate (GFR) and filtration fraction. These results indicate that ET-A receptors play a role in glomerular function. In DOCA-salt rats, bosentan and BQ123 caused a decrease in blood pressure to normal range and a decrease in renal vascular resistances. Bosentan decreased filtration fraction. Paradoxically, BQ123 caused a decrease in GFR. In Dahl-S rats, bosentan and BQ123 decreased blood pressure, but blood pressure did not reach normal ranges. Bosentan did not modify renal function, but BQ123 caused a decrease in the GFR and filtration fraction. Our results confirm the importance of specific and nonspecific ET antagonists in decreasing blood pressure in models of salt-dependent hypertension. However nonspecific inhibition of ET action did not improve renal function and specific inhibition of ET-A receptors by BQ123 temporarily worsened renal function.     

Risk factors for substance use disorders among inpatients with major affective disorders in Taiwan Chinese

The explanation by differential diagnosis of pathological changes of the fundus may be particularly difficult in case of diseases of sporadic occurrence. The examination findings in a 19-year-old patient with a choroidal osteoma are presented. Large arciform, atrophic areas with distinct boundaries and star-shaped vascular structures were dominant in the fundus on both sides. With peripapillar manifestation, the optic nerve head was ophthalmoscopically noncontributory. A submacular bleeding had caused sudden reduction of visual acuity and caused the patient to visit the ophthalmologist. The most important diagnostic key was supplied by echography, which established peripapillar scleral calcification. The posterior eye segment was highly reflective in ultrasonic echography (B mode), showing concave deformation and causing the sound shadow. Visually evoked potentials indicated the onset of the compression of the optic nerve by the choroidal osteoma. Diagnostic and treatment possibilities are discussed.     

Production and absorption of nitric oxide gas in the nose

Some nitric oxide gas (NO) produced in the sinuses and nasal cavity is absorbed before leaving the nose. To measure production and absorption, we introduced NO at different concentrations into one nostril while sampling the NO leaving the opposite nostril with the soft palate closed. The quantity of NO gas produced in six normal subjects (amount leaving plus the amount absorbed) averaged 352 nl/min and was the same at gas flows ranging from 8 to 347 ml/min and at 10 l/min. An absorption coefficient A was calculated by dividing the amount of NO absorbed by the concentration leaving the nose. A ranged from 17 ml/min at a nasal gas flow of 8 ml/min to an A of 24 ml/min at a nasal gas flow of 347 ml/min. The calculated rates of production and absorption did not change when gas flow rate was increased, suggesting diffusion equilibrium. The amount of uptake of NO in the nasal mucosa can be explained by its solubility coupled with tissue and blood reactivity.     

Putative role of adhesion molecules in metabolic disorders

Diabetes mellitus is associated with an increased risk of premature vascular disease. Vascular research is focusing on a potential role of adhesion molecules in diabetes mellitus, since classical risk factors including hyperlipidemia and hypertension do not completely account for the increased incidence of atherosclerosis in diabetes. After the expression of adhesion molecules on the cell surface, they are shed into plasma. Thus plasma concentrations of circulating adhesion molecules may be representative for endothelial activation, damage or turnover. Recently, evidence has been accumulating that increased plasma levels of adhesion molecules may predict cardiovascular disease, may be pathognomonic for diabetic microangiopathy or may even play a functional pathophysiologic role. The purpose of this article is to briefly summarise the role of (circulating) adhesion molecules in diabetes mellitus.     

Conceptual approaches to the diagnosis of stress-induced functional disorders in humans under conditions of industrial activity

In accordance with the fundamental concept of the systems symmetrical approach, a model of the body's "ideal functional status" and a polyparametric method for diagnosing the human functional status (the method has been patented in Russia) were developed, on the basis of the unified set of amplitude and time parameters of a complex of physiological parameters (ECG, etc.). The systems symmetrical approach is basically new in defining the ratio of harmonic parameters acting as new diagnostic evidence for the health status. The unchanging ratio of parameters of autovariation processes in the cardiac, vascular, and respiratory systems, their changes in the development of the adaptative syndrome and the value were examined in healthy individuals at rest and during exercise an intensive productive activity (point brazing at a plant of electron devices), and in the trainees. It was demonstrated that the mechanism of development of adaptative processes was associated with the synchronization of autovariations in the cardiorespiratory and vascular systems and the involution of adaptative processes, their break, depletion, i.e. stress, were determined by the imbalance of relationships and the desynchronization of autovariations in these systems. To define a set of cardiorespiratory and hemodynamic parameters is necessary, but insufficient to evaluate (diagnose) the health status and health-disease intermediate diseases (stress and adaptative overtension). The ratio harmonicity of these parameters, i.e. well-balanced relations between the subsystems is the main characteristic. The assessment of the human health status in terms of the reference-the model of the ideal status as the ideal health status without using the complex and indefinite concept of the normal and moderate health status-is conceptual for polyparametric status estimation.     

