Noninvasive remote ischemic preconditioning for global protection of skeletal muscle against infarction

The aim of this study was to investigate the efficacy and mechanism of action of a noninvasive remote ischemic preconditioning (IPC) technique for the protection of multiple distant skeletal muscles against ischemic necrosis (infarction). It was observed in the pig that three cycles of 10-min occlusion and reperfusion in a hindlimb by tourniquet application reduced the infarction of latissimus dorsi (LD), gracilis (GC), and rectus abdominis (RA) muscle flaps by 55%, 60%, and 55%, respectively, compared with their corresponding control (n = 6, P < 0.01) when they were subsequently subjected to 4 h of ischemia and 48 h of reperfusion. This infarct-protective effect of remote IPC in LD muscle flaps was abolished by an intravenous bolus injection of the nonselective opioid receptor antagonist naloxone (3 mg/kg) 10 min before remote IPC and a continuous intravenous infusion (3 mg/kg) during remote IPC and by an intravenous bolus injection of the selective delta 1-opioid receptor antagonist 7-benzylidenealtrexone maleate (3 mg/kg). However, this infarct-protective effect of remote IPC was not affected by an intravenous bolus injection of the ganglionic blocker hexamethonium chloride (20 mg/kg) or the nonspecific adenosine receptor antagonist 8-(p-sulfophenyl)theophylline (10 mg/kg) or by a local intra-arterial injection of the adenosine1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (3 mg/muscle flap) given 10 min before remote IPC. It was also observed that this remote IPC of skeletal muscle against infarction was associated with a slower rate of muscle ATP depletion during the 4 h of sustained ischemia and a reduced muscle neutrophilic myeloperoxidase activity after 1.5 h of reperfusion. These observations led us to speculate that noninvasive remote IPC by brief cycles of occlusion and reperfusion in a pig hindlimb is effective in global protection of skeletal muscle against infarction. This infarct-protective effect is most likely triggered by the activation of opioid receptors in the skeletal muscle, and remote IPC is associated with an energy-sparing effect during sustained ischemia and attenuation of neutrophil accumulation during reperfusion.     

An evaluation of the efficacy of monensin against Fasciola hepatica in the albino rat

The in vivo efficacy of monensin against Fasciola hepatica was determined in the albino rat. The results were variable, with monensin generally showing greater activity against juvenile (two-week-old) than adult (12-week-old) flukes. Significant (p less than 0.005) reductions in worm burdens were obtained only following treatment of adult flukes with 2 X 10 mg/kg monensin (52.9% efficacy), and of juvenile flukes with 1 X 10 mg/kg (42.4% efficacy) and 2 X 10 mg/kg (56.23% efficacy). Monensin administered in the diet (200 ppm) had a negligible effect on juvenile and adult fluke burdens. Prophylactic treatment of rats with monensin (100 ppm) produced a 45.5% efficacy, but this was not statistically significant. At doses of 1 X 5 mg/kg and 2 X 2.5 mg/kg, monensin had little effect on egg output by F. hepatica. No clear relationship was established between egg output and worm burden, and so faecal egg counting was not a reliable indicator of fluke burdens in the rat.     

生长抑素类似物治疗肿瘤化疗相关性腹泻的临床观察

目的评价生长抑素类似物(奥曲肽,下同)对肿瘤化疗相关性腹泻的疗效。方法对58例出现化疗相关性腹泻(CID)的患者给予奥曲肽治疗。按照NCI CTC标准,全组患者出现Ⅱ级腹泻12例,Ⅲ级腹泻38例,Ⅳ级腹泻8例。Ⅱ级、Ⅲ级CID给予皮下注射奥曲肽100μg bid或静脉持续泵入奥曲肽25μg/h,每天8 h,Ⅳ级CID给予静脉持续泵入奥曲肽25μg/h,每天12 h。结果全组58例患者的总有效率为89.7%。Ⅱ级CID奥曲肽治疗平均有效时间为2.6 d;Ⅲ级CID皮下注射奥曲肽的治疗有效时间平均为4.7 d,而静脉持续泵入奥曲肽的治疗天数平均为3.9 d,二者差异有统计学意义(P<0.05);Ⅳ级CID静脉持续泵入奥曲肽治疗平均有效时间为7.5 d。不良反应表现为5例皮下注射的患者出现一过性面部潮红,恶心,未作处理自行缓解。结论奥曲肽能有效地控制肿瘤化疗相关性腹泻,Ⅱ级以上CID患者宜采用静脉持续滴注治疗为宜。     

In vivo and in vitro studies of a putative inhibitor of cyclic guanosine 3',5'-monophosphate production.

