Controlled-release products for the control of the estrus cycle in cattle, sheep, goats, deer, pigs, and horses

This paper describes the estrus cycles of a number of livestock breeds and reviews the controlled-release drug delivery systems that are currently available for the purpose of controlled breeding. The bovine estrus cycle is reviewed in detail, and the estrus cycles of other species are described in a manner that highlights similarities and differences between species. Pertinent formulation and pharmacokinetic information about current drug delivery systems is presented and discussed, and recent advances in this area are also described.     

A sonographically guided technique for central venous access

OBJECTIVE: The internal jugular vein (IJV) is an important access to the central venous system. We compared sonographically guided technique with the traditional anatomic landmark technique for IJV catheterization. SUBJECTS AND METHODS: In a prospective randomized trial, 100 patients underwent routine catheterization of the IJV (50 patients in the sonography group and 50 patients in the anatomic landmark group). Access time, failure rates, and complication rates were evaluated. In addition, the physicians' number of years of experience with catheter insertion was recorded. RESULTS: Access time was markedly shorter with the sonographically guided technique (mean, 15.2 sec; range, 8-76 sec) than with the anatomic landmark technique (mean, 51.4 sec; range, 3-820 sec) (p = .001). The failure rate was significantly lower with the sonographically guided technique (p = .002). Complications were fewer with the sonographically guided technique (neck hematoma, 2% versus 10%; plexus irritation, 4% versus 6%; carotid artery puncture, 0% versus 12%). We found that the number of years of postgraduate clinical training was greater in the group of physicians using the anatomic landmark technique. CONCLUSION: The sonographically guided technique is associated with less risk and less inconvenience for patients, especially critically ill patients, for whom the technique provides fast, safe, and easy IJV catheterization.     

Drug rationalization: now for the hard part

In 1995 a national drug policy was finalized in Nepal. The authors outline the measures that were recommended for its implementation and the activities that have so far been undertaken. Much remains to be done, most notably in assisting, coordinating and supervising these activities.     

Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors

Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.     

A novel cyclic adenosine monophosphate analog induces hypercalcemia via production of 1,25-dihydroxyvitamin D in patients with solid tumors

The treatment of cancer patients with conventional chemotherapy is sometimes associated with severe systemic toxicity and only a minimal survival benefit. Because of this, new less toxic and more efficacious treatments have been sought. 8-Chloro-cAMP (8-Cl-cAMP) is one of a new generation of anticancer drugs that act at the level of signal transduction. In preclinical models, 8-Cl-cAMP modulates protein kinase A (PKA) leading to growth inhibition and increased differentiation of cancer cells. 8-Cl-cAMP was given to 16 patients with advanced cancer as an infusion via an indwelling subclavian venous catheter. We showed that 8-Cl-cAMP had a parathyroid hormone-like effect leading to increased synthesis of renal 1,25-dihydroxyvitamin D [up to 14 times the baseline value, median 3.6 times; P = 0.00001 (Student's paired t test)]. This produced the dose-limiting toxicity of reversible hypercalcemia that could not be controlled by the administration of either pamidronate or dexamethasone. The treatment was otherwise well tolerated, and other cAMP-dependent pathways (cortisol and TSH) were not affected, emphasizing the marked differences between organs in their sensitivity to this cAMP analog. Our results have shown that 8-Cl-cAMP is biologically active, and it is feasible that if the hypercalcemia can be controlled, then this drug may have a role as a single agent, or as a short infusion between cycles of chemotherapy.     

