Clay Sols versus Clay Gels: Biological Activities Compared.

Clay gels were prepared by extrusion of sodium-Wyoming bentonite pastes through a small orifice. Clay sols were prepared from the gels by rapping on the laboratory bench for disturbance. Lettuce seeds germinated faster, microbes generated more heat, and corn seedlings absorbed more (22)Na in the sols than in the gels. These differences in biological activity are attributable to changes in water properties and ion activities that accompany transformation from gelsol.

Sewage sludge as a source of cadmium in soil-plant-animal systems.

The objective of this presentation is to relate the abundance and mobility of Cd in components of terrestrial ecosystems with implications for land utilization of sewage sludge. The uptake of Cd by crop plants is a function of the quantity of the element in the soil plus other soil factors affecting the Cd ion activity or electrochemical potential at the plant root surface. The natural abundance of Cd in soils has been reported as 0.5 mug/g which is higher than the background level of 0.2 mug/g found in soils studied in Pennsylvania. Experimental results indicate that the plant availability of Cd increases with each soil addition. While the plant availability of Cd is decreased by liming to increase soil pH, it has not been possible to add Cd salts or sewage sludge Cd without significantly increasing plant uptake. Field studies have shown that land application of sewage sludge can be expected to increase the Cd concentration of corn leaves from a range of 0.05-0.1 mug/g to 1-3 mug/g. Two years after the last application of sludge which added up to 10 ppm Cd to the surface soil, corn grain, sorghum grain, wheat grain, and potatoes showed a 10- to 15-fold increase in Cd over background levels. Studies were conducted with chicks, laying hens, and meadow voles (Microtus Pennsylvanias) to assess the impact of this increase in plant Cd upon the food chain. Corn and sorghum plants were grown on soils with either inorganic or sludge fertilizer for the purpose of producing herbage for use in feeding trials with meadow voles. Eight diets and a synthetic control diet were formulated to study the effect of source (plant vs. inorganic) of Cd on tissue accumulation. Significant accumulation of Cd occurred in kidney and liver, but not muscle, of voles fed diets containing sludge fertilized corn (1.09 mug/g) or sludge fertilized sorghum (2.76 mug/g). The source of Cd had little influence on tissue accumulation. In studies with broiler chicks and laying hens, natural diets containing 0.2 ppm Cd were supplemented with 3 ppm of this element. As with the meadow voles, Cd readily accumulated in liver and kidney. Although the results were not statistically significant, 3 ppm dietary Cd doubled muscle Cd content. There was no transfer of Cd to egg in a long term (12 month) experiment with laying hens. Soil management programs have been developed to maintain animal dietary levels of Cd at less than 1.0 mug/g from the use of sewage sludge on land in Pennsylvania. However, it is concluded that this level over time may cause a significant accumulation of Cd in animal tissues. Interpretation of these results in relation to those for human intake of Cd and the long range health effects of Cd is required for the proper monitoring of sewage sludge applications on land used for production of crops which enter the food chain.

Esomeprazole magnesium (Nexium).

Esomeprazole, the S-isomer of omeprazole, is a new proton pump inhibitor. Esomeprazole provides better control of intragastric pH than omeprazole. It is more effective in treating erosive esophagitis in patients with GERD than omeprazole. Esomeprazole can maintain the healing of erosive esophagitis when used daily or on demand. It is also effective for the eradication of Helicobacter pylori infections. The incidence and type of adverse events associated with esomeprazole therapy are infrequent and likely to be similar to omeprazole.

Pegylated interferons.

