Feedlot therapeutics

This article discusses therapeutic approaches to conditions commonly encountered in feedlots. Challenges discussed include bovine respiratory complex, tracheal edema, atypical interstitial pneumonia, footrot, toe abscesses, mycoplasma arthritis, cardiovascular disease, lactic acidosis, bloat, coccidiosis, central nervous system diseases, abscesses and cellulitis, pregnancy management and abortion, and ocular disease.     

Advanced therapeutics program

It has been a very exciting year for the advanced therapeutics team. We have seen our program become a reality, having successfully transplanted our first patients early this spring. The clinical and laboratory parts of our team work well together, never losing sight of our common goal-providing a state-of-the-art program for our patient population. The role of primary nurse coordinator remains a challenging one as the technological advancements in science and medicine continually provide us with the knowledge to make changes and improvements in our care.     

Pharmacology of nebivolol

Nebivolol is a new selective beta 1-adrenergic blocking agent, that possesses a peculiar pharmacodynamic profile and an original chemical structure, by which it differs from traditional beta 1-blockers. Nebivolol is a racemic mixture of two enantiomers in equal ratios. It is endowed with a highly selective beta 1-blocking activity, and does not show an intrinsic sympathomimetic activity. Nebivolol is endowed with peripheral vasodilating properties mediated by the modulation of the endogenous production of nitric oxide. It does not significantly decrease airway conductance compared with atenolol and propranolol. Nebivolol does not compromise the left ventricular function, but it may increase stroke volume, and does not reduce heart inotropism during exertion. Nebivolol is quite safe and is well tolerated, also when compared to traditional beta-blockers. The most common adverse effects are dizziness, headache and fatigue. Owing to its combined dual mechanism of action, nebivolol leads to a unique haemodynamic and therapeutic profile by which it may be advantageous in essential hypertension, ischaemic heart disease and congestive heart failure.     

Tuberculosis. Current therapeutics

Due to the constant decline in incidence up to the mid eighties, eradication of tuberculosis appeared to be an attainable objective in developed countries. Since then multiple factors (HIV epidemic, poor social conditions in certain unfavored areas, population migrations, urbanization) have led to an increased frequency, making an excellent knowledge of tuberculosis a priority for all physicians. Multi-resistant mycobacteria have also made their appearance leading to numerous clinical and experimental studies which provide new insights into the correct management of patients with tuberculosis. Despite these recent changes, the classical treatment for tuberculosis remains the same in most cases, allowing nearly-certain cure when applied correctly in patients infected with a susceptible bacteria, including those with HIV infection or extrapulmonary localizations. On the contrary, the spontaneous aggravation of multi-resistant tuberculosis, even in some cases being treated, emphasizes the need to test the strain's susceptibility to the antituberculous agents used. Certain new antibiotics, including fluoroquinolones, may play an important role in some cases. The contribution of surgery, isolation and strict compliance must also be emphasized. Resistant strains may also led to renewed indications for the Calmette-Guérin vaccine.     

Pharmacology of oral contraceptives

Oral contraceptives include two types of steroids; ethinyl-estradiol as the main estrogenic component which dose vary from 20 to 50 micrograms per tablet (mostly 30 to 35 micrograms) and progestins essentially derivatives of 19 nortestosterone. Derivatives of 19 norprogesterone such as nomegestrol acetate or ST 1435 are not used as oral contraceptives but are being evaluated through parenteral administration, e.g. implants or transdermal systems. The assessment of the pharmacological properties of these progestins indicate a high antigonadotropic and a high antiestrogenic properties for levonorgestrel and for the newer gestagens as well. Therefore very low doses are being used in the current oral contraceptives. However, there is a lower margin of security with the low dose contraceptives than with previous standard combinations and especially when concomitant medications are ingested such as enzyme-inducing agents. Selection of contraceptive methods should be discussed when specific co-medications are necessary.     

Non-drug therapeutics of idiopathic hyperuricemia

Non-drug therapeutics of idiopathic hyperuricemia especially on dietetics and kinesitherapy, and character and therapy of syndrome-X-plus are reviewed. Recently, regulation of total calorie intake is emphasized rather than prohibition of highpurinemic food. Kinesitherapy is not always recommended: Exercises beyond anaerobic threshold aggravate hyperuricemia. Syndrome-X-Plus is a newly suggested condition causes myocardial ischemia in which hyperuricemia is found to be a critical factor, and therefore, improvement of hyperuricemia may prevent the disease.     