Disposition of aerosolized liposomal amphotericin B

Amphotericin B (AmB) is an important drug for the treatment of fungal infection, but toxicity limits the lung tissue doses which may be achieved through intravenous administration. Although incorporation of AmB in liposomes reduces these effects and increases the therapeutic index for intravenous administration, targeted delivery to lung tissues via inhaled liposomal AmB aerosol may be a more effective approach. Aerosolization of liposomal amphotericin B targets the lungs, the organs first infested by many fungi. Development of optimal aerosolized liposomal AmB therapies requires a better understanding of the effect that liposome surface charge has on lung clearance kinetics. In this work we evaluated the clearance kinetics and organ distribution of inhaled liposomal AmB in male Balb/C mice. Mice were exposed via nose only to AmB-containing liposomal aerosols having positive, negative, or neutral surface charge characteristics. The formulations were aerosolized using a Collison nebulizer. Groups of animals were euthanized at predetermined times and the lungs and other organs were analyzed for AmB. AmB was not detected in serum and other organs such as kidneys, liver, and brain. The disposition of neutral and positive liposomal amphotericin B in lungs followed biexponential kinetics. The alpha and beta phase half-lives for positive liposomes were 1.3 and 15.1 days, respectively, and 2.3 and 22 days for neutral liposomes. AmB delivered via negative liposomes exhibited monoexponential clearance with a half-life of 4.5 days. These results suggest that toxic side effects in nontarget tissues are minimal and may indicate a potential for long term protection against fungal infections.     

Chemical Composition and Physical Properties of High Oleic Safflower Oils (Carthamus tinctorius,Var. CW88-OL and CW99-OL)

Chemical composition and physical properties of CW88‐OL and CW99‐OL cultivars of high oleic safflower seeds and their hexane‐extracted oils were determined. Dry‐based seed composition of CW88‐OL and CW99‐OL was: moisture = 4.29 and 4.23 %, oil = 42.29 and 46.44 %, Crude protein = 20.94 and 16.41 %, neutral detergent fiber = 28.11 and 28.49 %, ash = 1.55 and 2.01 %, phosphorus content = 2033 and 3995 mg/kg, respectively. Major fatty acids in oils were ~78 % oleic (O), ~13 % linoleic (L), ~5 % palmitic (P) and ~2 % stearic (St) acids, for both cultivars. The main triacylglycerols were OOO (~50 %), OOL (~20 %), SOL + OPO (~10 %), and LLP (~5 %). The oil composition of CW88‐OL and CW99‐OL in main minor components was: α‐tocopherol = 582 and 551 mg/kg, total sterols = 3996 and 3362 mg/kg, phospholipids = 22 and 21 mg/kg and wax content = 70 and 74 mg/kg. For both cultivars, density and viscosity of the oils between 25 and 55 °C varied from 903.4 to 912.6 kg/m³ and 63 to 23 mPa.s showing linear and exponential behaviors, respectively. The refractive index was 1.4694. The CIELab color parameters were: 89.69 and 89.53 (L*), ?3.72 and ?3.07 (a*), and 47.28 and 47.78 (b*) (CW88‐OL and CW99‐OL, respectively). Thus, the high oil content of the seeds and nutritional quality of the oil accompanied by low levels of waxes and phospholipids makes the cultivars studied promising for producers and consumers.     

Relation Between Oxidative Stability and Composition in Argentinian Olive Oils

The relation between oxidative stability and composition in 58 virgin olive oils from different cultivars and Argentinian regions was studied over four harvest years. The oxidative stability of the oils was assessed using the OSI index (110 °C, 20 L/h air flow). A multiple linear regression model is proposed using OSI values as the dependent variable (multiple R = 0.933, p = 1 × 10⁻¹⁵), with positive contributions of the independent variables: fatty acid composition [oleic acid/(linoleic acid + linolenic acid), 55.3%, p = 1 × 10⁻¹⁵], total polyphenols (24.1%, p = 1.8 × 10⁻⁹), carotenes (4.8%, p = 6.1 × 10⁻⁵), β-tocopherol (1.9%, 6.0 × 10⁻³) and other compounds (13.9%). Highly significant correlation was observed between oxidative stability indexes estimated by the compositional model and those experimentally determined by Rancimat method (b = 0.981, R = 0.924). Chlorophylls and Δ-5-avenasterol contributions to the model were non-significant when variables related with fatty acids and polyphenols were included. The results suggest that the fatty acid composition and the polyphenol content are the main factors that affect the oxidative stability of olive oils. The proposed model allows the estimation of the oxidative stability in olive oils independently of the cultivar. The model was obtained also taking into account samples that lie out of the international legal limits in some compositional values due to natural variations.