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Biomedical subjects

L Kuhnert

Publications and source records attributed to L Kuhnert.

7 recordsLinked to original sources
PubMed1996

(Carboxyalkyl)benzyl propargyl ethers as selective inhibitors of leukocyte-type 12-lipoxygenases.

A series of (carboxyalkyl)benzyl propargyl ethers was synthesized and tested as inhibitors of 12-lipoxygenase (12-LO) from porcine leukocyte cytosol. Optimum activity was displayed by 3-[4-[(2-tridecynyloxy)methyl]phenyl]propanoic acid. Altering the length of the alkyl side chain attached to the acetylenic group reduced activity. Changing the substitution pattern in the (carboxyalkyl)benzyl group from para to meta or ortho also reduced activity. Analogs in which the triple bond was replaced by a double bond or an allene displayed reduced activity, whereas fully saturated analogs were inactive. High concentrations (10 microM) of the most potent acetylenic (carboxylalkyl)benzyl ethers did not inhibit human platelet 12-LO, human neutrophil 5-LO, rabbit reticulocyte 15-LO, or soybean 15-LO. Thus, this class of compounds represents the first example of isoform specific LO inhibitors.

Animals↗
PubMed1988

Ventricular ectopic activity with diuretic therapy.

The arrhythmogenic potential of diuretic-induced hypokalemia in patients with uncomplicated hypertension has been controversial. Thirty-two hypertensive patients with previous diuretic-induced hypokalemia, normal 24-hour ambulatory ECG monitoring, and normal exercise testing were treated with 100 mg hydrochlorothiazide (HCTZ) daily (Group 1) to induce hypokalemia or with a combination of HCTZ with amiloride (Group 2) to attempt to maintain plasma potassium levels in the normal range during diuretic therapy. Those Group 1 patients (Group 1A) with increased ventricular ectopic activity (VEA) during HCTZ therapy were subsequently potassium-repleted with amiloride and with supplemental potassium chloride to evaluate the effect of these treatments on VEA. One Group 1 patient died suddenly after 12 days of HCTZ therapy. Autopsy findings suggested an arrhythmic death. Six Group 1 patients who had increased VEA with HCTZ treatment had reductions in VEA with amiloride or supplemental potassium chloride. Group 2 patients did not have a significant increase in VEA. Thus, diuretic therapy appears to cause VEA primarily by electrolyte changes that are induced.

Adult↗
PubMed1983

Isoflurane and enflurane-induced hepatic necrosis in triiodothyronine-pretreated rats.

Exposure of triiodothyronine (T3)-pretreated rats to 1.3% isoflurane, 1.8% enflurane, or 1% halothane in 21% oxygen (air) for two hours resulted in hepatic centrilobular necrosis. The incidence of the liver lesion was 28, 24, and 92% after exposure to isoflurane, enflurane, and halothane, respectively. Histopathologic grading indicated that the necrosis was more severe after halothane than after isoflurane or enflurane anesthesia. No lesion was observed in livers prepared from non-anesthetized T3-pretreated rats or in livers prepared from rats which were pretreated with the vehicle for T3 and then anesthetized with either isoflurane, enflurane, or halothane. Hepatic necrosis was not observed in vehicle-treated rats exposed to isoflurane in 12% oxygen or in vehicle-treated rats that were deprived of food for 12 hours prior to exposure to isoflurane under hypoxic conditions. Food restriction to maintain the body weight gain of vehicle-treated rats similar to that of T3-treated rats did not result in hepatotoxicity after exposure to halothane in 21% oxygen. Liver necrosis did not occur in pentobarbital anesthetized (40 mg/kg, intraperitoneally) T3-pretreated rats. These results indicate that isoflurane and enflurane, like halothane, can induce hepatic centrilobular necrosis in T3-pretreated rats. The mechanism for liver toxicity of these volatile anesthetic agents in this model remains to be determined.

Animals↗
PubMed1983

Further studies on the hypernoradrenergic state of treated hypertensives: effect of captopril.