Interferon therapy for chronic hepatitis C is not a cure, but it is able to decrease the viral load and may decrease the risk of complications (e.g., cirrhosis, liver failure, liver cancer). Pegylation of the interferon increases the amount of time the interferon remains in the body by increasing the size of the interferon molecule. Increasing molecule size slows the absorption, prolongs the half-life, and decreases the rate of interferon clearance. Thus the duration of biological activity is increased with pegylated interferon over nonpegylated interferon. The peginterferon alfa products offer an advantage over nonpegylated interferon alfa products because of less frequent administration. Tolerability of the pegylated interferons is comparable to the nonpegylated formulations. Monotherapy with these agents produces a better response in some patients than monotherapy with the nonpegylated formulation. Combination therapy with ribavirin is more effective than monotherapy. Studies comparing peginterferon alfa-2b and peginterferon alfa-2a in the treatment of chronic hepatitis C have not been performed.

Budesonide modified-release capsules.

Budesonide modified-release capsule is an effective form of therapy for the treatment of Crohn's disease located in the distal ileum, ileocecal region, and ascending colon. Because some of the benefit of budesonide therapy results from local effects, this agent will not be very effective in the treatment of patients with extensive colitis or left-side colitis. Budesonide is equal to less effective than prednisolone or prednisone therapy in the treatment of active Crohn's disease, but is associated with fewer glucocorticoids adverse reactions.

Tegaserod for the treatment of constipation-predominant irritable bowel syndrome.

Tegaserod, a potent, partial serotonin 4 receptor (5-HT4) agonist, is an effective agent for the treatment of females with constipation-predominant irritable bowel syndrome. Tegaserod enhances gastric motility, stimulates peristaltic reflux and intestinal secretion, inhibits visceral sensitivity, and/or shortens colonic transit time. This agent may help women who have failed to respond to diet and exercise, laxatives, and other forms of therapy. The optimal dose of tegaserod is 6 mg twice daily and results in decreased number of days per month with pain, bloating, and days without bowel movements. Tegaserod is less effective in males than females in the treatment of constipation-predominant irritable bowel syndrome. Tegaserod is well tolerated. Diarrhea is the most frequent adverse effect. The diarrhea tends to occur most frequently during the first few months of therapy and decreases with continued administration.

Cerebrovascular permeability and delivery of gentamicin to normal brain and experimental brain abscess in rats.

Antibiotics vary widely in their ability to penetrate the blood-brain barrier. In studies of 70 rats, the permeability of the normal blood-brain barrier to gentamicin was shown to be poor. In experimental brain abscesses, during the cerebritic stage of development, the penetration of intravenous antibiotics was increased compared to normal brain but was very inconsistent. Antibiotic delivery to brain abscess was not significantly altered with the administration of high-dose steroids, but the macrophage and glial response was markedly decreased with high-dose steroid therapy. Reversible osmotic blood-brain barrier modification with mannitol increased the delivery of gentamicin both to brain abscess and to the surrounding brain. It also resulted in more consistent tissue drug levels. The clinical implications of these studies suggest that, because of the inconsistent delivery of gentamicin to brain abscess, the therapeutic efficacy of medical management alone may be quite variable. This mode of therapy could possibly increase the efficacy of medical management of brain abscesses, especially in patients with multiple or surgically inaccessible brain abscesses.

Vitamin and mineral supplementation in patients with diabetes mellitus.

Most patients with diabetes generally do not require routine vitamin and mineral supplementation, just like the rest of the population. However, based on the published medical literature, it would appear that some degree of supplementation with certain vitamins (eg, vitamins C and E) and minerals (eg, magnesium) may be worthwhile and become more commonly recommended in the future. The role of vitamins and minerals in controlling blood glucose levels in the patients with diabetes also is discussed.

High-frequency hearing loss in male farmers of Missouri.