Our main objective was to test the efficacy of 6-anilino-5,8-quinolinedione (LY83583) in vivo, a putative inhibitor of cyclic guanosine 3',5'-monophosphate (cGMP) production. If the drug proved capable of lowering plasma, vascular, and kidney levels of cGMP and of inhibiting the hypotensive effect of sodium nitroprusside and methacholine, then LY83583 could be of potential use in exploring the contribution of cGMP to cardiovascular and renal physiology. We found that when administered to trained conscious rats, LY83583 (1-mg/kg bolus, followed by a 2-hr infusion of 3 mg/kg.hr) decreased plasma cGMP concentration by 36% (P less than 0.01). Doubling the dosage of drug (2-mg/kg bolus, 6 mg/kg.hr) decreased plasma cGMP by 46% (P less than 0.05). We next measured tissue levels of cGMP ex vivo from rats that had received LY83583 or vehicle for 2 hr. The cGMP content of aortic segments when LY83583 was infused at the low dose, or renal cortical tissue when LY83583 was infused at both doses, was not significantly different from the cGMP content of tissue from rats that had received vehicle. LY83583 in doses up to 10-mg/kg bolus, followed by 6 mg/kg.hr infusion also failed to attenuate the hypotensive response to sodium nitroprusside or methacholine in conscious rats. Last, we tested whether, in our hands, LY83583 could reduce cGMP of aortic segments and kidney cortical slices in vitro. We found that after 10 min of incubation, 10(-5) M LY83583 decreased intracellular cGMP by approximately 65% and 50% in aortic and kidney tissues, respectively. In order to ascertain whether LY83583 lowered cGMP by stimulating phosphodiesterase, we incubated tissues with 10(-4) M 3-isobutyl-1-methylxanthine to inhibit the enzyme. In the presence of 3-isobutyl-1-methylxanthine LY83583 still exerted an inhibitory effect on cGMP production by aortic and kidney tissues. In conclusion, although LY83583 is a useful agent to lower renal and vascular tissues levels of cGMP in vitro, its efficacy in vivo seems doubtful.     

Influence of ruminal bypass on the pharmacokinetics and efficacy of benzimidazole anthelmintics in sheep

Oxfendazole, fenbendazole and albendazole were each administered at 5mgkg(-1) to sheep fitted with abomasal cannulae as a single bolus intra-ruminally or infused intra-abomasally at a declining exponential rate, with half-life equivalent to the rate of rumen fluid outflow. The pharmacokinetic disposition of parent compound and metabolites in plasma and abomasal fluid was determined by high performance liquid chromatography. Compared with intra-ruminal administration, intra-abomasal infusion of fenbendazole lowered the area under the concentration-time curve of drug in both plasma and abomasal fluid; intra-abomasal infusion of albendazole substantially increased maximum drug concentration and the concentration-time curve in abomasal fluid and lowered the plasma concentration time curve of the sulphoxide metabolite; intra-abomasal infusion of oxfendazole increased maximum concentration and the concentration-time curve of drug in plasma and abomasal fluid. The greater availability in abomasal fluid of oxfendazole and albendazole when given at commercial dose rates of 5 mg kg(-1) and 3.9 mg kg(-1), respectively, by intra-abomasal infusion correlated with increased efficacy of both drugs against benzimidazole-resistant Trichostrongylus colubriformis and of albendazole against benzimidazole-resistant Haemonchus contortus over that achieved by intra-ruminal administration as a single bolus.     

Occurrence of Dermatomycoses and In-Vitro Therapeutic Efficacy of Three Antifungal Drugs on the Growth of Epidermophyton Floccosum

The occurrence of dermatomycoses and the in-vitro therapeutic efficacy of some antifungal agents on dermatomycotic organisms were investigated. Of the 550 primary school children screened, the incidence was one hundred (18%), 70 were males (representing 20% of the males screened) and 30 females (15% of the females sampled). The differences between male and female prevalence were insignificant. Three species of dermatophytes were isolated and identified. These were Microsporum canis, Trichophyton tonsurans and Epidermophyton floccosum. The antifungal agents tested on E. floccosum were griseofulvin, terbinafine and ketoconazole. They produced different sized zones of inhibition against the growth of E. floccosum. Griseofulvin exhibited a 50% inhibition of growth on E. floccosum at 63.00 mg/L. Terbinafine on the other hand exhibited varying levels of inhibition of growth at varying concentrations, at 0.07 mg/L, terbinafine achieved 46% inhibition of growth on E. floccosum. The drug achieved 100% inhibition of growth on the isolate at 61.81 mg/L. In the case of ketoconazole, 50% inhibition of growth was achieved at 100 mg/L while 100% inhibition of growth was achieved at 200 mg/L. The antifungal effects of the three drugs were confirmed by broth dilution tests where terbinafine was found to be fungistatic on the growth of E. floccosum at concentrations ranging from 0.013-1.700 mg/L and was fungicidal at concentrations ranging from 0.027-1.700 mg/L. Ketoconazole was found to inhibit the growth of E. floccosum at 0.003-1.700 mg/L and was fungicidal at concentrations ranging from 0.027-1.700 mg/L. It however did not succeed in killing the isolate under the same range of concentrations. Griseofulvin exhibited fungistatic effects on the growth of E. floccusum at 0.013-1.700 mg/L. In conclusion, ketoconazole and griseofulvin were found to be fungistatic and not fungicidal while terbinafine was both fungistatic and fungicidal on the pathogen. Terbinafine was found to be the most effective drug in inhibiting E. floccosum.     

