New thinking for filth fly control: residual, non-chemical wall spray from volcanic glass.

Filth flies are of medical and veterinary importance because of the transfer of disease organisms to animals and humans. The traditional control methods include the use of chemical insecticides. A novel mechanical insecticide made from volcanic glass and originally developed to control mosquitoes (Imergard™ WP; ImG) was investigated for control of adult grey flesh flies, Sarcophaga bullata (Parker), secondary screwworms, Cochliomyia macellaria (F.), and house flies, Musca domestica L. In a modified WHO cone test device, the time to 50% mortality (LT50 ) when applied at 5 g/m2 (tested at 30 °C and 50% relative humidity (rH)) was 7.1, 4.3 and 3.2 h, respectively. When knockdown was included, the LT50 s were 5.5, 1.5 and 2.8 h, respectively. Application rates of 1.25 and greater g/m2 had the shortest LT50 s. The time to the LT50 increased for M. domestica as rH increased, but ImG was still active at the highest rH tested of 70%. Scanning electron micrographs showed ImG was present on all body parts, unlike that for mosquitoes where it was found mostly on the lower legs. These first studies on the use of Imergard WP against flies suggest this could be an alternative method for filth fly control.

Intravenous lipid emulsion-augmented plasma exchange in a rabbit model of clomipramine toxicity; survival, but no sink.

INTRODUCTION: Intravenous lipid emulsion (ILE) has been shown to ameliorate toxicity from lipophilic xenobiotics, attributed in part through sequestration to circulating lipid droplets (sink). We postulated additional benefit with plasma exchange therapy undertaken subsequent to lipid injection, hypothesising enhanced blood carriage of lipophilic toxin to increase yield when combined with an extracorporeal method of elimination. METHODS: Instrumented rabbits underwent clomipramine infusion at 3.2 mg/kg/min to target mean arterial pressure (MAP) of 50% baseline, then continuously at 2 mg/kg/min to death or 90 min. Resuscitation with saline (Control), sodium bicarbonate (BIC), ILE, or lipid emulsion plus cycled plasma exchange (LEPE), was commenced on attaining target MAP. RESULTS: Greater survival was observed in animals receiving lipid emulsion from both LE and LEPE groups (Control median 12.0 [IQR 10.5 ­ 20] min, BIC median 30 [IQR 19 ­ 33] min, LE 85 [IQR 30 ­ 90] min, LEPE 90 min; P 0.0001). No difference was observed in MAP, Heart Rate, or Electrocardiograph QRS duration between surviving LE and LEPE animals at 90 min. Mean plasma exchange of 52%circulating plasma volume returned only 0.04% of the administered clomipramine load in LEPE group animals. CONCLUSIONS: Infusion of lipid emulsion resulted in greater survival in this rabbit model of intravenous clomipramine toxicity. Plasma exchange performed in conjunction with administration of lipid emulsion failed to result in significant extracorporeal clomipramine elimination. Intravascular lipid sequestration of clomipramine appears an inadequate sole explanation for the beneficial effects of lipid emulsion.

Hypertonic sodium bicarbonate versus intravenous lipid emulsion in a rabbit model of intravenous flecainide toxicity: no difference, no sink.

CONTEXT: The use of intravenous lipid emulsion (ILE) as an antidote in non-local, anaesthetic drug toxicity has generated considerable interest. Flecainide is a lipophilic anti-arrhythmic with a significant cardiotoxic profile, with blockade of sodium and potassium channels causing arrhythmias and shock in severe toxicity. ILE has been proposed as a treatment option in severe flecainide toxicity refractory to other modalities. OBJECTIVE: We compared the effects of ILE and hypertonic sodium bicarbonate in a rabbit model of flecainide toxicity. MATERIALS AND METHODS: Twenty sedated and ventilated New Zealand White Rabbits received flecainide infusion titrated to a mean arterial pressure (MAP) of 60% baseline, which was defined as toxicity. The rabbits then received either sodium bicarbonate or ILE, and the flecainide infusion was reduced in an attempt to model ongoing enteric absorption. MAP and heart rate were recorded every minute for 15 min and plasma flecainide concentration was measured at toxicity and 15 min. ECG QRS duration was recorded at baseline, toxicity and at 5, 10 and 15 min post-toxicity. RESULTS: No difference was observed in heart rate (p = 0.2804), MAP (p = 0.1802) or QRS duration (p = 0.7471) between groups. The immediate rate of rise in MAP was greatest in the bicarbonate group in the 5 min immediately post-toxicity. CONCLUSIONS: In this study, no differences were observed between an active control of hypertonic sodium bicarbonate and ILE for the primary endpoint of MAP at 15 min nor for QRS duration at any timepoint. There was a transient rapid increase in blood pressure seen in the sodium bicarbonate group that was not sustained. No increase was seen in blood concentration of flecainide in the ILE group, suggesting no 'lipid sink' for flecainide in this model. More research is warranted to define any role for ILE in flecainide toxicity.

