Haemolytic anaemia and renal failure associated with antibodies to trimethoprim and sulfamethoxazole.

AIM: The aim of this study was to support a clinical diagnosis of drug-induced immune haemolytic anaemia (DIIHA). BACKGROUND: DIIHA is rare and has only been described twice with the antibiotic combination of trimethoprim (TMP) and sulfamethoxazole (SMX). METHODS/MATERIALS: Serologic tests for drug antibodies were performed using methods previously published by our laboratory. RESULTS: A 44-year-old woman experienced body aches, chills, chest pressure, nausea and a rash while receiving TMP-SMX; a week later her haemoglobin was low and she was in renal failure. At the hospital, the direct antiglobulin test (DAT) was positive (C3 only) and the serum reacted with all red blood cells (RBCs) by the gel method only (TMP-SMX is present in the RBC diluent used for the gel method). At the Red Cross immunohaematology laboratory, the patient's serum was reactive in the presence of TMP-SMX (haemolysis and positive antiglobulin test), pure TMP (positive antiglobulin test using anti-IgG only) and pure SMX (haemolysis and positive antiglobulin test using both anti-IgG and anti-C3). The patient was treated with transfusions and haemodialysis and was discharged after a week in stable condition. CONCLUSION: We describe a patient who appeared to have haemolytic anaemia and renal failure associated with antibodies to both TMP and SMX.

Transfusion-related sepsis due to Serratia liquefaciens in the United States.

BACKGROUND: Severe, often fatal, transfusion reactions due to bacterial contamination of blood components continue to occur. Serratia liquefaciens, an unusual human pathogen, is a recently recognized potential cause of transfusion-related sepsis. CASE REPORTS: Five episodes of transfusion-related sepsis and endotoxic shock due to S. liquefaciens were reported to the CDC from July 1992 through January 1999. One episode has been described. The remaining four, all fatal, are described here: three associated with RBC transfusion and one associated with transfusion of platelets. In each instance, the source of contamination could not be found. The implicated units tended to be older (mean RBC age 28 days), and visual discoloration was noted in each RBC unit, although usually in retrospect. CONCLUSION: S. liquefaciens is an increasingly recognized cause of transfusion-related sepsis and is associated with a high mortality rate. S. liquefaciens can contaminate both RBCs and platelets, but the mechanism(s) of contamination remain unknown. Increased attention to pretransfusion visual inspection may avert the transfusion of some S. liquefaciens-contaminated RBC units. However, more sensitive rapid diagnostic tests are needed to further reduce the risk of transfusion-related sepsis and endotoxic shock.

Geomicrobiology of subglacial ice above Lake Vostok, Antarctica.

Data from ice 3590 meters below Vostok Station indicate that the ice was accreted from liquid water associated with Lake Vostok. Microbes were observed at concentrations ranging from 2.8 x 10(3) to 3.6 x 10(4) cells per milliliter; no biological incorporation of selected organic substrates or bicarbonate was detected. Bacterial 16S ribosomal DNA genes revealed low diversity in the gene population. The phylotypes were closely related to extant members of the alpha- and beta-Proteobacteria and the Actinomycetes. Extrapolation of the data from accretion ice to Lake Vostok implies that Lake Vostok may support a microbial population, despite more than 10(6) years of isolation from the atmosphere.

Separation of lipoproteins by capillary isotachophoresis combined with enzymatic derivatization of cholesterol and triglycerides.

