Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: REGULATION OF RENAL TUBULAR SODIUM TRANSPORT BY ANGIOTENSIN II AND ATRIAL NATRIURETIC FACTOR

• 1 The effects of angiotensin II (AngII) on water and electrolyte transport are biphasic and dose-dependent, such that low concentrations (10^?12 to 10^?9 mol/L) stimulate reabsorption and high concentrations (10^?7 to 10^?6 mol/L) inhibit reabsorption. Similar dose-response relationships have been obtained for luminal and peritubular addition of AngII.
• 2 The cellular responses to AngII are mediated via AT₁ receptors coupled via G-regulatory proteins to several possible signal transduction pathways. These include the inhibition of adenylyl cyclase, activation of phospholipases A₂, C or D and Ca²⁺ release in response to inositol-1,4,5,-triphosphate or following Ca²⁺ channel opening induced by the arachidonic acid metabolite 5,6,-epoxy-eicosatrienoic acid. In the brush border membrane, transduction of the AngII signal involves phospholipase A₂, but does not require second messengers.
• 3 Angiotensin II affects transepithelial sodium transport by modulation of Na⁺/H⁺ exchange at the luminal membrane and Na⁺/HCO₃ cotransport, Na⁺/K⁺-ATPase activity and K⁺ conductance at the basolateral membrane.
• 4 Atrial natriuretic factor (ANF) does not appear to affect proximal tubular sodium transport directly, but acts via specific receptors on the basolateral and brush border membranes to raise intracellular cGMP levels and inhibit AngII-stimulated transport.
• 5 It is concluded that there is a receptor-mediated action of ANF on proximal tubule reabsorption acting via elevation of cGMP to inhibit AngII-stimulated sodium transport. This effect is exerted by peptides delivered at both luminal and peritubular sides of the epithelium and provides a basis for the modulation by ANF of proximal glomerulotubular balance. The evidence reviewed supports the concept that in the proximal tubule, AngII and ANF act antagonistically in their roles as regulators of extracellular fluid volume.

     

Liposomes and Nanoparticles in the Treatment of Intracellular Bacterial Infections

The treatment of infections caused by obligate or facultative intracellular microorganisms is difficult because most of the available antibiotics have either poor intracellular diffusion and retention or reduced activity at the acidic pH of the lysosomes. The need for antibiotics with greater intracellular efficacy led to the development of endocytosable drug carriers, such as liposomes and nanoparticles, which mimic the entry path of the bacteria by penetrating the cells into phagosomes or lysosomes. This Review assesses the potential of liposomes and nanoparticles in the targeted antibiotic therapy of intracellular bacterial infections and diseases and the pharmaceutical advantages and limitations of these submicron delivery systems.     

Succinylcholine does not worsen bupivacaine-induced cardiotoxicity in pentobarbital-anaesthetized dogs

The intravascular injection of a large dose of bupivacaine induces electrophysiological cardiac impairment, mainly by slowing ventricular conduction velocity, and haemodynamic depression, by a decrease in myocardial contractility. When cardiotoxicity occurs, succinylcholine rapidly stops convulsions. However, the possible interactions between bupivacaine and succinylcholine on cardiac electrophysiology and haemodynamic status have never been investigated. Thus, we used an experimental electrophysiological model involving closed-chest dogs. Three groups (n = 6) of pentobarbital-anaesthetized dogs were given 0.2 mg.kg-1 atropine iv. Dogs in Group 1 were given saline. The others received 4 mg.kg-1 bupivacaine iv over ten seconds. Dogs in Group 2 were then given saline and those in Group 3 were then given 2 mg.kg-1 succinylcholine iv from one to two minutes after the administration of bupivacaine. The following electrophysiological variables were measured: heart rate represented by RR interval (RR), PR, atria-His (AH), and His-ventricle (HV) intervals, QRS duration, and QT interval corrected for heart rate (QTc). The following haemodynamic variables were measured: mean aortic pressure (MAoP), the peak of the first derivative of left ventricular pressure (LV dP/dt max), and LV end diastolic pressure (LVEDP). Comparison between Groups 1 and 2 showed that bupivacaine induced more than 100% HV interval lengthening and QRS widening (P less than 0.01), prolonged QTc interval by more than 25% (P less than 0.01), and decreased LV dP/dt max by more than 50% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Eight month follow-up of delinquent adolescents: predictors of short-term outcome

