Changes in cerebral receptors for gamma aminobutyric acid in patients with hepatic encephalopathy

If the gamma-aminobutyric acid (GABA) inhibitory neurotransmitter system plays an important role in the mediation of hepatic encephalopathy (HE) in man, changes in the status of receptors for GABA in the brain may occur in patients with HE. To test this possibility, brains were obtained at autopsy from 11 patients who had died of causes unrelated to liver disease and from 11 patients who had died with chronic liver disease. Eight of the liver disease group had overt HE at the time of death. The specific binding of GABA to synaptic membranes isolated from frontal cortex was determined. Mean specific binding of GABA for patients with cirrhosis without overt HE was similar to that for control patients. In contrast, corresponding means for patients who had mild HE (stages I-III) and for patients who had severe HE (stage IV) were 45% higher (p less than 0.05) and 43% lower, respectively, than that for control patients. The mean specific binding of GABA was significantly greater for patients with mild HE than in patients with severe HE (p less than 0.025). Scatchard plots of the GABA binding data were curvilinear and consistent with a model of GABA receptors with two independent binding sites. Computer-assisted analysis of the binding data indicated that the altered GABA binding observed in patients with HE is attributable to changes in the affinity rather than the density of both GABA receptors (increased affinities in mild HE, and decreased affinities in hepatic coma). These findings are compatible with the hypothesis that alterations in GABAergic neurotransmission are associated with and contribute to the syndrome of HE in man.     

Corticosteroids repress the interleukin 1 beta-induced secretion of collagenase in human intestinal smooth muscle cells

BACKGROUND & AIMS: The cytokine interleukin (IL)-1 beta induces collagenase expression and inhibits collagen expression in human intestinal smooth muscle (HISM) cells. Corticosteroids cause transrepression of certain genes, including the collagenase gene. The aim of this study was to determine if corticosteroids repress the induction of collagenase expression and the inhibition of collagen secretion by IL-1 beta in HISM cells. METHODS: HISM cells were exposed to IL-1 beta (1-100 pmol/L) for 24 hours in the presence or absence of dexamethasone (10(-6) mol/L). Collagenase messenger RNA (mRNA) levels were determined by ribonuclease protection assay. Collagenase and tissue inhibitor of metalloproteinase protein secretion were determined by enzyme-linked immunosorbent assay of culture medium. Procollagen and collagen secretion were determined by polyacrylamide slab gel analysis of radiolabeled proteins in culture medium. RESULTS: A 30-fold induction of collagenase mRNA and collagenase protein secretion by IL-1 beta was completely abrogated by dexamethasone. Dexamethasone at 10(-6) mol/L also reduced basal levels of collagenase mRNA by 50% and blocked the IL-1 beta-induced inhibition of collagen secretion. CONCLUSIONS: Corticosteroids repress the collagenolytic action of IL-1 beta on HISM cells in vitro and therefore should promote healing in the inflamed intestine. (Gastroenterology 1997 Dec;113(6):1924-9)     

依那普利致急性心肌梗死后心绞痛发作二例

依那普利致急性心肌梗死后心绞痛发作二例贾勤惠翟秀军邸亚新陈瑞英例１男性，６８岁，维族。因间断心前区疼痛１０小时于１９９６年１月３０日入院。１９８２年患急性下壁心肌梗死，无高血压及糖尿病史。入院后第６天凌晨３时，突然心前区剧烈疼痛，大汗。心电图示Ｖ１～...     

Effects of SSRI medication on heart rate and blood pressure in individuals with hypertension and depression

Objective: To test the role of escitalopram on blood pressure and heart rate of individuals with hypertension and depression.

Methods: A total of 30 individuals participated in this study who were being treated for hypertension and were diagnosed with major depression. Escitalopram (10–20 mg) was administered to 15 individuals, while the other 15 received placebo. These individuals were followed for 8 weeks with regular monitoring of blood pressure and heart rate. Scores on the Hamilton Depression Rating Scale were evaluated within the first, second, fourth, and eighth weeks of the study onset.

Results: Comparing with placebo, heart rate was lower in the escitalopram group (66.79 ± 9.85 vs. 74.10 ± 9.52 bpm, p = 0.044). There was not a significant decrease of systolic blood pressure (140.80 ± 16.48 vs 139.61 ± 18.92 mmHg, p = 0.85) and diastolic blood pressure (80.55 ± 12.64 vs 80.18 ± 16.36 mmHg, p = 0.94).

Conclusion: Escitalopram decreases HR, but not BP, in individuals with hypertension and depression.