Farmers are exposed to noise that is potentially hazardous to hearing. We measured the hearing of 161 male farmers and 75 male nonfarmers at the 1979 Missouri Farmers Association Agri-Fair and compared it with the hearing of 129 office workers from central Missouri. Fixed-level screening tests were conducted in both ears at three stimulus frequencies: 1000 and 2000 hertz at 20 decibels hearing level and 4000 hertz at 25 decibels hearing level. Audiometers were calibrated in accordance with the ANSI-1969 standard. The results show that farmers are at risk for hearing loss at 2000 and 4000 hertz when compared with office workers. The prevalence of hearing loss was greater for farmers at both frequencies in every decade age group from 25 to 64 years. Using screening failure at 2000 and 4000 hertz in both ears as a criterion for a loss that would affect communication ability, we found that the failure rate was 16.8 percent for farmers and 6.2 percent for office workers. As other investigators have found, the prevalence of high-frequency hearing loss in male nonfarmers who associate with farmers was nearly as great as for farmers.

Direct measurement of unfractionated heparin using a biochemical assay.

A number of investigations have noted that functional biological assays for heparin are not always reliable and may not reflect the actual biochemical level of heparin in patients receiving anticoagulant therapy. This creates the possibility that patients receiving anticoagulant treatment may have an excess or deficiency of circulating levels of heparin. To address this problem, we have developed a direct biochemical measurement of heparin. The heparin assay uses fluorophore-assisted carbohydrate electrophoresis (FACE) to directly measure the predominate disaccharide of unfractionated heparin. In this study, unfractionated heparin was measured in vitro throughout a wide range of heparin concentrations in plasma. Seven in vivo pharmacokinetic studies in five normal subjects given 3,000 USP units of unfractionated heparin intravenously showed a three-phase elimination process with higher peak plasma levels and shorter elimination times than predicted from previous studies. At these doses, heparin is largely eliminated intact through urinary excretion. Body weight has a significant effect on heparin kinetics. When we compared the direct biochemical assay with two biological clotting assays, we found the latter can overestimate biochemical heparin concentrations. The FACE assay, due to its sensitivity, is also able to measure circulating levels of endogenous heparin in plasma and urine. Direct heparin measurement using the FACE technique is practical and useful for studies of the correlation of biochemical and biological activities.

Effects of dietary cadmium chloride throughout gestation on blood and tissue metabolites of primigravid and neonatal dairy cattle.

Thirty-six postpubertal Holstein heifers were allocated to three groups and fed the same diet, which differed only in the concentration of Cd: control group (.25 ppm of Cd), low-Cd group (1 ppm of Cd), and high-Cd group (5 ppm of Cd). Cadmium was supplemented to the low-Cd and high-Cd groups using CdCl2. Liver, kidney cortex, and abdominal muscle were biopsied for mineral analysis from one-half of the heifers of each group before Cd supplementation and again from the same animals within 5 d after parturition, 394 d later. Blood, liver, and muscle were collected from each calf within 5 h after birth. In the dam, 5 ppm of dietary Cd caused a 62-, 27-, and 4-fold increase in Cd of the kidney, liver, and muscle, respectively; kidney Zn and Fe increased (76%) and decreased (33%), respectively, whereas the serum Cu was reduced (31%). Liver Cu was reduced to 40 and 17% by dietary Cd of 1 and 5 ppm, respectively, in the dams. Calves from dams consuming 5 ppm of Cd had a 29 and 43% reduction in liver Cu and Zn, respectively. In these same calves, packed cell volume, hemoglobin concentration, and serum Cu were decreased by 17, 18, and 25%, respectively, whereas serum Zn was increased (55%). Serum sodium and potassium were reduced by 4 and 13%, respectively, and blood urea nitrogen was increased by 63% in calves from dams consuming 5 ppm of Cd. Feeding primigravid dairy cattle up to 5 ppm of Cd as CdCl2 throughout gestation did not influence the concentration of Cd in the neonate but caused reductions in liver Cu and Zn; teratogenesis was not apparent.

Effects of long-term dietary cadmium chloride on tissue, milk, and urine mineral concentrations of lactating dairy cows.