Combining specific enzymatic derivatization of cholesterol or triglycerides with capillary isotachophoresis (CITP), human serum lipoproteins are separated into 14 lipoprotein subfractions, monitored and quantitated by direct capillary UV detection. By comparing the separation patterns of human serum with the patterns of lipoprotein particles isolated by sequential ultracentrifugation it became evident that peaks 1-5 represent lipoproteins of the high density lipoprotein (HDL) fraction, peaks 6-8 embody the very low density lipoprotein (VLDL) fraction and chylomicrons, and peaks 7-14 represent the low density lipoprotein (LDL) fraction. Peaks 7 and 8 were found in the VLDL as well as in the LDL fraction. Using triglyceride-specific staining peaks 6-8 occurred prominently; and with cholesterol-specific staining, peaks 1-5 and 7-14 were prominent. The coefficient of variation, for the sum of the peak heights of a pooled serum, was 3.94 for triglyceride-specific staining and 2.32 for cholesterol-specific staining. A linearity range between 0.23 and 2.29 mM/L was found for triglyceride-specific staining and between 0.043 and 4.33 mM/L for cholesterol-specific staining. The practicability of the method was evaluated (i) using blood of humans before and 45 min after an oral fat load. Triglyceride-specific staining revealed a prominent increase in the VLDL fraction and chylomicrones containing peaks 6 and 7, and a minor increase in the HDL fraction containing peaks 3 and 4, and (ii) in patients with manifest hypothyroidism before and after thyroxine therapy. Cholesterol-specific staining demonstrated a massive decrease in the first peak of the HDL fraction and in peaks 9 and 11 of the LDL fraction regarding the hypo versus hyperthyroid state.

Vasopressor hormone response following mesenteric traction during major abdominal surgery.

BACKGROUND: We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI2) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. METHODS: In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGF1 alpha (stabile metabolite of PGI2), TXB2 (stabile metabolite of thromboxane A2) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. RESULTS: Following MT, arterial hypotension occurred along with a substantial PGI2 release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF1 alpha (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P = 0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB2 (164 (87) vs. 58 (1) ng/L, P = 0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P = 0.001), AVP (41 +/- (18) vs. 12 (7) ng/L, P = 0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. CONCLUSION: Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI2 release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A2, presumably contributing to hemodynamic stability within 30 min after MT.

Ibuprofen does not impair renal function in patients undergoing infrarenal aortic surgery with epidural anaesthesia.

OBJECTIVE: To investigate the effect of preoperative ibuprofen administration on renal function during and after infrarenal aortic surgery under thoracolumbar epidural anaesthesia (EPA). DESIGN: A prospective randomised, double-blinded clinical study. SETTING: Operation room and intensive care unit in a university hospital. PATIENTS: Twenty-six consecutive patients scheduled for elective infrarenal aortic surgery. INTERVENTIONS: The patients were prospectively randomised to receive 400 mg ibuprofen intravenously (i.v.) or a placebo aliquot before surgery. MEASUREMENTS AND RESULTS: We assessed renal function by calculating creatinine clearance, and fractional sodium excretion before surgery (baseline), 1 h after cross-clamping (intraoperative), 6 h after cross-clamping (postoperative) and 24 h after cross-clamping (on the 1 st postoperative day). At each point in time, we additionally registered haemodynamics and determined the plasma concentration of 6-keto-PGF1alpha (stable metabolite of prostacyclin, PGI2), bicyclic PGE2 (stable metabolite of PGE1 E2), active renin, aldosterone and vasopressin by radioimmunoassays. Throughout the observation period the renal function parameters mostly remained within the normal range without a significant difference between ibuprofen- and placebo-treated patients (creatinine clearance: baseline 41 +/- 3 vs 38 +/- 6, intraoperative 57 +/- 8 vs 64 +/- 11, postoperative 64 +/- 9 vs 56 +/- 9, first postoperative day 43 +/- 5 vs 47 +/- 6 ml x min x m(-2), means +/- SEM). The plasma levels of 6-keto-PGF1alpha (68 +/- 8 vs 380 +/- 71* ng x l(-1)), bicyclic PGE2 (57 +/- 5 vs 88 +/- 9* ng x l(-1)) and vasopressin (14 +/- 7 vs 45 +/- 10* ng x l(-1), p < 0.0125), however, were significantly higher during the intraoperative period in the placebo-treated patients. CONCLUSION: The inhibition of endogenous prostaglandin release by ibuprofen does not substantially impair renal function during infrarenal aortic surgery under EPA.

The impact of prostanoids on pulmonary gas exchange during abdominal surgery with mesenteric traction.