We investigated the effect of captopril on plasma norepinephrine concentration and blood pressure in two groups of hypertensive patients. One group consisted of five severely hypertensive patients rendered hypernoradrenergic by administration of a minoxidil-propranolol-diuretic regimen. The other group was ten untreated mildly hypertensive patients. Two hours after 12.5mg of captopril, blood pressure was lowered (p less than .05) in four of the five hypernoradrenergic patients from 180 +/- 8/102 +/- 8 to 132 +/- 7/77 +/- 8 mmHg. Chronic administration of 100-150mg of captopril tid caused no further blood pressure reduction. Precaptopril plasma norepinephrine concentration was 925 +/- 206 and two hours after the 12.5mg dose was 807 +/- 80 pg/ml. Three months later having advanced the dose to 300-450 mg/day it was lower (p less than .05) at 752 pg/ml. The acute blood pressure response correlated (r = -0.72, p less than .001) with the precaptopril plasma norepinephrine. Precaptopril blood pressure in the mild hypertensive patients was 146 +/- 4/98 +/- 1, after a 25-100mg dose it was 137 +/- 6/91 +/- 2 (diastolic p less than .05) and at two months with the same captopril dose bid it was 141 +/- 8/88 +/- 4 mmHg (diastolic p less than .01). Corresponding initial PNE was 425 +/- 72, two hours after captopril 405 +/- 47 and 310 +/- 63 pg/ml (p less than .05) with chronic administration. Thus, captopril lowers blood pressure in both hypernoradrenergic and eunoradrenergic hypertensive patients without increasing plasma norepinephrine suggesting some unique dampening effect of this drug on the sympathetic nervous system. Also, addition of captopril to triple therapy lowered blood pressure in proportion to plasma norepinephrine levels suggesting importance to its action on this sympathetic nervous system effector.

Blood Pressure↗
PubMed1981

Diuretic-induced ventricular ectopic activity.

The need to avoid hypokalemia during diuretic therapy in nondigitalized patients has been questioned. Twenty-one patients with (1) mild essential hypertension, (2) plasma potassium of less than 3.5 meq/liter during previous diuretic treatment, and (3) normal findings [less than 6 unifocal ventricular premature beats/hour] on 24-hour ambulatory electrocardiographic monitoring and exercise testing were treated with hydrochlorothiazide (50 mg twice a day) for four weeks and then ambulatory electrocardiographic monitoring and exercise testing were repeated. Ambulatory electrocardiographic monitoring revealed that ventricular ectopic activity developed in seven patients and complex ventricular ectopic activity (multifocal ventricular premature beats, ventricular couplets and/or ventricular tachycardia) in four. Only two of these seven had ventricular ectopic activity during exercise testing while they were hypokalemic. Potassium repletion in these seven patients with spironolactone abolished complex ventricular ectopic activity and reduced unifocal ventricular premature beats significantly (p less than 0.01) from an average of 71.2 ventricular premature beats/hour/patient during hydrochlorothiazide treatment to 5.4 ventricular premature beats/hour/patient after potassium repletion. Although complex ventricular ectopic activity was more likely to occur with plasma potassium less than 3.0 meq/liter, restoration of normokalemia was required in several patients to abolish residual ventricular ectopic activity. Persistent ventricular ectopic activity in one patient suggested that myocardial injury sustained during hypokalemia may initiate chronic ventricular ectopic activity. Even in nondigitalized patients, the hazard of diuretic-induced ventricular ectopic activity warrants correction of hypokalemia.

Adult↗
PubMedDate not supplied

Further evaluation of saline infusion for the diagnosis of primary aldosteronism.

Normal subjects, normal-renin hypertensive patients, and low-renin hypertensive patients were evaluated by intravenous saline infusion and with a fludrocortisone acetate (Florinef) protocol to clarify diagnostic criteria for primary aldosteronism that are recommended for the saline infusion protocol. The patients consumed a 200 mEq sodium, 70 mEq potassium diet for 6 days, and on the last 3 days received Florinef 0.5 mg orally twice daily. On Days 3 and 6, urinary aldosterone and tetrahydroaldosterone excretions were determined, and on Days 4 and 7 plasma aldosterone (PA) was determined at 0600 after overnight recumbency and at 0800 after 2 hours of walking. Although the level of normal PA suppression by saline infusion has been commonly defined as 10 ng/dl, a value of 5 ng/dl was originally recommended. In 20 normal subjects and 45 normal-renin hypertensive patients, we found that the PA was almost always suppressed below 5 ng/dl. In 18 of 75 low-renin patients including five with aldosterone-producing adenoma (APA), the PA was never suppressed below 10 ng/dl; thus, these 18 patients had classical primary aldosteronism by generally accepted criteria. The Florinef protocol was performed in eight of these 18 patients and was abnormal in all. An abnormal Florinef protocol was also found in seven of 15 patients studied with PA suppression after saline infusion to between 5 and 10 ng/dl, but in only one of 24 patients studied with PA suppression below 5 ng/dl. Additional studies in the subgroup with abnormal results from the Florinef protocol indicated that none of these patients had evidence of APA, so they had nontumorous primary aldosteronism (NTPA).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