A high performance liquid chromatography method for the detection of brodifacoum in serum

A procedure for the detection of brodifacoum (BDF) in serum was developed. Extraction of BDF was achieved by acidification of 2 ml of serum with 1 ml of 1.5% acetic acid followed by dual extractions with 10 ml diethyl ether and ether: acetonitrile [1:1]. In spiking experiments, 68 +/- 3, 61 +/- 4 and 65 +/- 5% of added BDF was recovered from serum containing 1000, 100 and 25 ng BDF/ml, respectively. Two high performance liquid chromatography solvent systems were used for chromatographic separation (A: 1.5% acetic acid, pH 4.5: acetonitrile [1:2] with 1% dibutylamine; and B:O.2 M tris(hydroxymethyl)aminomethane, pH 7.5:acetonitrile [1:3]). Detection limits were 75 and 3 ng BDF/ml of serum using ultraviolet absorption (254 nm) and fluorescence measurement (313 nm excitation, 375 nm emission), respectively. This method has been used successfully to monitor serum concentrations of BDF in experimental and field cases of exposure.     

The Effect of Subacute Marijuana Smoke Inhalation on Experimentally Induced Dermonecrosis by S. Aureus Infection

Dermonecrosis was induced in ICR mice by subcutaneous implantation of Staphylococcus aureus absorbed onto sterile cotton pellets. This model was used to assess the effects of marijuana smoke, marijuana placebo smoke and $DL⁹-tetrahydrocan-nabinol ($DL⁹-THC) on the local immune response to bacterial infection. Mice were exposed to 40 or 80 “puffs” of marijuana smoke, marijuana placebo smoke or air daily for 4 consecutive days. The estimated dose of $DL⁹THC per day generated from 40 or 80 puffs of marijuana smoke was 3.2 and 6.4 mg/kg, respectively. A group of sentinel (Shelf) control mice were included in each experiment. The necrotic index (NI) of mice exposed to 40 or 80 puffs of marijuana smoke were 67% and 44% of control, respectively. Air exposed mice showed a necrotic index comparable to the shelf control group. In chronically (60 days) exposed mice (80 puffs per day) the necrotic index was about 12% of control, while air-exposed mice were about 40% of control.

Placebo marijuana smoke exposed mice had a NI comparable to that of marijuana smoke exposed mice which suggested that the reduction in NI was unrelated to the pychomimetic component $DL⁹THC. To further explore which of the constituents of marijuana were responsible for the decreased NI, the ethanol extract from marijuana leaves was partioned between water (cannabinoid free) and chloroform (cannabinoid rich). Injection of the cannabinoid free fraction produced comparable decrease in the NI as observed with whole marijuana smoke, while the cannabinoid rich fraction produced no effect. $DL⁹THC at a dose of 10 mg/kg per day did not alter the NI.     

On the dual structure of the auditory brainstem response in dogs.

OBJECTIVE: To use the over-complete discrete wavelet transform (OCDWT) to further examine the dual structure of auditory brainstem response (ABR) in the dog. METHODS: ABR waveforms recorded from 20 adult dogs at supra-threshold (90 and 70dBnHL) and threshold (0-15dBSL) levels were decomposed using a six level OCDWT and reconstructed at individual scales (frequency ranges) A6 (0-391Hz), D6 (391-781Hz), and D5 (781-1563Hz). RESULTS: At supra-threshold stimulus levels, the A6 scale (0-391Hz) showed a large amplitude waveform with its prominent wave corresponding in latency with ABR waves II/III; the D6 scale (391-781Hz) showed a small amplitude waveform with its first four waves corresponding in latency to ABR waves I, II/III, V, and VI; and the D5 scale (781-1563Hz) showed a large amplitude, multiple peaked waveform with its first six waves corresponding in latency to ABR waves I, II, III, IV, V, and VI. At threshold stimulus levels (0-15dBSL), the A6 scale (0-391Hz) continued to show a relatively large amplitude waveform, but both the D6 and D5 scales (391-781 and 781-1563Hz, respectively) now showed relatively small amplitude waveforms. CONCLUSIONS: A dual structure exists within the ABR of the dog, but its relative structure changes with stimulus level. SIGNIFICANCE: The ABR in the dog differs from that in the human both in the relative contributions made by its different frequency components, and the way these components change with stimulus level.     

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann-Whitney, Kruskal-Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.     

Propylene glycol as a vehicle for percutaneous absorption of therapeutic agents.

Propylene glycol (PG) was evaluated as a vehicle for the in vivo percutaneous absorption of the hydrochloride salts of desipramine, nortriptyline, procainamide, and N-acetyl-procainamide. Each drug was administered topically to hairless (hr-1/hr-1) mice in water and in aqueous 10% and 50% PG. Mean drug concentrations in blood, brain, heart, liver, and lung were measured by high-pressure liquid chromatography after either two or three hours of topical absorption. The presence of PG generally enhanced the absorption of each drug, and the degree of enhancement appeared to be related to the percentage of PG in the dosing solution.     

Should nurses be studying bioscience? A discussion paper

The growth of bioscience knowledge over the last two decades has increased the potential benefits of scientifically based patient care by contributing to the theory of clinical care. However, there is little evidence that knowledge, derived from the human biosciences is being fully incorporated into nursing theory and practice.Nursing has developed its own unique professional body of knowledge, heavily influenced by behavioural science. If nursing theory leans towards behavioural science, but practice is devoted to problems of biological disturbance, nursing may be facing a widening theory-practice gap, greater than other professions. The theory-practice gap in nursing may be widened by the exclusion of bioscience from nursing theory. Nurses' relative disinterest in the natural sciences can be attributed both to sociological reasons and to problems stemming from the symbol-object dichotomy that recur in the teaching of natural sciences. Reflection on practice and examination of education method are suggested as strategies for re-introducing bioscience into nursing theory and practice. A challenge facing nurse educators is the integration of biological science into the nurses' conceptual ecologies. For, if nursing fails to make bioscience its own, much of the clinical welfare of patients will become a medical monopoly.     

Regulation of phospholipase C-β isozymes by G-proteins

Phospholipase C (PLC) isozymes are known to be regulated, in part, by heterotrimeric GTP-binding protein (G-protein) subunits, including Gα subunits of the G_q family and Gβγ subunits. New data show that PLC can also be regulated by a high molecular weight G-protein that doubles as a cellular transglutaminase. Furthermore, a soluble phosphatidylinositol transfer protein (PITP) has been implicated in sustaining the activity of PLC by delivering substrate to the plasma membrane. Such diverse regulatory mechanisms imply that the PLC isozymes are precisely controlled and have specific roles in generating second messengers in response to various external stimuli.