We investigated the effect of intravenous (iv) ibuprofen on prostanoid release and on pulmonary gas exchange after abdominal mesenteric traction (MT) during either abdominal aortic surgery or pancreas resection. In a prospective, randomized, double-blind study, 400 mg ibuprofen (pancreas n = 13, aorta n = 13) or a placebo (pancreas n = 13, aorta n = 13) was administered iv before skin incision. MT was applied uniformly. The prostanoid plasma concentrations, venous admixture (Q(va)/Q(t)), and PaO2/FIO2 ratio were determined at baseline (before MT) and 5, 15, 45, and 90 min after MT. Patients who underwent aortic surgery were older and exhibited a lower preoperative PaO2 than those who underwent pancreas resection. Placebo-treated patients revealed a 30-fold peak increase in 6-keto-prostaglandin F1alpha (stable metabolite of prostacyclin) levels after intentional MT during aortic as well as pancreatic operations. This response was accompanied by an increase in Q(va)/Q(t) (ibuprofen: pancreas 7% +/- 1%, aorta 14% +/- 2%; placebo: pancreas 16% +/- 3%, aorta 26% +/- 3%/15 min after MT [mean +/- SEM, P < 0.05, placebo vs ibuprofen]), which resulted in decreased PaO2/ FIO2 ratio only in the aortic surgery patients (ibuprofen: 310 +/- 19; placebo: 237 +/- 24 15 min after MT, [mean +/- SEM, P < 0.05]). The authors conclude that ibuprofen-pretreated patients demonstrated almost constant prostanoid levels without changes in pulmonary gas exchange after MT.

Impact of light regimes on productivity patterns of benthic microbial mats in an antarctic lake: a modeling study.

Filamentous cyanobacteria often dominate benthic microbial communities of antarctic lakes and usually exhibit saturation of photosynthesis at light intensities approximately 100 microEinst m-2 s-1. Incident light regimes are controlled by ice and snow accumulations overlaying water columns during much of the year. Thus, light availability to microbial mats is often below saturation intensity and is strongly influenced by modest changes in climatic factors. A model of net primary production for benthic mat communities of the subantarctic Sombre Lake, Signy Island, was developed (1) to evaluate depth-specific productivities of mat communities, (2) to test the relative importances of model parameters to mat production, and (3) to explore the potential impacts of climate change on mat production as manifested through changes in light regime. Simulated rates of net primary production corresponded to observations on a daily basis (approximately 1-4 micrograms C fixed mg-1 ash-free DW of mat d-1) but were an order of magnitude lower than estimates of net annual production based on field measurements (< or = 3 vs. 11-45 g C m-2 yr-1, respectively). Close examination suggested that the simulated values were more plausible. A detailed sensitivity analysis of model behavior revealed that variations in the time of ice and snow melt in spring accounted for 40-60% of the total variation in model behavior, emphasizing the importance of climatic factors to net primary production of mat communities and the sensitivity of mat production to climate change.

Perioperative endotoxemia and bacterial translocation during major abdominal surgery: evidence for the protective effect of endogenous prostacyclin?

OBJECTIVE: To investigate the potential role of endogenous prostacyclin (PGI2) released after mesenteric traction during major abdominal surgery on perioperative endotoxemia and bacterial translocation. DESIGN: Prospective, randomized, double-blind clinical study. SETTING: Operating room and surgical intensive care unit in a university hospital. PATIENTS: Fifty consecutive patients scheduled for major abdominal surgery (pancreas resection, abdominal aortic surgery). INTERVENTIONS: Fifteen minutes before skin incision, either 400 mg of ibuprofen or a placebo equivalent were administered intravenously. Immediately after peritoneal incision, eventration and action of the small bowel was intentionally performed in a uniform fashion. MEASUREMENTS AND MAIN RESULTS: Baseline values were obtained before induction of anesthesia. Additional measurements, along with assessments of hemodynamics and gas exchange, were performed before incision of the peritoneum and at 5, 30, and 45 mins and 3, 6, and 24 hrs after mesenteric traction. Arterial plasma concentrations of 6-keto-prostaglandin F1 alpha and thromboxane B2 (stable metabolites of PGI2 and thromboxane A2) were determined by radioimmunoassay. Endotoxin was measured by limulus amebocyte lysate test. Mesenteric lymph nodes were sampled in 31 patients (ibuprofen n = 14, placebo n = 17) and sent for culture under sterile conditions. Transient hypotension and a marked increase of plasma 6-keto-prostaglandin F1 alpha concentrations occurred up to 6 hrs after mesenteric traction in untreated patients with median peak concentrations (2243 vs. 72 ng/L [p < .0001, placebo vs. ibuprofen], observed 5 mins after mesenteric traction). Endotoxemia occurred in both study groups. However, after mesenteric traction, plasma endotoxin concentrations were significantly higher in the ibuprofen group. Median peak concentrations (0.12 vs. 0.27 EU/mL [p < .001, placebo vs. ibuprofen]) were observed 3 hrs after mesenteric traction. Gram-negative bacteria in mesenteric lymph nodes were detected exclusively in the ibuprofen group (n = 5, p < .01). CONCLUSIONS: In ibuprofen-pretreated patients, significantly higher endotoxin concentrations as well as bacterial translocation to mesenteric lymph nodes occurred, despite the absence of a transient decrease in mean arterial pressure that had been associated with PGI2 release. Therefore, we hypothesized that during major abdominal surgery, endogenous PGI2 released in response to mesenteric traction may play a crucial role in maintaining splanchnic microcirculation and thus preserving gut mucosal barrier function.