The effect of lipid emulsion on depth of anaesthesia following thiopental administration to rabbits.

Intravenous lipid emulsion has proven benefit in lipophilic drug-induced cardiotoxicity. Its effect in reversal of central nervous system depression secondary to overdose with lipophilic psychotropic agents remains uncertain. Twenty adult New Zealand White rabbits were anaesthetised with 20 mg.kg(-1) thiopental and randomised to receive either 4 ml.kg(-1) saline 0.9% or 4 ml.kg(-1) lipid emulsion 20% immediately afterwards. Depth of anaesthesia was monitored using bispectral index (BIS) at 1-min intervals. Duration of anaesthesia was measured as time to regain the righting reflex (ability of the animal to right spontaneously from dorsal recumbency to sternal recumbency). The BIS was greater in the control group (p = 0.011). The greatest BIS differential was observed immediately following treatment (mean (SD) BIS 75.0 (9.5) for saline vs 58.6 (10.4) for lipid, 95% CI 5.75-27.1; p < 0.001). No difference was observed in duration of anaesthesia (mean (SD) 15.5 (0.8) min for saline vs 15.6 (0.7) min for lipid, p = 0.86). Lipid emulsion administration may serve to increase central nervous system depression in the early phase of lipophilic toxin distribution.

Effect of hypertonic saline on electrocardiography QRS duration in rabbit model of bupivacaine toxicity resuscitated by intravenous lipid.

Intravenous lipid emulsion is established therapy for bupivacaine induced cardiotoxicity. The benefit of combined hypertonic saline and lipid treatment is unexplored. In this experiment, sedated rabbits were resuscitated from bupivacaine-induced asystole with intravenous lipid according to the Association of Anaesthetists of Great Britain and Ireland's guideline, or by identical lipid dosing with hypertonic saline: 6 mEq x kg(-1) 21% sodium chloride. Early electrocardiography QRS prolongation was less with lipid plus hypertonic saline (mean (SD) QRS 0.19 (0.07) s lipid only vs 0.09 (0.01) s lipid plus hypertonic saline; p = 0.003) at 9 min though not different from the lipid only group at 20 min. No difference was observed in rates of circulatory return (7/10 lipid only and 9/10 lipid plus hypertonic saline; p = 0.58) or survival (5/10 lipid only and 6/10 lipid plus hypertonic saline; p = 1.00). Some benefit to cardiac conduction may be afforded by hypertonic saline co-administered with lipid emulsion in bupivacaine-induced cardiotoxicity.

Evaluation of the Association of Anaesthetists of Great Britain and Ireland lipid infusion protocol in bupivacaine induced cardiac arrest in rabbits.

Infusion of lipid emulsion has been demonstrated to facilitate return of spontaneous circulation in animal models and human cases of local anaesthetic induced cardiac arrest. Guidelines for lipid application exist; however, experimental evidence of efficacy at recommended dosing is lacking. In 20 sedated, mechanically ventilated, and invasively monitored New Zealand White rabbits, asystole was induced via bolus bupivacaine injection. Animals were randomised to receive either 20% Intralipid administered according to Association of Anaesthetists of Great Britain and Ireland guidelines, or identical volumes of 0.9% saline solution, in addition to standard Advanced Cardiac Life Support resuscitative measures. Seven lipid treated rabbits developed return of spontaneous circulation vs four saline treated animals (p = 0.370). A trend toward sooner return of spontaneous circulation in the lipid treated group was observed (2.4 (0.53) vs 3.8 (1.7) min; p = 0.082). Five animals in the lipid treated group survived to protocol termination vs nil animals from the saline treated group (p = 0.033). The current Association of Anaesthetists of Great Britain and Ireland lipid infusion protocol provides a useful beginning for lipid emulsion administration.

Recent advances in solventless organic reactions: towards benign synthesis with remarkable versatility.