Rorschach indicators of dissociative identity disorders: clinical utility and theoretical implications

A series of 1,4-dihydropyridines bearing a coumarin moiety in 4-position was synthesized. The compounds were evaluated for inotropic, chronotropic and calcium antagonist activities. The replacement of the o-nitrophenyl moiety of nifedipine with a coumarin or phenylcoumarin system is accompanied by a decrease of the activity on myocardial and vascular parameters, but the synthesized compounds showed selective inhibiting effects on cardiac contractility and frequency.     

Adolescent outcomes of childhood disorders: the consequences of severity and impairment

The clinical use of positron emission tomography (PET) is expanding rapidly in most European countries. It is likely therefore that patients receiving the tracer fluorine-18 fluorodeoxyglucose (18FDG) will be discharged to come into contact with family members, members of the public and ward staff. There are few direct measurements on which to base any recommendations with regard to radiation protection, and so we have measured the dose rates from patients undergoing clinical PET examinations in our centre. Seventy-five patients who underwent whole-body and brain 18FDG PET examinations were studied. Dose rates were measured at 0.1, 0.5, 1.0 and 2.0 m from the mid thorax on leaving the department. The median administered activity was 323 MBq with a 95th percentile value of 360 MBq. The median dose rates measured at the four distances were 90.0, 35.0, 14.0 and 5.0 microSv h-1 (the median dose rates per unit administered activity at 2 h post injection were 0.31, 0.11, 0.04 and 0.02 microSv h-1 MBq-1). The corresponding 95th percentile values were 174.0, 69.0, 29.0 and 7.5 microSv h-1 (0.43, 0.2, 0.08 and 0.03 microSv h-1 MBq-1). A number of social situations were modelled and an annual dose limit of 1 mSv was used to determine whether restrictive behavioural advice was required. In the case of nursing staff on wards a value of 6 mSv was regarded as the annual limit, which translates to a daily limit of approximately 24 microSv. There is no need for restrictive advice for patients travelling by public or private transport when they leave the department 2 h after the administration of 18FDG. Similarly, there is no need for restrictive advice with regard to their contact with partners, work colleagues or children of any age, although it should be stressed that children should not accompany the patient to the scanning department. The only possible area of concern is in an oncology ward, where patients may be regularly referred for PET investigations and other high activity radionuclide studies and are partially helpless. Even in this area, however, it is unlikely that a nurse would receive a daily dose of more than 24 microSv. We conclude that there is no need for restrictive advice for patients undergoing 18FDG PET studies given the current administered activities.     

Homeostatic reconditioning in stress-related disorders: A preliminary study of migraine headaches.

18 19–55 yr old migraine headache patients were assigned to a group that learned (1) to raise finger temperature, via visual biofeedback, after neutral imaginal experiences or (2) to raise finger temperature after stressful imaginal experiences. At the completion of training, Ss participated in an outcome session without feedback. Laboratory training, combined with home practice using the same respective imaginal experiences, resulted in Ss' being able, with on-task concentration, to raise finger temperature without feedback and also resulted in significant clinical reductions in headache activity. Improvement was more marked at 4-wk follow-up. Ss trained in vascular recovery after stress showed more improvement than did other Ss. Overall, the Ss who showed the most reliable vascular recovery conditioning effects were those whose migraine prodromal symptomatology was not an accurate predictor of headache or absence of headache. The significance of what is called homeostatic reconditioning, after stress, in stress-related disorders, rather than the "aspirin" approach of many biofeedback treatments, is discussed. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Transition section in continuous bar casting during the serial casting of different steels

In continuous slab casting at OAO Magnitogorskii Metallurgicheskii Kombinat (MMK), metal of different grades in a series is separated by leaving an appropriate quantity of steel from the previous melt in the intermediate ladle. The losses of metal are least on leaving around 12 t of steel in the intermediate ladle. The mass of the transition sections of mixed composition in the bar billet is 2.5 times the mass of the steel left in the ladle.