Ecotypic differences in responses of Arabidopsis thaliana L. to elevated polychromatic UV-A and UV-B+A radiation in the natural environment: a positive correlation between UV-B+A inhibition and growth rate.

The effects of supplementary ultraviolet-A (UV-A) and ultraviolet-B+A (UV-B+A) in the natural environment on the growth and morphology of various ecotypes of Arabidopsis thaliana were investigated. The ecotypes investigated were Columbia (Col-4), Landsberg erecta (Ler-0), Cvi-0, Wassilewskija, Enkheim-D, Aa-0 and Di-1. The mutant hy-4 was also used. Results varied with the radiation treatment, ecotype and parameter measured. Plants subjected to elevated UV-A were both insensitive (all parameters Cvi-0 and Col-4) and sensitive. When responses to UV-A occurred they were mostly inhibitory (all significant responses of Di-1 and Enkheim-D, most parameters of Wassilewskija, and some parameters of hy-4), however, promotive affects were observed for some parameters of Aa-0 and Ler-0. Supplementary UV-B+A inhibited all parameters of Di-1 and Enkheim-D and most parameters of Col-4, Ler-0 and hy-4, but Wassilewskija, Aa-0 and Cvi-0 were mostly insensitive. The magnitude of the UV-B+A response varied with ecotype (compare Di-1 with Ler-0). Some ecotypes were sensitive to UV-A but not UV-B+A (Aa-0), whereas others (Ler-0, Col-4) show the opposite sensitivities. A linear relationship is reported between the degree of UV-B+A inhibition of each ecotype and growth rate. The higher the growth rate the more susceptible the ecotype is to UV-B+A inhibition. This relationship holds for the majority of growth parameters measured.

Interaction of biofeedback-assisted relaxation and diuretic in treatment of essential hypertension.

Thirty patients with essential hypertension participated in a study designed to compare two treatments: diuretic medication alone (n = 10) and biofeedback assisted relaxation combined with diuretic (n = 20). One of 10 patients lowered BP with diuretic alone and 11 of 20 patients lowered BP with diuretic combined with biofeedback-assisted relaxation. The addition of the behavioral intervention to the diuretic therapy produced a decrease in blood pressure beyond that associated with the diuretic alone. The decrease in BP mediated by diuretic were related to high entry levels of BP, low anxiety, forehead muscle tension, anger expression and plasma renin activity. The BP decrease mediated by combined diuretic and biofeedback-assisted relaxation was associated with high pretreatment BP, anger controlled, low finger temperature and high/normal plasma renin activity.

Effect of repeated measurements of blood pressure on blood pressure in essential hypertension: role of anxiety.

Over the past years, we repeatedly observed that of the hypertensive population entered into our behavioral treatment programs, more than half were actually false hypertensives. With repeated measurements of blood pressure (BP), only one-third remained hypertensive, while two-thirds showed a significant decrease in BP. The purpose of this study was to determine which factors correlate with the decrease in BP and could be useful in distinguishing the true and the false hypertensives. Of the 24 patients in this study, 15 decreased their mean arterial pressure by at least 5 mm Hg during a 6-week period of home and clinic BP measurement, while 9 did not. The 9 patients with BPs that did not change had lower State Anxiety, Trait Anxiety scores, lower diastolic BP, and lower heart rates compared to the group whose BPs decreased. These results suggest that under certain conditions a relationship exists between anxiety and elevated blood pressure. In a segment of the hypertensive population, anxious patients may be placed on inappropriate antihypertensive medication if a BP measurement period is not conducted before intervention.

Norepinephrine stimulation of sodium transport in Necturus urinary bladder.

Norepinephrine alters the transepithelial electrical properties of an open-circuited urinary bladder from the mud puppy, Necturus maculosus. When 10(-5) M norepinephrine is superfused over the serosa of the epithelium, the transepithelial voltage (Vt) and short-circuit current (Isc) increase as the resistance (Rt) decreases. The norepinephrine-mediated changes are reversed by the addition of amiloride (5.10(-5) M) to the mucosal Ringer's solution. The serosal adrenoceptors mediating the Na+ transport are more sensitive to norepinephrine (EC50 = 1.2.10(-6) M) than to epinephrine or isoproterenol. Since the Isc is blocked selectively by the antagonist, phenoxybenzamine, stimulation of active transepithelial Na(+)-flux by catecholamines is mediated by an alpha-adrenoceptor. The apical cell membrane voltage (Va) and fractional resistance (fRa) were recorded using conventional KCl-filled microelectrodes. Untreated tissues have Va close to 0 mV while the basolateral membrane voltage (Vb) is between -85 and -95 mV. About 90% of Rt is apical cell membrane resistance (fRa). When amiloride inhibits sodium transport, Va becomes negative, Vb hyperpolarizes slightly and fRa increases to 97%. On the other hand, if the bladders are treated with norepinephrine, fRa decreases to 79% as Va becomes positive and Vb depolarizes. When Rt changes, the resistance of the paracellular pathway (Rp) is unaltered. Changes in the electrical properties of the tissue appear to be mediated primarily by alterations in Ra. Since the Necturus bladder does not respond to antidiuretic hormone, this study implies that biogenic amines regulate Na+ transport in the epithelium.

