Dodecyl N,N-Dimethylamino Acetate and Azone Enhance Drug Penetration Across Human,Snake, and Rabbit Skin

The effectiveness of the penetration enhancers, dodecyl N, N-dimethylamino acetate (DDAA) and Azone, on pretreated human epidermis for the permeation of model drugs, indomethacin, 5-fluorouracil, and propranolol-HCl, was studied in in vitro diffusion cells. Snakeskin (Elaphe obsoleta) and rabbit pinna skin were compared as possible models for human skin. The drug concentrations were analyzed by HPLC. With all skins and all model drugs, DDAA increased drug permeability at least as well as Azone, and in most cases it was a more effective permeation enhancer. The relative permeation improvements in human skin, snakeskin, and rabbit skin were 10- to 20-, 5- to 50-, and 20- to 120-fold, respectively. Tritiated water served as an indicator of skin condition. Its penetration in the skin samples was independent of the drugs used, and both penetration enhancers significantly increased the flux of tritiated water through all skins. Thus, DDAA and Azone significantly increased the permeation of lipophilic and hydrophilic model compounds. Rabbit pinna skin was a poor model for human skin in vitro, while snakeskin was much closer to human skin in terms of transdermal permeability. In most cases drug permeability decreased in the order rabbit human > or < snake.     

Polycyclic aromatic hydrocarbon (PAH) metabolizing enzyme activities in human lung,and their inducibility by exposure to naphthalene,phenanthrene, pyrene,chrysene, and benzo(<Emphasis Type="Italic">a</Emphasis>)pyrene as shown in the rat lung and liver

In order to survey changes and activities in the polycyclic aromatic hydrocarbon (PAH)-metabolizing enzymes implicated in lung cancer susceptibility studies, we investigated enzyme induction by 2–5-ring-sized ‘biomarker’ PAHs in rat liver and lung, and the activities in five human lung specimens. Naphthalene, phenanthrene, pyrene, chrysene, and benzo[a]pyrene (BaP) were administered to rats for 3 days (25–128 mg/kg/day) and the responses compared with those of model inducers. PAH treatment increased the CYP1A-catalyzed activity of pyrene 1-hydroxylation and 7-ethoxyresorufin O-deethylation in rat liver by up to 28- and 279-fold, and in rat lung by up to 22- and 51-fold, respectively. 1-Naphthol (hUGT1A6), 1-hydroxypyrene (hUGT1A6/1A9), and entacapone (hUGT1A9) are markers of PAH-glucuronidating human uridine diphosphate-glucuronosyltransferases (UGT). These activities increased up to 6.4-fold in rat liver and up to 1.9-fold in rat lung. NADPH:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase activities increased up to 5.3- and 1.6-fold (liver), and up to 4.4- and 1.4-fold (lung), respectively. CYP1A showed the best liver-to-lung relationship (R ² = 0.90). The inducing efficiency by PAHs differed extensively: control ≤ naphthalene < phenanthrene, pyrene << chrysene < BaP. In human lung (non-smokers), the marker activities of CYP1A1, UGT1A6/1A9, and NQO1 were lower than those in rat lung. Epoxide hydrolase activity was 1,000-fold higher than the pulmonary CYP1A1 activities. Human UGT and NQO1 displayed large variations (>60-fold), many times greater than the experimental (inducible/constitutive) variation in the rat. Kinetics of 1-hydroxypyrene glucuronidation showed two low-K _m forms both in rat and human lung. Since the 2–4-ring PAHs (major constituents) were poor enzyme inducers, it appears that the PAH-metabolizing pathways are mainly induced by BaP-type minor constituents. Gene–environmental interactions which magnify polymorphic variability in pulmonary bioactivation/detoxification capacity probably play a key role in individual susceptibility to (or protection against) chemically induced lung cancer. Hence, human exposure to PAH mixtures with high content of BaP-type hydrocarbons confers a potentially higher health risk than PAH mixtures with low content of procarcinogens.     

Factors related to coping with physical and instrumental activities of daily living among people born in 1904–1923

Functional ability is affected by a number of different factors, including biological ageing, illness, and living environment. This study was concerned with the connections of functional ability with mood and cognitive capacity in elderly individuals. It forms part of a cross-sectional study which was carried out in 1988, involving two random samples of 800 non-institutionalized persons born in 1904–1913 and 1914–1923. Functional ability tests included 18 questions; eight concerned coping with physical activities of daily living (PADL) and 10 instrumental activities of daily living (IADL). Depressive symptoms and cognitive capacity were examined by tests. In addition, there was a set of questions concerning health status and socioeconomic situation. Regression models (LISREL) were used to identify factors associated with PADL and IADL activities. In the younger age group, 68% of the men and 65% of the women had no difficulty in coping with PADL activities. The figures for the older group were 58% and 37%, respectively. Difficulties were reported more frequently with IADL activities. In the older age group 17% of the men and 10% of the women coped with no difficulty. In all activities difficulties tended to increase with age, and more so among women than men. The explanatory factors that emerged from the regression models as most significant were the number of chronic illnesses, the number of depressive symptoms and cognitive capacity.     

New automated physical phantom for renography.