Abbreviation: SH: systemic hypertension; BP: blood pressure; DSM: Diagnostic and Statistical Manual of Mental Disorders; SRQ 20: Self-Report Questionnaire; SCID: Structured Clinical Interview for DSM-IV; HR: heart rate; SNS: Sympathetic nervous system; HPA: hypothalamus-pituitary-adrenal axis; RAA: renin, angiotensin, aldosterone system; NE: norepinephrine; CSF: cerebrospinal fluid; HAM-D: Hamilton Depression Rating Scale; CRF: corticotropin releasing factor; ACTH: adrenocorticotropic hormone; BMI: Body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; t: time.     

Sequence homologies between A subunits of Escherichia coli and Vibrio cholerae enterotoxins.

The genes coding for the heat-labile enterotoxin LT produced by Escherichia coli have been cloned into the plasmid pBR313. Using DNA derived from the resulting chimeric plasmid, we determined the nucleotide sequence of two regions of the gene coding for the enzymatically active A subunit of LT. Translation of the nucleotide sequence gives the primary structure of the NH2-terminal and COOH-terminal regions of the LT A subunit. This permits direct comparison of the LT A subunit with the A subunit of cholera toxin. Our results show that the two toxins possess homologous sequences, of varying degrees, in both regions of their primary structure. The order of the component A1 and A2 polypeptides is A1-A2. The nucleotide sequence predicts the existence of a signal sequence of 18 amino acids at the NH2-terminus of the A subunit.     

Calin from Hirudo medicinalis, an inhibitor of von Willebrand factor binding to collagen under static and flow conditions

Calin from the saliva of the medicinal leech, Hirudo medicinalis, is a potent inhibitor of collagen mediated platelet adhesion and activation. In addition to inhibition of the direct platelet-collagen interaction, we presently demonstrate that binding of von Willebrand to coated collagen can be prevented by Calin, both under static and flow conditions in agreement with the occurrence of binding of Calin to collagen, confirmed by Biospecific Interaction Analysis. To define whether Calin acted by inhibiting the platelet-collagen or the platelet- von Willebrand factor (vWF)-collagen-mediated thrombus formation, platelet adhesion to different types of collagens was studied in a parallel-plate flow chamber perfused with whole blood at different shear rates. Calin dose-dependently prevented platelet adhesion to the different collagens tested both at high- and low-shear stress. The concentration of Calin needed to cause 50% inhibition of platelet adhesion at high-shear stress was some fivefold lower than that needed for inhibition of vWF-binding under similar conditions, implying that at high-shear stress, the effect of Calin on the direct platelet- collagen interactions, suffices to prevent thrombus formation. Platelet adhesion to extracellular matrix (ECM) of cultured human umbilical vein endothelial cells was only partially prevented by Calin, and even less so at a high-shear rather than a low-shear rate, whereas the platelet binding to coated vWF and fibrinogen were minimally affected at both shear rates. Thus, Calin interferes with both the direct platelet- collagen interaction and the vWF-collagen binding. Both effects may contribute to the inhibition of platelet adhesion in flowing conditions, although the former seems to predominate.     

Cognitive Performance of Alcoholics: A Longitudinal Evaluation of the Role of Drinking History, Depression, Liver Function, Nutrition, and Family History

To assess the role of drinking history, depression, liver function, nutrition, and family history on cognitive performance, 171 detoxified male alcoholics were administered a brief neuropsychological examination at admission and discharge from an inpatient treatment program and at a 3-month follow-up evaluation. Regression analyses showed that at admission, depression and liver function were significant predictors of neuropsychological performance, whereas at discharge 3 to 4 weeks later only age and an estimate of premorbid intelligence were significant predictors. At the 3-month follow-up, estimates of drinking following discharge and severity of depressive symptoms were major significant predictors of neuropsychological performance. Indices of drinking prior to admission to the treatment program, nutrition, and family history for alcoholism did not predict performance on any of the three test occasions. These findings indicate that in addition to the chronic neurotoxic effect of alcohol a number of different medical and psychiatric factors, as well as the acute effects of alcohol, contribute to the cognitive scores of patients at various points in the clinical course.     

The hypercoagulable states

Patients are considered to have hypercoagulable states if they have laboratory abnormalities or clinical conditions that are associated with an increased risk of thrombosis (prethrombotic states) or if they have recurrent thrombosis without recognizable predisposing factors (thrombosis-prone). The number of specific primary hypercoagulable states that are recognized is growing. These disorders are generally inherited abnormalities of coagulation in which a physiologic anticoagulant mechanism is defective: for example, antithrombin III deficiency, protein C and protein S deficiency, abnormalities of the fibrinolytic system, and dysfibrinogenemias. Secondary hypercoagulable states are generally acquired disorders in patients with underlying systemic diseases or clinical conditions known to be associated with an increased risk of thrombosis: for example, malignancy, pregnancy, use of oral contraceptives, myeloproliferative disorders, hyperlipidemia, diabetes mellitus, and abnormalities of blood vessels and rheology. The complex pathophysiologic features of these secondary hypercoagulable states are discussed, and a framework is provided for the laboratory investigation and systematic clinical approach to the patient.     