Prediction of response to biofeedback-assisted relaxation in hypertensives: development of a Hypertensive Predictor Profile (HYPP).

A group of hypertensive patients who participated in a biofeedback-assisted relaxation program were divided into treatment successes and treatment failures based on the change in their blood pressure. Multiple regression analysis was used to characterize the successes and failures and to develop a hypertensive predictor profile. Hypertensives most likely to lower their blood pressure with biofeedback-assisted relaxation are those in whom there is evidence of autonomic overactivity, for example, cool hands, high heart rates, and evidence of a chronic response to stress, such as high anxiety scores and high normal cortisol levels.

Accuracy of two equations in determining normalized phenytoin concentrations.

The accuracy of two equations in normalizing total phenytoin concentrations in the presence of renal failure or hypoalbuminemia was evaluated in 11 renal failure and 23 hypoalbuminemic patients. Blood samples were obtained from hospitalized patients receiving phenytoin and were assayed for free and total phenytoin concentrations. Estimated normalized phenytoin concentrations based on free drug concentration were compared statistically with normalized concentrations calculated from the two equations via Student's t-test. The equation for normalizing phenytoin concentrations in hypoalbuminemic patients significantly underpredicted normalized phenytoin concentrations 15.7 +/- 8.5 versus 19.9 +/- 12.1 mg/L (p less than 0.001). In patients with renal failure, the mean phenytoin concentration from the respective equations and that based on free concentration were 14.1 +/- 6.2 and 14.0 +/- 7.9 mg/L, respectively. However, in 5 of 11 renal failure patients the equation resulted in over- or underprediction by at least 25 percent. Neither equation should be used clinically to normalize phenytoin concentrations in these patient populations.

Catecholamine stimulation of ion transport in the toad urinary bladder.

We have observed that serosal catecholamines increase the amplitude of the short-circuit current (Isc) in the toad urinary bladder by as much as 450%. Chemical sympathectomy with 10(-6) M 6-hydroxydopamine and the sympathomimetic effects of 10(-5) M tyramine indicate a reservoir of amines in the serosal stroma of the tissue. The urinary epithelium from the toad responds to six adrenoceptor agonists: (-)-epinephrine, (-)-norepinephrine, (-)-phenylephrine, clonidine, methoxamine and oxymetazoline. The alpha 2-adrenoceptor agonist clonidine is most potent for stimulating Isc. Some agonists were found to diminish Isc. Apparently this is related to a simultaneous increase in the transepithelial flux of both chloride and sodium. The Isc response to the catecholamines is also inhibited by several adrenoceptor antagonists. The alpha 2-adrenoceptor antagonist yohimbine is more effective than the alpha 1-antagonist prazosin for blocking the stimulation of epithelial transport. As a result of these studies, we have tentatively classified the serosal adrenoceptor of the toad urinary bladder as alpha 2.

Pharmacokinetics of imipenem-cilastatin in patients with renal insufficiency undergoing continuous ambulatory peritoneal dialysis.

In six patients with end-stage renal disease, a single bolus of imipenem-cilastatin (500 mg each) was given either intravenously or intraperitoneally in a randomized crossover protocol such that each patient received the drug by both routes at a 2- to 3-week interval. Drug levels in plasma and the peritoneal dialysis fluid were analyzed at frequent intervals, and various pharmacokinetic variables were calculated for a one-compartment open model. Data obtained in the present study suggest that while no significant difference in peak plasma levels or volume of distribution were noted, the following variables were significantly different for imipenem as compared with cilastatin: elimination half-life, total plasma clearance, area under the concentration-time curve, and percent drug excretion in the peritoneal dialysis fluid. The elimination half-life of imipenem (3.28 h) or cilastatin (8.84 h) in our patients was in the same range as observed in patients with minimal renal function undergoing hemodialysis. The dose of imipenem-cilastatin should be reduced appropriately in patients with end-stage renal disease undergoing peritoneal dialysis.