Physical phantoms have been used to test the diagnostic proficiency of nuclear medicine professionals and the accuracy of their equipment in external quality assurance surveys. No dynamic renal phantoms are commercially available. A new renal phantom, presented in this paper, was constructed and patented in the United States. METHODS: The organs to be simulated by the phantom were in the form of containers filled with radioactive solution, and the device further comprised movable steel and lead plates between the containers and the gamma-camera. The detectable radiation was regulated in accordance with automated computer-controlled step motors to move the attenuators to simulate a given patient situation. The reproducibility of the phantom measurements was defined as a coefficient of variation. Four different kidney-function simulations were repeated 3 times, and 6 parameters were compared. RESULTS: The average root mean square deviation of the coefficient of variation was 6.7% for the perfusion integral, 1.3% for time to reach the maximum activity, 19.7% for mean transit time, 3.3% for function (Patlak [%]), 1.0% for outflow index (%), and 6.5% for time to reach the half-activity from maximum. CONCLUSION: With this phantom, the true values of most parameters measured are well known; it closely approaches true extraction, washout, and attenuation properties and curves, and the images produced are similar to those of patient studies. Compared with the first manual version, this new automated phantom is easy to use. Any desired clinical situation can be programmed. It is a promising tool for quality assurance and calibration of renography.     

Use of drugs by non-institutionalized urban Finns born in 1904-1923 and the association of drug use with mood and self-rated health.

The purpose of this study was to examine the use of drugs by elderly people and to investigate its associations with various other factors. Random sampling was used to select 800 interviewees born in 1904-13 and a further 800 born in 1914-23. The average number of prescribed drugs per person was 2.2. Women used a greater number of prescribed drugs than did men; and this difference increased with age. The use of vitamins and trace elements seemed to decline with increasing age. Among women a significant association between the use of prescribed drugs and depressive symptoms was found. Women in the older age group used prescribed drugs more often than women in the younger age group. One fifth of the subjects had a greater number of drugs in simultaneous use than is generally recommended. It seems that, especially among elderly women, depression often remains undiagnosed and treatments are chiefly provided for the associated symptoms.     

Congenital choledochal cyst opening into the intraduodenal part of the common bile duct and complicated by cystolithiasis and acute pancreatitis

The aim of this report was to present an interesting surgically treated patient having a rare type III choledochal cyst with peculiar clinical course. Anatomically the cyst was a diverticulum of ampulla Vater. It contained stones and was lined by duodenal mucosa. At admission the patient had an actual, severe pancreatitis simulating appendicitis. Two laparotomies were done before the final successful cystoduodenostomy. Ultrasonography was the most illustrative and reliable preoperative diagnostic method.     

Experimental cerebrovascular disorders: Effects of papaverine and theophylline

This study investigated the role of endogenous adenosine in eliciting the increases in cerebrospinal fluid cyclic adenosine 3′,5′-monophosphate concentrations induced by experimental cerebrovascular disorders in rabbits. One group of animals received theophylline, an adenosine antagonist, and another group papaverine, and inhibitor of adenosine uptake, for 7 successive days before the operations. control animals were similarly pretreated with physiologic saline. Papaverine significantly augmented the acute increase in cyclic cAMP concentration of cerebrospinal fluid whereas theophylline leveled off this elevation response. The present findings apparently imply an important role of adenosine in leading to accumulation of cyclic AMP in the cerebrospinal fluid after the experimental cerebrovascular impairment. A further assessment of various adenosine antagonists in the treatment of such disorders seems to be indicated.     

Laser vascular welding—How does it work?

This study evaluated the histology and electron microscopy of four samples of 2 cm long venotomles and artery-vein anastomoses formed in canine femoral arteries and veins using the argon laser (0.5 W power, 1 800 J/cm², 4 min exposure/1 cm length of anastomosis). Welds were continuously irrigated with saline during the procedure to limit maximal temperatures to 44.2±1.6°C (mean±SD), and the specimens were removed immediately following fusion and preserved for examination. Histologic and electron microscopic examination of different areas of the welds revealed various mechanisms of fusion including a) apposition of denatured collagen and elastin in the media and adventitia; b) bonding of veln medial collagen and elastin to the internal elastic membrane of the artery; and c) fusion consisting of a coagulum of platelets and fibrin depending on the allgnment and apposition of the vessel edges. This study demonstrates that vascular tissue fusion by the argon laser occurs by various mechanisms. Future experiments should delineate which types of seal produce the optimal strength at the time of fusion, and enhance longterm healing. Presented at the 1986 Southern California Vascular Surgical Society meeting, September 26–28, 1986, Long Beach, California. Supported by Grants HL-32622, GM-288833, AM-28450 and AM-35297 from USPHS, National Institutes of Health.     

Necrotizing colitis

Seven patients with necrotizing colitis treated surgically are presented. Old age, cardiac failure, arteriosclerosis, mental disease, constipation, ischemic colonic stricture, bronchial asthma, rheumatoid arthritis, and previous radiation therapy are suggested as predisposing factors. Symptoms and signs were those of an acute abdominal catastrophe with peritonitis and peripheral collapse. The incorrect preliminary and operative diagnoses in this series point to a lack of familiarity with this disease entity.After necessary resuscitation, laparotomy was immediately performed, and an enormously distended colon was found resulting from massive necrosis in six patients and imminent necrosis in one. No evidence of occlusion of the blood supply of the mesenteric vessels was seen. The entire colon was involved in two cases. The ischemic cause was obvious on the basis of clinical, radiologic, operative, and/or pathologic appearance of the lesions.Five patients survived. Wide excision of the involved colon and delayed reanastomosis are recommended in the surgical treatment.