Perspectives in antisense therapeutics

Modulation of gene expression using oligonucleotides (oligos) is currently an area of intense activity, both from therapeutic, as well as research perspectives. To develop oligos as therapeutic agents, in addition to demonstrable biological activity, in vivo metabolic stability, tissue disposition and pharmacokinetics are important considerations. Oligodeoxynucleoside phosphorothioates are the first-generation antisense analogs that have been studied extensively, and are in clinical trials against a number of disease indications. In an effort to improve the antisense properties of these compounds, mixed-backbone oligos incorporating different chemical modifications have been synthesized and evaluated for antisense activity. The present review will provide an overview of the pharmacokinetics and toxicology following intravenous, intraperitoneal, subcutaneous and oral administration of mixed-backbone oligos as second-generation antisense therapeutics.     

Pharmacology of neuropathic pain

The development of new animal models now allows the pharmacological study of the neuropathic pain. Our results concern mainly antidepressants and opiates; although the results are incomplete, they show that the different components of the pain syndrome depend on various mechanisms and require adapted treatments and that the treatment must begin as soon as possible, before plastic processes sustain a vicious circle of pain. In the future, pharmacological studies will permit better specification of indications for drugs already used, as well as the associations that improve their efficacy; studies will also encourage development of new treatments more adapted to the physiopathology of the pain syndrome.     

Pharmacology of long-term potentiation

The exotic or non-indigenous species model for deliberately introduced genetically engineered organisms (GEOs) has often been misunderstood or misrepresented. Yet proper comparisons of of ecologically competent GEOs to the patterns of adaptation of introduced species have been highly useful among scientists in attempting to determine how to apply biological theory to specific GEO risk issues, and in attempting to define the probabilities and scale of ecological risks with GEOs. In truth, the model predicts that most projects may be environmentally safe, but a significant minority may be very risky. The model includes a history of institutional follies that also should remind workers of the danger of oversimplifying biological issues, and warn against repeating the sorts of professional misjudgements that have too often been made in introducing organisms to new settings. We once expected that the non-indigenous species model would be refined by more analysis of species eruptions, ecological genetics, and the biology of select GEOs themselves, as outlined. But there has been political resistance to the effective regulation of GEOs, and a bureaucratic tendency to focus research agendas on narrow data collection. Thus there has been too little promotion by responsible agencies of studies to provide the broad conceptual base for truly science-based regulation. In its presently unrefined state, the non-indigenous species comparison would overestimate the risks of GEOs if it were (mis)applied to genetically disrupted, ecologically crippled GEOs, but in some cases of wild-type organisms with novel engineered traits, it could greatly underestimate the risks. Further analysis is urgently needed.     

The cytotoxic activities of human hemoglobin and diaspirin crosslinked hemoglobin

It is well known that hemoglobin (Hb) possesses many oxidative enzyme activities, including a pseudo-peroxidase activity. It has also been shown by many investigators that various peroxidases in the presence of hydrogen peroxide and a halide ion exert a potent cytotoxic activity toward various mammalian cell types. It has further been observed by various investigators that the administration of relatively large amounts of purified Hb or a Hb derivative to a host animal during resuscitation experiments leads to a number of unrelated types of tissue damage and cell damage in the host. The first objective of this investigation was to determine if the observed tissue and cell damage may be due to a cytotoxic activity that Hb may exert in vivo analogous to that of the peroxidases. We also showed some time ago that peroxidases are able to activate peritoneal macrophages to the cytocidal state. Hence, we also addressed the question whether or not Hb is able to activate macrophages in a similar manner. Our results were negative with regard to both questions. Further investigations indicated that, unlike the peroxidases, ferryl-Hb is unable to oxidize iodide to iodine at a measurable rate, which appears to be the reason for the lack of cytotoxic activity.     

Pharmacology of 11 beta-hydroxysteroid dehydrogenase

In a retrospective study of 73 girls and women treated in a psychiatric inpatient unit in Cape Town between 1979 and 1989, follow-up data were available for 49 (67%) of them. Internationally recommended measures were used to obtain further data, where possible, from 17 subjects (14 with anorexia, 3 with bulimia) who were 4 and more years post-hospitalisation, as well as 19 subjects (9 with anorexia, 10 bulimia) who had been out of hospital less than 4 years. Indirect information was available from 13 subjects. With regard to long-term outcome, 15 of the 17 subjects fell into the Morgan-Russell categories 'good' or 'intermediate'; in the short-term follow-up group, 14 of the 19 fell into these categories. Indirectly, we also discovered that 3 of the original subjects had died, 4 had remained ill, and 6 had recovered. These findings were similar to those from a previous study from this department and are useful feedback on the comprehensive treatment programme. They also throw light on what appears to be a culture-bound syndrome; at the time of study, the eating disorder affected mainly the middle-class white population, a pattern similar to that found elsewhere in the world.