Response of toad urinary bladder to vasopressin analogs possessing V1 or V2 specificity.

The urinary bladder of the toad Bufo marinus has been used to examine the effect on sodium transport, measured by short-circuit current, of natural antidiuretic hormones and several synthetic peptide analogs. In mammals, these synthetic analogs show specificity for different receptors, designated V1 and V2 receptors, whose biological responses are mediated by phosphatidyl inositol breakdown products or adenylate cyclase activity, respectively. All analogs stimulated SCC, with relative potencies AVT greater than AVP greater than Phe2 OVT (V1 agonist) much greater than d(CH2)5Tyr(Me)AVP (V1 antagonist) = d(CH2)5[D-Ile2,Abu4]AVP (V2 antagonist). The V1 and V2 antagonists inhibited the SCC response to AVT and Phe2OVT, with similar inhibitory potencies. We conclude that the stimulation of sodium transport by antidiuretic hormones involves one hormone receptor which does not show the selectivity of mammalian antidiuretic hormone receptors, and may represent a more primitive type of receptor.

Antihypertensive effectiveness of the nifedipine gastrointestinal therapeutic system.

The results of a multicenter trial conducted in order to determine the therapeutic efficacy of the gastrointestinal therapeutic system (GITS) formulation of nifedipine in comparison with hydrochlorothiazide and placebo in the management of mild to moderate essential hypertension are presented. During a one-week wash-out phase, antihypertensive therapy was discontinued in all patients. After a three-week single-blind placebo period, eligible patients were randomly assigned in a double-blind fashion to one of three treatment groups for a one-week titration period and a nine-week efficacy period. Patients received either nifedipine GITS, 30 or 60 mg daily; hydrochlorothiazide, 25 or 50 mg daily; or placebo. Sitting and standing blood pressures decreased by an average 11.6/10.4 and 10.8/10.8 mm Hg, respectively, with nifedipine GITS therapy, and 14.8/10.8 and 14.3/8.2 mm Hg, respectively, with hydrochlorothiazide therapy. Compared with placebo, these changes were highly significant for both sitting (p less than or equal to 0.005) and standing (p less than or equal to 0.02) measurements. Heart rate remained essentially unchanged in all three groups. It was therefore concluded that monotherapy with nifedipine GITS, at doses of 30 or 60 mg given once daily, effectively reduces blood pressure in patients with hypertension to a degree comparable with that seen in hydrochlorothiazide therapy.

Effect of biofeedback-assisted relaxation on blood pressure and cortisol levels in normotensives and hypertensives.

This report examines the relationship between blood pressure and cortisol in normotensives and hypertensives. Both groups received biofeedback-assisted relaxation training. Both groups significantly decreased their muscle tension levels from baseline. Only the hypertensives decreased their blood pressure and cortisol levels after training. Implications for the role of cortisol in the relaxation response and in hypertension are discussed.

Predictors of success in hypertensives treated with biofeedback-assisted relaxation.

This paper describes differences in response in seventeen patients with essential hypertension who participated in a treatment program consisting of electromyograph biofeedback assisted relaxation training. Responders were found to have higher treatment values of urinary and plasma cortisol, Trait Anxiety and forehead muscle tension compared to treatment failures. Responders also sustained greater decreases in plasma, and urinary cortisol after treatment. These data are discussed in light of the ability to predict which hypertensive patients may be most benefitted by a relaxation based treatment.

Ceftizoxime elimination kinetics in continuous ambulatory peritoneal dialysis.