A paradigm shift away from using solvents in organic synthesis as solventless reactions can lead to improved outcomes, and more benign synthetic procedures, in for example aldol condensation reactions, sequential aldol and Michael addition reactions en route to Kröhnke type pyridines, reactions leading to 3-carboxycoumarins, benzylidenes, 4-aryl-1,4-dihydropyridines and 2-aryl-1,2,3,4-tetrahydroquinazolines, and oligomerisation reactions for the synthesis of cavitands; kinetic considerations for the reaction of two solids can only be explained if a eutectic melt is formed during the reaction.

Chest conduction properties and ECG equalization.

In common practice of detecting and recording biomedical signals, it is often implicitly assumed that the propagation, through the whole circuit human body-electrodes recording devices, is frequency and voltage independent. As a consequence, clinicians are not aware that recorded signals do not correspond faithfully to the original electrical activity of organs under investigation. We have studied the transmission of electrical signals in human body at various voltages and frequencies to understand if and to which extent the most diffused stimulating and recording techniques used in medicine are affected by global body conduction properties. Our results show that, in order to obtain a more faithful detection of electrical activity produced or evoked by human organs (e.g. EGG, electromyography, etc.), it is convenient to 'equalize'' recorded signals. To this purpose, two equalization techniques are proposed, based, respectively, on a simple hardware filtering during acquisition, or FFT post-processing of the acquired signals. As an application, we have studied the transmission of electrical signal in human chest and have compared equalized high frequency ECG signals with raw (original) recordings.

Effects of tail alkyl chain length (n), head group structure and junction (Z) on amphiphilic properties of 1-Z-R-D,L-xylitol compounds (R = CnH2n+1).

In the family of 1-Z-R-D,L-xylitol, we have determined the main amphiphilic properties of esters (Z = OCO) as a function of alkyl chain length (R = CnH2n+1, n = 4-17). A classical decrease of critical micelle concentration with the increase in the alkyl chain has been found. With water, esters displayed lamellar phases at temperatures of 25 degrees C or higher. The extent of hydrophilic/lipophilic balance range obtained by emulsification method can be proven to be of interest for pharmaceutical applications. The results were compared with those obtained in previous investigations, i.e. for alkyl-substituted xylitol, with thioether (Z=S) and ether (Z=O) linking groups in order to discuss the role of the junction nature. Likewise, they were compiled with the results related to their D-glucose homologues, in order to put forward the effects of the head group configuration, cyclic or acyclic.

The effect of chemotaxis and chemokinesis on leukocyte locomotion: a new interpretation of experimental results.

A mathematical model is developed to describe the motion of leukocytes through a Boyden chamber. The model is based on the Keller-Segel model of cell motion and comprises three partial differential equations which describe the evolution of the neutrophils, the chemoattractant, and a neutrophil-derived chemokinetic factor. Where other authors have concentrated on chemotaxis, here attention is focused on the manner in which the chemokinetic factor influences neutrophil locomotion. Numerical simulations show how the number of neutrophils initially placed on top of the chamber affects cellular motion through the system and reproduce the qualitative behaviour observed by Takeuchi & Persellin (Am. J. Physiol. 236, C22-C29). In particular, the simulations show how dense packing of the neutrophils increases the levels of the chemokinetic factor. This enhances random cell motion and increases the speed with which the neutrophils reach the source of chemoattractant. For a particular asymptotic limit of the system parameters, the model reduces to a nonlinear partial differential equation for the neutrophils. Similarity solutions of this caricature model yield algebraic expressions relating the speed with which the neutrophil front penetrates into the chamber to the number of neutrophils initially placed on top of it. The implications of the results are also discussed.

Mycobacterium fortuitum endocarditis in a patient with chronic renal failure on hemodialysis.

A case of infective endocarditis due to M. fortuitum in a 54 yr old female with chronic renal failure on hemodialysis is presented. Clinical, microbiological and autopsy findings are discussed.

Cyclophosphamide loaded albumin microspheres II. Release characteristics.

The purpose of this investigation was to evaluate the release characteristics of cyclophosphamide (CP) from glutaraldehyde stabilized human serum albumin microspheres, and to study the effect of the extent of cross-linking, the amount of the stabilizing agent and the size of the microspheres on the in vitro release of CP. Microspheres were prepared by emulsion polymerization method using two different volumes (0.1 and 0.7 ml) of glutaraldehyde solution (25 per cent) and two different crosslinking durations (15 min and 1 h). The resulting mean particle size of the microspheres also varied between 2.5 microns and 3.7 microns. The total CP content in microspheres was analysed from the surface drug and the entrapped drug.