The effects of long-term consumption of 1 and 5 ppm of Cd on Cd, Cu, Fe, and Zn concentrations in milk and a variety of tissues of first-lactation dairy cows was investigated. Thirty-six Holstein heifers were allocated to three groups and fed similar diets differing only in the concentration of Cd (.25, 1, and 5 ppm) for a 394-d period before calving. One- and 5-ppm Cd concentrations were achieved using CdCl2. Liver, kidney cortex, and muscle were biopsied from one-half of the heifers of each group before Cd supplementation and again from the same heifers within 5 d after parturition. Colostrum and milk were sampled throughout the 150 d of lactation. Urine was sampled after an average of 450 d of Cd exposure. At slaughter (after an average of 554 d), 11 tissues were sampled from 12 cows representing all treatment groups. During the first 394 d, Cd accumulated in kidney and liver with increasing dietary concentrations of Cd but did not further increase by 554 d. However, by 554 d Cd had also accumulated in the adrenal glands, ovaries, spleen, and uteri of cows consuming 5 ppm of Cd. Dietary Cd did not influence the concentration of Cd, Cu, Fe, or Zn in colostrum or milk. However, urine pH, Zn, and K were lower in cows consuming 5 ppm of Cd. Liver Cu was reduced by 1 and 5 ppm of Cd at both 394 and 554 d.(ABSTRACT TRUNCATED AT 250 WORDS)

Force spectroscopy of hepatocytic extracellular matrix components.

We present atomic force microscopy and force spectroscopy data of live hepatocytes (HEPG2/C3A liver cell line) grown in Eagle's Minimum Essential Medium, a complex solution of salts and amino acids commonly used for cell culture. Contact-mode imaging and force spectroscopy of this system allowed correlation of cell morphology and extracellular matrix (ECM) properties with substrate properties. Force spectroscopy analysis of cellular "footprints" indicated that the cells secrete large polymers (e.g., 3.5mum contour length and estimated MW 1000kDa) onto their substrate surface. Although definitive identification of the polymers has not yet been achieved, fluorescent-labeled antibody staining has specified the presence of ECM proteins such as collagen and laminin in the cellular footprints. The stretched polymers appear to be much larger than single molecules of known ECM components, such as collagen and heparan sulfate proteoglycan, thus suggesting that the cells create larger entangled, macromolecular structures from smaller components. There is strong evidence which suggests that the composition of the ECM is greatly influenced by the hydrophobicity of the substrate surface, with preferential production and/or adsorption of larger macromolecules on hydrophobic surfaces.

Therapeutic advances in the prevention of hepatitis B: yeast-derived recombinant hepatitis B vaccines.

Viral hepatitis is second to gonorrhea as the most commonly reported infectious disease in the US. Hepatitis B accounts for the majority of viral hepatitis cases. Fortunately, the disease is self-limiting and frequently resolves completely with minimal complications; however, a significant number of individuals may experience long-term sequelae. Research utilizing genetic engineering has led to the development of yeast-derived recombinant DNA (YDR) hepatitis vaccines--a significant advancement in the control and prevention of hepatitis B. The recombinant process allows production of unlimited quantities of vaccine at considerably lower cost and without the potential threat of blood-borne illness. Clinical trials in various high-risk populations have demonstrated the effectiveness and safety of YDR vaccines. However, questions regarding optimal regimen and the need for periodic revaccination remain unanswered. Persons at risk should be adequately vaccinated against hepatitis B.

Pentoxifylline: a new agent for intermittent claudication.

Pentoxifylline is approved by the Food and Drug Administration for the treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs. It is not a substitute for surgical bypass or removal of arterial obstructions, but will improve function and symptoms of the disease state. The mechanism by which pentoxifylline works is not well known, but appears to be related to erythrocyte adenosine triphosphate (ATP) concentrations and the phosphorylation of erythrocyte membrane proteins, both mechanisms resulting in an improvement in erythrocyte flexibility. Efficacy studies indicate that pentoxifylline is significantly more effective than placebo or nylidrin therapy. Adverse reactions are mainly of the gastrointestinal type and are minimized by the use of a controlled-release dosage form.