Angiotensin Converting Enzyme Inhibitors: Animal Experiments Suggest a New Pharmacological Treatment for Alcohol Abuse in Humans

The prevalence of heavy alcohol consumption is a major problem of increasing proportions throughout the world. Although alcohol sensitizing drugs and more recently serotonin uptake inhibitors are drug interventions with some following, their long term beneficial consequences have yet to be demonstrated. In recent years, we have demonstrated that manipulating activity in the renin-angiotensin system will dramatically alter voluntary alcohol consumption in rats. Based on these findings, the present study evaluated the ability of a class of drugs known as the angiotensin converting enzyme inhibitors to reduce voluntary alcohol drinking in laboratory animals. These drugs prevent the conversion of angiotensin I to angiotensin II. They have been licensed for use in Europe and North America and are indicated in the treatment of hypertension. Our experiments showed that both captopril (Capoten, Squibb) and enalapril (Vasotec, Merck Sharpe & Dohme) can reduce alcohol drinking in both normotensive and hypertensive animals regardless of whether the pattern of intake is in a bout or of a less exaggerated nature. Furthermore, this change in alcohol intake can occur without concomitant changes in blood pressure, plasma renin activity, overall fluid balance, or the distribution and metabolism of alcohol. Taken together these findings suggest that the angiotensin converting enzyme inhibitors should be evaluated in a clinical setting for they may prove to be a useful new treatment or treatment adjunct for alcohol abuse in humans.     

Innervation of the sheep adrenal cortex: an immunohistochemical study with rat corticotrophin-releasing factor antiserum

Using indirect immunohistochemistry and an antiserum raised against rat corticotrophin-releasing factor (CRF) we have outlined an asymmetric network of cells and varicose fibers in sheep adrenal cortex. This network was not associated with the larger splanchnic nerves, but was occasionally found in small bundles or with blood vessels; in most instances fibers were found weaving independently through cortical parenchyma. A plexus of fibers was found in the zona reticularis, with a few fibers ramifying into adjacent medulla. Uni or bipolar cells were found throughout the cortex, with the greatest frequency at the corticomedullary junction; a multipolar-type cell was also found in this area. Staining of varicose structures and most cells was abolished by incubation with excess rat CRF 1-41, but not by ovine CRF or a range of other peptides. Though the immunoreactive species has not as yet been identified, it may thus share homology with sequences present in rat but not ovine CRF.     

APACHE II score and abdominal sepsis. A prospective study

Therapeutic trials for intra-abdominal sepsis require pretreatment stratification; physiologic scoring has been recently proposed for this purpose. We have prospectively tested the validity of one such scoring system, namely, the Acute Physiology and Chronic Health Evaluation (APACHE II). As part of a larger database, we correlated APACHE II scores with mortality in 100 patients hospitalized for generalized peritonitis or abdominal abscess. Use of steroids was recorded because of our suspicion that steroids increase mortality but blunt the physiologic response to sepsis. Thirty-one patients died, including 12 of 19 patients receiving steroids. Stepwise discriminant analysis revealed that the APACHE II score and steroid use were each independently associated with the rate of mortality. We report a prospective validation of pretreatment APACHE II scoring in abdominal sepsis. Steroid use is an independent risk factor.     

Corrosive oesophagitis: an analysis of 50 cases

A total of 50 consecutive patients who were treated in JIPMER Hospital between 1970 and 1981 for corrosive injuries of the oesophagus and stomach were analysed. There were 23 males and 27 females. All but seven presented with dysphagia due to an established stricture. In addition seven of them had associated stricture of the stomach. They were treated with either repeated dilatations or, in selected cases, oesophageal replacement. Perforation of the oesophagus is an important complication associated with oesophageal dilatation indicating the need for oesophageal replacement in multiple or long dense strictures. Results are quite satisfactory with both modalities of treatment. However, oesophageal replacement surgery, performed properly in selected cases, offers a permanent solution to these unfortunate victims.     