Clinicians working with young delinquents are concerned with finding methods to predict recidivism in these subjects. It has not been investigated yet to what extent psychiatric assessment can be of any help in this field. In this study, we investigated whether psychiatric assessment can help to predict recidivism in already delinquent adolescents. By means of semi-structured psychiatric assessment (Child Assessment Schedule), developmental interview of the parents and self-report instruments, we assessed the psychiatric status of 72 delinquent adolescents, adjudicated before the Juvenile Court of Antwerp (Belgium). A follow-up of criminal status after eight months was conducted. Self-report questionnaires by the subjects did not differentiate recidivists from non-recidivists, while parent questionnaires did. Through a semi-structured interview, we found that a diagnosis of conduct disorder significantly predicts recidivism, while subjects with ADHD and substance abuse show a tendency towards more recidivism. We were unable, however, due to the small number of subjects showing a psychiatric disorder (e. g. ADHA and PTSD) unrelated to conduct disorder, to assess the relative contribution of these disorders to the recidivism rate. This study found that psychiatric assessment of delinquent adolescents could be of help in predicting recidivism. The necessity of gathering information from parents and teachers is demonstrated. Future research should include a more extensive group of a delinquent adolescent and should focus on the effect of therapeutic interventions. Received: 29 June 1999 / Accepted: 1 February 2000     

Role of hysteroscopy in the diagnosis and treatment of infertility

UTERINE DISORDERS: Because they can prevent implantation, anomalies within the uterine cavity play an important role in fertility. The uterine disorders most often observed during hysteroscopy and implicated in infertility are adhesions, septa, polyps, submucous myomas, adenomyosis, endometritis, anomalies of the cervical canal, and lesions of the uterotubal junction. EXPLORATIONS: Hysterosalpingography can be used to evaluate tubal permeability but provides inadequate information about the uterine cavity (numerous false-positives and false-negatives). Pelvic ultrasound is especially helpful for diagnosing interstitial anomalies in the uterus. HYSTEROSCOPY: Diagnostic hysteroscopy also has a place in infertility investigations, for it allows direct visualization of the uterine cavity, the endometrial mucus (endometritis, adenomyosis), and the cervical canal. The examination is practiced on a out-patient basis, without anesthesia, using appropriate small-caliber instruments and irrigation with physiological saline. Surgical hysteroscopy is used to treat these anomalies. Patients receive general anesthesia. A high-frequency, low-voltage electric current is used, and glycine for irrigation. This procedure allows resection of submucous myomas and polyps and of septa and adhesions. Some groups use laser beams and irrigation by physiological saline for these treatments. Coagulation of a superficial focal spot of adenomyosis is not useful in infertility therapy. RESULTS: As assessed by the percentage of patients with each indication who subsequently became pregnant, the results of surgical hysteroscopy have been satisfactory: 62 per cent (%) of cases after myomectomy, 66% after section of uterine septa, and 61% after treatment of complicated adhesions. A new exploration of the uterine cavity will be necessary sometime after the surgery to verify the absence of any iatrogenic disorders (adhesions, myomatous fragments).     

Protein feeding pattern does not affect protein retention in young women

This study was undertaken to determine whether a pulse protein feeding pattern was more efficient than a spread pattern to improve protein anabolism in young women as was already shown in elderly women. After a 15-d adaptive period [1.2 g protein/(kg fat-free mass. d)], 16 young women (age 26 +/- 1 y) were given a 14-d diet providing 1.7 g protein/(kg fat-free mass. d), using either a pulse pattern (protein consumed mainly in one meal, n = 8), or a spread pattern (spreading daily protein intake over four meals, n = 8). Nitrogen balance was determined at the end of both the 15-d adaptive and the 14-d experimental periods. Whole-body protein turnover was determined at the end of the 14-d experimental period using [(15)N]glycine as an oral tracer. Nitrogen balance was 17 +/- 5 mg N/(kg fat-free mass. d) during the adaptive period. It was higher during the experimental period, but not significantly different in the women fed the spread or the pulse patterns [59 +/- 12 and 36 +/- 8 mg N/(kg fat-free mass. d) respectively]. No significant effects of the protein feeding pattern were detected on either whole-body protein turnover [5.5 +/- 0.2 vs. 6.1 +/- 0.3 g protein/(kg fat-free mass. d) for spread and pulse pattern, respectively] or whole-body protein synthesis and protein breakdown. Thus, in young women, these protein feeding patterns did not have significantly different effects on protein retention.     

Preventive and curative effect of melatonin on mammary carcinogenesis induced by dimethylbenz[a]anthracene in the female Sprague-Dawley rat

Introduction  

It has been well documented that the pineal hormone, melatonin, which plays a major role in the control of reproduction in mammals, also plays a role in the incidence and growth of breast and mammary cancer. The curative effect of melatonin on the growth of dimethylbenz [a]anthracene-induced (DMBA-induced) mammary adenocarcinoma (ADK) has been previously well documented in the female Sprague-Dawley rat. However, the preventive effect of melatonin in limiting the frequency of cancer initiation has not been well documented.