We investigated the kinetics of ceftizoxime, a beta-lactamase stable cephalosporin, in eight subjects undergoing continuous ambulatory peritoneal dialysis (CAPD). A single 500-mg or 1-gm dose was injected IV, or a 500-mg dose was given intraperitoneally in the CAPD fluid during a 6-hr dwell time. The ceftizoxime (500 mg) serum kinetic parameters were as follows: peak concentrations, 21 to 46 mg/l; volume of distribution, 0.27 l/kg; elimination rate constant, 0.0784 hr-1; plasma clearance, 1.66 l/kg hr-1; and t1/2, 10.2 hr. The t1/2 after 1 gm was 12 hr. Dialysate ceftizoxime concentrations rose rapidly between 0.25 and 2 hr and slowly over the next 4 hr, but only 4.04 +/- 1.8 and 7.4 +/- 2.9 mg ceftizoxime/hr was eliminated by the peritoneal route over a 6-hr dwell time after 500 mg or 1 gm IV. This represents only 4% to 5% of the dose. After intraperitoneal instillation, the antibiotic appeared in the serum within 15 min in all four subjects, and the peak serum concentrations ranged from 12 to 19.8 mg/l (mean +/- SD = 16.4 +/- 3.3) between 5 and 6 hr. Approximately 78% of ceftizoxime was absorbed from the peritoneal dialysis fluid during a single 6-hr dwell time. Rate constant for absorption, ka, was 0.3959 hr-1 and absorption t1/2 was 1.75 hr (as calculated by the residual equation). These data suggest that ceftizoxime has bidirectional exchange characteristics through the peritoneal membrane. Instillation of ceftizoxime in CAPD fluid alone may permit rapid absorption to reach therapeutic serum concentrations.

Amiloride stimulation of sodium transport in the presence of calcium and a divalent cation chelator.

Amiloride in nM to microM concentrations stimulates the short circuit current (Isc) of the toad urinary bladder by as much as 120% when applied in conjunction with apical Ca2+ and a divalent cation chelator. A significant decrease in transepithelial resistance (Rt) is observed simultaneously. This response is spontaneously reversible and its amplitude is dependent upon apical sodium concentrations. The stimulated Isc persisted when acetazolamide (1 mM) was introduced, HPO2-4 substituted for HCO-3 or SO2-4 replaced Cl-. Consequently, the increase in Isc is not due to the change of Cl-, H+ or HCO-3 flux. This behavior in a 'tight' epithelium may be related to the mechanism controlling apical sodium permeability.

Unidirectional absorption of gentamicin from the peritoneum during continuous ambulatory peritoneal dialysis.

Gentamicin kinetics were determined after intravenous or intraperitoneal injection in five patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Our objective was to determine rate of absorption of gentamicin from the peritoneum into the systemic circulation and vice versa. After intraperitoneal instillation of 1 mg/kg in the CAPD fluid during a 6-hr dwell time, the antibiotic appeared in the serum within 15 min in four of five patients. Peak serum concentrations ranged between 1.6 and 7.2 mg/l(mean +/- SD = 3.52 +/- 2.22) in all five patients and the time to reach peak concentration was 3.8 +/- 1.5 hr. Peritoneal gentamicin clearance was 13 ml/min. Percent extraction of gentamicin from the PD fluid within the 6 hr of intraperitoneal exposure ranged from 65% to 100% (mean +/- SD = 86.8 +/- 13.2). The fraction of the intraperitoneal dose absorbed into systemic circulation was found to be 0.84 independently by calculating the ratio of AUCip and AUCiv. When the same dose of gentamicin was injected intravenously (1 mg/kg), no gentamicin could be detected in the peritoneal fluid in three of five patients and only a very small amount of the drug was present for a brief period of time in the remaining two. The kinetic parameters of intravenous gentamicin were: volume of distribution, 0.3 l/kg; elimination rate constant, 0.028 hr(-1), plasma clearance 0.009 l/kg . min(-1), and half-life 27.4 hr. In two patients with acute peritonitis treated with intraperitoneal gentamicin, peak serum concentrations were found to range between 3.5 and 4.5 mg/l. These data suggest that gentamicin is rapidly absorbed from the peritoneal fluid into the blood compartment, but that occurrence of the reverse exchange is negligible. Thus, CAPD would not be expected to alter the elimination characteristics of intravenous gentamicin. Instillation of gentamicin in CAPD fluid may allow rapid absorption to reach therapeutic serum concentrations.

Familial islet cell tumors in Von Hippel-Lindau's disease.

Von Hippel-Lindau's Disease is an hereditary disorder characterized by the development of hemangioblastomas of the cerebellum and retina and a variety of cystic and neoplastic lesions of other organs such as renal cell carcinoma and pheochromocytoma. In a single generation of a family with Von Hippel-Lindau's disease, all four siblings developed lesions classically associated with the complex. Additionally, two of the four developed islet cell tumors of the pancreas, one in one patient and five in the other. While a familial incidence of islet cell tumors is known in multiple endocrine adenomatosis, type I and Zollinger-Ellison syndrome, such a familial occurrence has been heretofore unrecorded in the Von Hippel-Lindau complex.