Freeze-drying of emulsions--influence of congealing on granulometry research of a cryoprotective agent.

Emulsions of three different size distributions and five oil/water ratios of the finest of these distributions were congealed according to three different congealing processes before the freeze-drying operation. The influence of the various cryoprotective agents added was studied and the size change of the dispersed phase after congealing was examined.

Heart rate and blood pressure changes during sleep-waking cycles and cataplexy in narcoleptic dogs.

Cataplexy is the abrupt loss of muscle tone experienced by narcoleptics. It is usually precipitated by strong emotions or athletic activity. It has been hypothesized that cardiovascular variables have a role in the triggering of cataplexy. In the present study, we have utilized the narcoleptic canine model to directly investigate changes in heart rate and blood pressure in relation to cataplectic episodes. We found that heart rate increased 18% on average in the 20 s preceding cataplexy onset and then fell during cataplexy. Thus, from a cardiovascular standpoint, cataplexy can be subdivided into two very different periods, the cataplexy onset period with very high and declining heart rate, and the period greater than or equal to 10 s after onset, with greatly reduced heart rate. Heart rate at cataplexy onset was significantly higher than heart rate in rapid-eye-movement (REM) sleep, non-REM sleep, and quiet waking. Blood pressure did not markedly change before the onset of spontaneous cataplexies but decreased significantly during cataplexy. Although blood pressure increases did not precede spontaneous cataplexies, sudden increases in blood pressure, induced pharmacologically or by obstruction of the descending aorta, triggered cataplexy in the most severely affected subjects. A hypothesized role for cataplexy as a homeostatic reflex, triggered by interactions between blood flow, central chemoreceptors, and atonia control mechanisms in the medial medulla, is discussed.

Approach to the direct intramolecular localization of antigenic determinants in Androctonus australis hemocyanin with monoclonal antibodies by molecular immunoelectron microscopy.

Monoclonal antibodies (mAb) directed vs. subunits from hemocyanin (Hc) of the scorpion Androctonus australis were used in molecular immunoelectron microscopy (MIEM) to directly localize the epitopes within the subunits. Four types of mAb were used. First, mAb 6302, an IgG clone highly specific for subunit Aa 2, produced with native hemocyanin long strings composed of hemocyanin molecules in the side view and in the 45 degrees view. At lower concentration, "parachute" and "butterfly" structures composed of two Hc molecules and one monoclonal immunoglobin G (IgG) molecule were obtained. Fab fragments prepared from mAb 6302 bound exactly on the top and bottom edges of the molecule. The second type of mAb (6003), directed vs. subunit Aa 2, produced nice immunocomplexes with the free subunit but nothing with the native oligomer. It is suggested that due to steric hindrance or to conformational changes the epitope is not accessible in the native molecule. The third mAb belonged to the IgM class and apparently bound Hc in the Aa 2 area. However, because of the difficulty of separating the immunocomplexes from the residual mAb and the polymorphism of the IgM molecules, monoclonal IgM are no longer used for MIEM. The last type of mAb (5701) had a high affinity and a high specificity for subunit Aa 6. It produced two types of immunocomplexes with native Hc. The two types differed by a 180 degrees rotation around one of the Fab arms. These complexes, which support recent results of Wrigley et al. [Wrigley, N. G., Brown, E. B., & Skehel, J. J. (1983) J. Mol. Biol. 169, 771-774] and of Roux [Roux, K. H. (1983) Eur. J. Immunol. 14, 459-464], indicate that monoclonal IgG have a high degree of rotational flexibility around the Fab arm. Monoclonal antibody 5701 bound exactly at the corner of the molecule in the area where subunit Aa 6 is known to be located. The MIEM approach of the location of the epitope requires the model of the architecture and of the quaternary structure to be very precise. Thus, recent findings of Gaykema et al. [Gaykema, W. P. J., Hol, J. M., Vereijken, J. M., Soeter, N. M., Bak, H. J., & Beintema, J. J. (1984) Nature (London) 309, 23-29] and of Van Heel et al. [Van Heel, M., Keegstra, W., Schutter, W., & Van Bruggen, E. F. J. (1983) Life Chem. Rep., Suppl. Ser. 1, 69-73] led to a reexamination of previous models.(ABSTRACT TRUNCATED AT 400 WORDS)