A Comparison of 4D DSA with 2D and 3D DSA in the Analysis of Normal Vascular Structures in a Canine Model

BACKGROUND AND PURPOSE:4D DSA allows viewing of 3D DSA as a series of time-resolved volumes of a contrast bolus. There is no comparison of the accuracy of the anatomic information provided by 4D DSA with that available from conventional 2D and 3D DSA. Our purpose was to make this comparison by using a canine model.MATERIALS AND METHODS:2D, 3D, and 4D DSA acquisitions were performed in 5 canines from 3 catheter positions in the common carotid artery yielding 15 2D, 15 3D, and 15 4D datasets. For each territory, 3 vascular segments were chosen for comparison. Images were reviewed by 2 experienced neuroradiologists and were graded by the ability to visualize a segment, its filling direction, and preferred technique. Two visualization modes for 4D DSA were compared (volume-rendering technique and MIP).RESULTS:4D DSA was preferred in 73.9% of the image sets; 2D, in 22.7%; and 3D, in 3.4%. 4D DSA MIP rendering yielded superior visualization of very small vessel details; the 4D DSA volume-rendering technique offered superior depth and overlap information and better visualization of the surface details of the vasculature.CONCLUSIONS:In this study, 4D DSA was preferred over 2D and 3D DSA for analysis of normal vasculature. The ability to provide any view of a vascular territory at any time during passage of a contrast bolus seems likely to reduce the need for many 2D acquisitions during diagnostic and therapeutic procedures. This then potentially translates into a reduction in radiation and contrast dose.

4D DSA provides the ability to create a series of time-resolved volumes of vasculature so that the passage of a contrast bolus may be viewed in 3D at any time and from any angle. Traditional 3D DSA acquisitions provide volumetric anatomic information but are not time-resolved. The overlap of vasculature in these 3D images often makes it difficult to analyze details (eg, angioarchitecture of an AVM nidus). To overcome this problem, multiple 2D DSA acquisitions at different angles are often necessary. The 4D algorithm applied to data from a rotational acquisition, obtained by using an injection protocol that starts the injection shortly after rotation of the C-arm rather than simultaneous with its rotation, results in a series of 4D DSA volumes that provides a user with the ability to view both anatomic information and contrast dynamics.¹ The anatomic information provided by this technique has not, to our knowledge, been compared with that provided by conventional 2D and 3D DSA images. In this study, we aimed to assess the ability of 4D DSA to depict vascular anatomy. Our methods also aimed to acquire data that would allow us to make judgments as to whether the content was superior to and/or complementary to that of conventional DSA studies. We believed that this comparison was important because the ability to view relevant vasculature at any time and at any angle with a 4D reconstruction should result in less need to acquire multiple 2D series in both diagnostic and interventional procedures, thereby leading to reductions in both x-ray and contrast medium doses.     

The effect of antidiuretic hormone on solute flows in mammalian collecting tubules

These experiments were intended to evaluate the antidiuretic hormone (ADH)-dependent reflection coefficients of urea, sucrose, and NaCl in cortical and outer medullary collecting tubules isolated from mammalian kidney. In one group of experiments, the ADH-dependent osmotic water flows, when the perfusing solutions contained hypotonic NaCl solutions, were indistinguishable from control observations when either urea or sucrose replaced, in part, NaCl in isotonic bathing solutions (cortical collecting tubules). Similarly, both in cortical and outer medullary collecting tubules exposed to ADH, there was zero net osmotic volume flow when a portion of the NaCl in the bathing and/or perfusing solutions was replaced by either sucrose or urea, so long as the perfusing and bathing solutions were isosmolal. Taken together, these observations suggest that the ADH-dependent reflection coefficients of NaCl, urea, and sucrose, in these tubules, were identical. Since the effective hydrodynamic radii of urea and sucrose are, respectively, 1.8 and 5.2 A, it is likely that sigma(i), for urea, sucrose, and NaCl, was unity. In support of this, the diffusion permeability coefficient (P(Di) cm sec(-1)) of urea was indistinguishable from zero. Since the limiting sites for urea penetration were the luminal interfaces of the tubules, these data are consistent with the view that ADH increases diffusional water flow across such interfaces.