Fetal transfusion therapy.

Rapid advances are occurring in the diagnosis and treatment of the fetus with a red blood cell or platelet cytopenia. Noninvasive methods of monitoring the alloimmunized pregnancy, invasive methods such as amniocentesis and cordocentesis, and intrauterine transfusion therapy of both red cells and platelets, are being further refined to allow the prompt recognition and treatment of fetal cytopenias. Specialized centers have now accrued a large experience in the management of the fetus severely affected by alloimmunization. Advances in ultrasound, blood banking techniques, and genetic engineering technology have spurred the most recent advances. The indications for diagnosis, timing and frequency of invasive procedures for treatment, and technical considerations regarding preparation of blood products and volume of transfusion, are outlined in this review. Polymerase chain reaction (PCR) determination of fetal Rh(D) genotype by chorionic villus sampling or amniocentesis in the first or second trimesters is a recent clinically useful advance. The advent of hematopoietic stem cell transplantation and the potential for gene therapy are exciting advances in the treatment and prevention of hematopoietic diseases, including, but not limited, to the fetal cytopenias.

Unchanged 5'-deiodinating activity during the induction of a nonthyroidal illness.

We investigated the formation of a "nonthyroidal illness" (NTI) in pigs undergoing ventricular fibrillation (VF) and resuscitation. Seven minutes after VF twenty-one pigs received either Epinephrine (E: 45 micrograms/kg B.W.; n = 7), Norepinephrine (NE: 45 micrograms/kg B.W.; n = 7), or Vasopressin (VP: 0.8 U/kg B.W.; n = 7). We determined the serum concentrations (sc) of total T4 (TT4), FT4, total T3 (TT3) and rT3 120 min before, during (t0), and 5, 15, 60 and 120 min after VF. At the end of the observation period we figured out the in-vitro T3-generation (kM, Vmax), the in-vitro rT3-generation, the in-vitro rT3-decomposition (kM, Vmax) and the content of cytosolic sulfhydryls (total sulfhydryls, non-protein bound sulfhydryls) in liver and kidney specimen. Animals not undergoing VF served as controls (C) for parameters measured in the intracellular compartment. TT4- and TT3-sc decreased to 3.3 +/- 0.6 micrograms/dl (p < 0.05, vs. t0) and 15.2 +/- 4.1 ng/dl (p < 0.05, vs t0), resp. FT4-sc remained stable for five minutes (2.63 +/- 0.41 ng/dl) before declining to 1.8 +/- 0.39 ng/dl (p < 0.05, vs. t0). The rT3-sc raised finally to 46.9 +/- 7.3 ng/dl (p < 0.05, vs t0). Iodothyronine sc did not exhibit differences between E-, NE- and VP-treatment. Neither in-vitro T3-generation, nor in-vitro rT3-generation, nor in-vitro rT3-decomposition nor intracellular sulfhydryl content were affected by the events of VF and resuscitation as compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of thoracic epidural anesthesia on the pathophysiology of the eventration syndrome]. / Einfluss der thorakalen Epiduralanästhesie auf die Pathophysiologie des Eventrationssyndroms.

