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.     

Tetanus in leprosy patients: report of five cases

It has long been noted that tetanus is rare in leprosy patients. Five cases of tetanus are reported in leprosy patients in Addis Ababa, Ethiopia. Although natural immunity to tetanus occurs and this appears to be higher in leprosy patients than in the general population, it is not completely protective. Further research on the relationship between tetanus and leprosy is indicated. Although firm epidemiologic data are lacking, it is prudent to give leprosy patients at least one dose of tetanus toxoid.     

A systematic approach to reconstruction of neglected tears of the patellar tendon. A case report

Neglected tears of the patellar tendon due to loss of active extension remain a difficult therapeutic endeavor. The goals in the approach to this diagnosis include restoration of both structural and functional integrity of the extensor mechanism. A procedure has been developed utilizing Z-shortening of the patellar tendon, Z-lengthening of the quadriceps tendon, and the semitendinosis gracilis as a biologic splint. This technique allows establishment of preoperative goals, including restoration of the muscle-tendon complex in its anatomic position, restoration of quadriceps function, preservation of vascularity of the reconstructed tendon, and splinting of the patellar tendon. This reconstruction allows early mobilization and rehabilitation.     

Adrenal and pseudoadrenal masses: CT and US findings

Computed tomography (CT) is currently the imaging modality of choice for assessing the morphology of the adrenal glands in adult patients. Much useful information can be gained using CT in disease processes which primarily involve one or both of the adrenal glands, such as adenomas, as well as in entities which secondarily affect the adrenals, such as pituitary or metastatic disease. The size and configuration of the glands can be readily determined, and masses may be detected. We discuss CT of normal and abnormal adrenal glands with sonographic (US) and pathological correlation, when available. Entities which may mimic adrenal abnormalities are emphasized. Relative advantages of US over CT in the pediatric patient are discussed.     

Evidence that the Receptor for Soluble CD14:LPS Complexes may not be the Putative Signal-Transducing Molecule Associated with Membrane-Bound CD14

Membrane-bound CD14 acts as a receptor for lipopolysaccharide (LPS) on monocytes/macrophages and neutrophils. Studies have suggested that the activation of monocytes/macrophages by the binding of LPS to membrane-bound CD14 may require the association of a signal-transducing molecule with membrane-bound CD14. The observation that non-CD14 expressing cells, such as endothelial cells, can nevertheless be activated by a complex of LPS and a soluble form of CD14 (sCD14) suggests that the receptor for this complex may be identical to the signal transducing molecule associated with membrane-bound CD14. The studies described show that two CD14-specific MoAb are able to block the LPS-induced activation of endothelial cells but do not affect the response of monocytes to LPS. This suggests that the interaction of the sCD14:LPS complex with endothelial cells is distinct from the interaction of membrane-bound CD14 with its putative signal-transducing molecule.     

The effect of palytoxin on neuromuscular junctions in the anococcygeus muscle of the rat

Palytoxin, a highly toxic natural product isolated from zoanthids of the genus Palythoa, is accumulated by a wide range of fishes and marine invertebrates used as food in the Indo-Pacific. It is responsible for many incidents of human morbidity and mortality. The toxin is a potent smooth muscle spasmogen. The cause of the contraction of smooth muscle is unclear, but recent work strongly suggests that it is primarily initiated by the release of neurotransmitters from the motor innervation of the smooth muscle. We show here that palytoxin caused the swelling of the muscle cells and some internal organelles of the anococcygeus muscle of the rat, but no substantial structural damage to the tissue. Axons and Schwann cells were also swollen but the most dramatic feature was the depletion of synaptic vesicles from putative release sites in the axons. Some axons were physically damaged following exposure to the toxin, but this was relatively uncommon (<10% of all axons studied). In the majority of axons there was no damage to nerve terminal membranes, but there was damage to mitochondria. The depletion of vesicles involved all types – clear, dense-cored, large and small. Our observations and pharmacological data gathered elsewhere, provide a neuropathological basis for the spasmogenic activity of palytoxin.