Clinical versus ultrasonographic evaluation of scrotal disorders

Clinical and ultrasonographic examinations of scrotal disorders were compared in 166 patients in order to determine their ability to distinguish between those diseases requiring surgery and those requiring clinical follow-up only. Ultrasound examinations were efficient in discriminating between normal and pathological findings. Extra-testicular lesions were readily differentiated from testicular ones. Although both clinical and ultrasonographic examinations had high sensitivity (90%) in detecting testicular cancer, the number of false positive findings was smaller after ultrasound examination. This gave a predictive value of a positive test of 53% after ultrasound examination but only 33% after clinical examination. Ultrasound examination may, therefore, reduce the number of surgical explorations in the scrotum and should be performed in patients with suspected testicular pathology based on history and palpatory findings.     

Chromogenic ionophore-based methods for spectrophotometric assay of sodium and potassium in serum and plasma

We report spectrophotometric methods for quantifying sodium and potassium in serum and plasma without sample pretreatment or solvent-extraction steps. The methods are based on novel chromogenic ionophores characterized by molecular structures highly preorganized for binding, which result in exceptionally high sensitivity and selectivity (negligible responses to sodium at 80 to 200 mmol/L in the potassium assay and to potassium at 0 to 10 mmol/L in the sodium assay). The within-run imprecisions are comparable with those for ion-selective electrodes (for K, 1.0% at 4.5 mmol/L; for Na, 1.1% at 136 mmol/L); the analytical range is 2-10 mmol/L for potassium, 80-170 mmol/L for sodium. The results for greater than 100 patients' samples correlated well with results obtained with ion-selective electrodes (r = 0.99 for K, 0.97 for Na). The ready-to-use aqueous reagents will be available under the trade name of ChromoLyte for use with Technicon's RA family of clinical analyzers.     

Excretory/secretory antigen of Toxocara canis: recognition profiles of polyclonal and larvicidal monoclonal antibodies

Summary Five monoclonal antibodies against the excretory/secretory (E/S) antigen of Toxocara canis were obtained and characterized. Immunoprecipitating activity was demonstrated in an in-vitro micropre-cipitating assay using live T. canis larvae. Their capacity to kill larvae was also shown in an in-vitro assay. Two zones of reactivity were observed in 7.5 and 12.5% SDS-PAGE (177-77 kD, 43-15 kD) of immunoprecipitates of human and mouse positive polyclonal anlisera. The murine monoclonal antibodies showed a common pattern of reactivity with the proteins in the 177-77 kD range.     

Dietary Tryptophan Reverses Alcohol-induced Impairment of Facial Recognition But Not Verbal Recall

The present study demonstrates that alcohol-induced memory impairment can be attenuated by pretreatment with an oral tryptophan supplementation. These results provide support for the role of a brain serotonin deficit in this impairment and highlight the impact a dietary manipulation can have on a complex behavioral process.     

A novel hybridoma antibody (PASE/4LJ) to human prostatic acid phosphatase suitable for immunohistochemistry

A murine monoclonal antibody PASE/4LJ to prostatic acid phosphatase (PAP) was used to immunostain a wide variety of sections of benign and malignant tissues (654 blocks). Non-neoplastic adult and fetal prostatic glands, primary and metastatic prostatic carcinomas, and scattered cells in prostatic and penile urethra were positive. Rat, dog and rabbit prostates were negative. Nine of 400 tumours of non-prostatic origin showed some positivity: 6/36 carcinoids, 1/9 islet cell tumours, 1/55 ovarian adenocarcinomas (serous) and one carcinosarcoma of the lung (epithelial portion). Positive staining was seen in islet cells in 4/5 specimens of normal pancreas, and in 4/9 blocks of normal pancreas surrounding a pancreatic tumour. Loops of Henle, maculae densae, and distal tubules in 10/10 fetal and 2/9 adult kidneys were also positive, with proximal tubules and collecting ducts negative. All other 159 blocks of non-neoplastic adult and fetal tissues were negative. The antibody was also affinity purified from ascitic fluid, and shown not to inhibit the enzyme activity of prostatic acid phosphatase.