Abdominal mesenteric traction (MT) results in decreased mean arterial pressure (MAP), systemic vascular resistance (SVR) and increased cardiac output (CO). This response is induced by a considerable release of prostacyclin (PGI2). Precipitous falls in systemic arterial pressure related to central and/or autonomic nervous reflex arcs also have been described during operations on the upper abdominal viscera. Those hypotensive responses to visceral traction appear to be transmitted along afferent fibres contained within the splanchnic nerves. We investigated the influence of supplementary thoracic epidural anaesthesia on mesenteric traction response during major abdominal surgery. METHODS. With the approval of the Human Investigation Review Board we studied 40 patients scheduled for major abdominal surgery (infrarenal aortic, gastrointestinal and pancreatic surgery) according to a prospective, randomized double-blinded protocol. Patients were randomized to two different anaesthetic regimens. Patients in group 1 received general anaesthesia (GA n = 20) with 0.1-0.15 mg/kg midazolam and 10 micrograms/kg fentanyl prior to skin incision. Maintenance included 65% nitric oxide in oxygen and 0.1 mg increments of fentanyl as required. Group 2 patients (EA n = 20) underwent a combined technique of dose-reduced general anaesthesia and supplementary continuous, thoracic epidural anaesthesia (bupivacaine 0.25%, sensory blockade T4 to L1-3). In both anaesthesia groups ibuprofen (400 mg i.v.) or a placebo equivalent was administered 15 min before the induction of anaesthesia. MT was applied in a uniform fashion. Baseline values preceded the incision of the peritoneum. Further assessments followed 5, 15 and 30 min after MT. The plasma concentrations of 6-keto-PGF1 alpha (stable metabolite of PGI2), TXB2 (stable metabolite of thromboxane), PGF2 alpha, KH2-PGF2 alpha (stable metabolite of PGF2 alpha) were determined by radioimmunoassay. At all assessments we recorded systolic and diastolic blood pressure, heart rate and measured arterial blood gases. Statistical analyses were performed using three-factor ANOVA for repeated measurements after log(x) transformation. A P-value of less than 0.05 was considered significant when the Bonferroni-Holm adjustment was applied. RESULTS. Patients with supplementary epidural anaesthesia demonstrated lower systolic (P = 0.0001) and diastolic (P = 0.006) blood pressure than those in the GA group. Nevertheless, in untreated patients in the EA and GA group there was a significant decrease of about 20-30% in systolic and diastolic blood pressure (P = 0.0001) after mesenteric traction. Irrespective of the anaesthetic procedure, paO2 (P = 0.0001) decreased after mesenteric traction in the placebo group. The control patients in the GA group exhibited a more pronounced increase in heart rate after MT. After traction on the mesentery a significant 20- to 30-fold increase in 6-keto-PGF1 alpha plasma concentrations occurred in the placebo group: GA group 1950/58 (5 min), 1574/59 (15 min) 858/66 (30 min) ng/l, P < 0.0001; EA group: 2002/106 (5 min), 2955/107 (15 min) 1807/70 (30 min) ng/l, P < 0.0001, for placebo vs ibuprofen. There was no statistically significant difference between the two anaesthetic procedures used. In ibuprofen-pretreated patients haemodynamics and paO2 values were stable, while 6-keto-PGF1 alpha plasma concentrations remained within the normal range. CONCLUSION. Our data clearly indicate that the mesenteric traction response consists in relevant haemodynamic alterations and a significant decrease of paO2. Stable haemodynamics and paO2 following cyclooxygenase inhibition signify an action mediated by prostacyclin. Deafferentation of the splanchnic nerves by supplementary thoracic epidural anaesthesia did not influence either prostacyclin release or the decrease in blood pressure and paO2 after traction on the mesentery root...

The first reported case of anti-Dob causing an acute hemolytic transfusion reaction.

The antibodies of the Dombrock blood group system have only rarely been encountered in transfusion practice, and anti-Dob has not previously been implicated in an acute hemolytic transfusion reaction. We have encountered the first such case involving a chronically transfused black female with hemoglobin SS disease and multiple antibodies in her serum. During a previous admission for sickle cell crisis, the patient received 3 units of compatible blood with no untoward effects. Serum obtained 21 days later contained, in addition to the known antibodies, anti-S plus an unidentified antibody showing characteristics of HTLA. Blood lacking the E, K1, Fy(a), Jk(b) and S antigens was obtained, and 2 least incompatible units were transfused. While administering the second unit, the patient complained of fever and low back pain, and hemoglobinemia was detected. Anti-Dob was identified in the post-reaction samples by absorption-elution tests, and the patient was confirmed to be Do(a+b-). The first unit transfused during this hemolytic episode tested Do (b+). This case, and a similar case involving anti-Doa reported in 1986, strengthens the belief that Dombrock antibodies are clinically significant and illustrates the need for their differentiation, prior to transfusion from less clinically significant HTLA antibodies.

Thyrotropin-releasing hormone: pharmacokinetic and pharmacodynamic properties in chronic renal failure.

The pharmacokinetics of thyrotropin-releasing hormone (TRH) were determined following a single i.v. administration in ten patients with chronic renal failure (CRF) maintained on chronic hemodialysis and in six normal subjects. A TRH-test (200 micrograms) was performed in all subjects on nondialysis days and was followed by sequential venous blood sampling at 0, 2, 5, 10, 20, 30 and 60 min. Plasma TRH and serum concentrations of TSH, T4, FT4 and T3 were measured by specific and sensitive RIA's. Serum thyroid hormone concentrations were lower in the hemodialysis patients than in the normals (p < 0.001). Basal TRH and TSH levels were similar in patients and in controls, however, a blunted response of TSH to TRH in CRF (3.8 +/- 2.4 vs. 11.2 +/- 2.6 mU/l, p < 0.001) was observed. Mean peak TRH concentrations (Cmax) were 34.445 (11.085, SD) fmoles/ml in CRF and only (13,400 (1.020) in the normals 2 min after TRH administration (tmax). The mean elimination half-life (t1/2) of TRH was 16 min in CRF and 6.5 min in normals (p < 0.001). The metabolic clearance rate (MCR) was markedly lowered in CRF, 58.3 (19.1) compared to normals (82.2 [15.3] l/m2/day, p < 0.001). The area under the plasma concentration-time curve (AUC) was 57.529 (28.562) fmoles.ml-1.min in CRF and 37.339 (5.026) (p < 0.005) in normals. These findings indicate that the pharmacokinetic properties of TRH are impaired in CRF. The kidney might be an important catabolic organ for exogenous TRH. Dosing schedules of TRH require possible adaptation to renal function.

Serum angiotensin-converting enzyme activity and active renin plasma concentrations in insulin-dependent diabetes mellitus.

We report here the alterations of serum angiotensin-converting enzyme activity (S-ACE) and of active renin plasma concentrations (ARPC) in 41 insulin-dependent diabetes mellitus (IDDM) patients compared with those of 26 control subjects. The IDDM patients had S-ACE activity (54 +/- 16 I.E.) in the upper normal range (controls, 39 +/- 7). When the patients were subclassified according to their diabetic complications, a significant increase of S-ACE within the IDDM group compared to the controls was observed in patients with nephropathy (68 +/- 13, P less than 0.001) with persistent proteinuria and with retinopathy (63 +/- 14, P less than 0.001). A significant correlation was found between proteinuria and S-ACE (r = 0.98, P less than 0.001) and between retinopathy and S-ACE levels (r = 64, P less than 0.001). No correlation between blood pressure and S-ACE or between blood glucose and S-ACE was observed. The ARPC were within the normal range in the IDDM (21 +/- 9 ng/l) and in control (19 +/- 3) groups. No correlations between ARPC and blood pressure or blood glucose or the degree of diabetic complications were registered. These data show that S-ACE activity is elevated in IDDM patients with nephropathy-proteinuria and/or with retinopathy and the circulating renin may not represent the renal renin-angiotensin vascular system.

Thyroid status and hepatic thyroxine deiodinating activity under high-dose long-term nitrendipine.

The influence of high doses of oral nitrendipine on the hypophyseal-thyroid axis and on peripheral thyroxine metabolism was studied in baboons. Administration of 320 mg oral nitrendipine per kg body weight (b.wt.) for three months caused a hypothyroid state with decreased values for thyroxine and reverse triiodothyronine, elevated TSH, but unchanged triiodothyronine; the lower doses investigated (24 and 48 mg/kg b.wt.) were without any effect. High doses of nitrendipine concomitantly increased hepatic 5'-deiodinating activity by a rise in Vmax, which could be attributed to an increase in the deiodinating enzyme content. Normal T3 serum levels in the presence of low T4 serum concentrations under high dose nitrendipine can be ascribed, at least in part, to the enhanced peripheral 5'-deiodination.

Comparative effects of dopamine and dobutamine on glucoregulation in a rat model.

The influence of dopamine as compared with dobutamine on glucose homeostasis has been assessed in thyroidectomized euthyroid rats. Both sympathomimetic agents were given intravenously over 6 h at four dosages, varying from 2 to 30 micrograms.kg-1.min-1. Immediately before the end of the infusion period, serum concentrations of glucose and insulin as well as plasma glucagon concentrations were measured. Dobutamine infusions did not exert any influence on these parameters. At a dose of 7.5 micrograms.kg-1.min-1, dopamine infusion caused a decrease in glucose concentrations, accompanied by a rise of glucagon and insulin levels. Glucose levels were significantly increased in the presence of unaltered insulin and decreasing glucagon levels at higher dopamine doses. The rise in glucose levels was reversed by 8 micrograms.kg-1.min-1 and inverted to a decrease by 12 micrograms.kg-1.min-1 of the alpha-adrenergic blocking agent phentolamine, simultaneously infused with 15 micrograms.kg-1.min-1 dopamine, while the insulin levels were increased and glucagon levels remained elevated. These findings demonstrate that dopamine acts on glucoregulation divergently, according to the dosage applied. The data suggest that dopamine rather than dobutamine treatment may disturb glucose homeostasis.

Thyroxine and reverse T3 5'deiodination in the cells of human adipose tissue.

The intracellular 5'deiodination (5'D) of T4 and rT3 has been investigated in human adipose tissue. We studied 5'D in intact adipose tissue, its morphological components and in 3T3-L1-cells. 5'D as assessed by T3-production out of T4 and by rT3-decomposition was not inhibited by propylthiouracil (PTU), but by iopodate (IOP). The apparent Michaelis constants were kM = 3 nM for rT3 and kM = 1 microM for T4. The rT3-degradation was linear over 25 h (115 pg/h.mg (prot.)) both at 37 degrees C and at 4 degrees C. The same type of 5'D was observed in adipocytes, stromal-vascular cells and in 3T3-L1-cells regarding T4 to T3 degradation (244 +/- 30, 181 +/- 27, 227 +/- 37 pg T3/mg.min), resp.; PTU did not exert any influence upon 5'D in the cells investigated. We conclude, that i. the intracellular generation of T3 in adipose tissue does not derive from type I deiodination; ii. 5'D in adipocyte precursors and differentiated adipocytes is identical and iii. there is no difference between human cells and 3T3-L1-cells regarding 5'D.

Hepatic sulfhydryl content under adrenergic stimulation in male rats.

The influence of a series of sympathomimetic agents on the liver content of non protein bound thiol groups (NP-SH), mainly representing glutathione, has been assessed in the male rat. The rats were intravenously and/or subcutaneously infused over 6 h at different dosages either with dopamine, dobutamine, epinephrine, terbutaline, or phentolamine, or simultaneously with dopamine and phentolamine, or with epinephrine and phentolamine. Besides NP-SH, total sulfhydryl group content was measured in liver cytosol, while glucose and insulin concentrations were determined in the serum. Liver NP-SH content was significantly decreased by epinephrine. This decrease was abolished and even inverted to an increase, when appropriate doses of phentolamine were infused simultaneously. Dopamine caused a rise in NP-SH content at a dose rate of 7.5 micrograms/kg.min, while lower and higher dose rates of dopamine exerted not any influence on liver NP-SH. When phentolamine was concomitantly infused with 15 micrograms/kg.min of dopamine, NP-SH was significantly elevated. Phentolamine, when infused exclusively, increased NP-SH as well, while it was not influenced, however, by terbutaline or dobutamine at any dosage. Cytosolic total sulfhydryls were found to be unaltered across all experimental groups. When the NP-SH values are related to the corresponding serum insulin levels, a close and linear relationship becomes evident. The study demonstrates, that some sympathomimetic agents can exert a considerable influence on hepatic non protein bound thiol content. The data suggest, that the varying liver NP-SH content under adrenergic drugs is primarily related to changes in serum insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)