Cyclophosphamide suppresses thioredoxin reductase in bladder tissue and its adaptive response via inductions of thioredoxin reductase and glutathione peroxidase

Mammalian thioredoxin reductase (TrxR) catalyzes the reduction of oxidized thioredoxin in a NADPH-dependent manner, and contains a selenocysteine residue near the C-terminus. Glutathione peroxidase (GPx) is one of the primary antioxidant enzymes that scavenge hydrogen peroxide and organic hydroperoxides. Both TrxR and GPx play an important role in protecting against oxidative stress. Cyclophosphamide (CTX), one of the most widely prescribed antineoplastic drugs, could cause cystitis. We found that 4 h after a bolus dose of CTX (30, 90, 150, 300 and 450 mg/kg) were administrated intraperitoneally, TrxR activity was significantly decreased in a dose-dependent manner, by 32%, 44%, 68%, 87% and 99%, respectively, in comparison with control group. When fixing CTX dose at 150 mg/kg, TrxR activity changed over time, significantly reduced to 68% of the activity in comparison with control tissue at 2 h, and gradually recovered to normal level within 24 h. In addition, we found that GPx activity was induced significantly after 4h. The results of the present study suggest that marked suppression of TrxR activity could be involved in the mechanism of CTX-induced cystitis, bladder may have a protective system against tissue damage by CTX via upregulation of TrxR and GPx, which is an adaptive response to oxidative stress.     

Dose-dependent activity of albendazole against benzimidazole-resistant nematodes in sheep: relationship between pharmacokinetics and efficacy

The relationship between the pharmacokinetic behaviour and the anthelmintic efficacy of albendazole (ABZ) against benzimidazole (BZD)-resistant nematodes was studied in sheep. A micronized ABZ suspension was orally administered at two different dose levels to sheep naturally infected with BZD-resistant gastrointestinal (GI) nematodes. The experimental animals were allocated into the following groups (n = 8): (a) untreated control; (b) orally treated with ABZ at 3.8 mg/kg b.w.; and (c) orally treated with ABZ at 7.5 mg/kg b.w. Plasma samples were obtained serially over 72 h post-treatment from both treated groups and analysed by HPLC to measure the concentrations of ABZ and its sulphoxide (ABZSO) and sulphone (ABZSO(2)) metabolites. Faecal egg counts were performed prior to treatment and at the necropsy day. All experimental animals were sacrificed 10 days after treatment to perform GI worm counts. While ABZ parent drug was not recovered in the bloodstream, ABZSO and ABZSO(2) were the molecules found in plasma. ABZSO was the metabolite measured at the highest concentrations in the bloodstream for up to 36 (treatment at 3.8 mg/kg) or 60 h (treatment at 7.5 mg/kg) post-administration. There was a proportional relationship between the administered ABZ dose and the measured plasma concentrations of both ABZ metabolites. Over a 100% increment on the plasma AUC values for the anthelmintically active ABZSO metabolite was observed at the 7.5 mg/kg compared to the 3.8 mg/kg treatment. The low efficacy patterns (< 24%) observed against the GI nematodes investigated indicate a high level of resistance to ABZ given at 3.8 mg/kg an efficacious therapeutic dose rate recommended in some countries. However, the higher and prolonged plasma drug concentration measured after the 7.5 mg/kg treatment resulted in an improved efficacy pattern (estimated by both faecal egg and adult worm counts) against most of the GI nematodes studied compared to that obtained at the lower dose rate. A direct relationship between drug pharmacokinetic behaviour and anthelmintic efficacy against BZD-resistant nematodes in sheep was shown in the current work, although individual variation precluded the observation of statistically significant differences in worm counts.     

Effects of Methylprednisolone and Hyperbaric Oxygen on Oxidative Status after Experimental Spinal Cord Injury: A Comparative Study in Rats

The effects of hyperbaric oxygen (HBO) therapy or methylprednisolone on the oxidative status were evaluated in experimental spinal cord injury. Clip compression method was used to produce acute spinal cord injury rats. Hyperbaric oxygen was administered twice daily for a total of eight 90 min-sessions at 2.8 atmospheres. Methylprednisolone was first injected with a bolus of 30 mg/kg followed with an infusion rate of 5.4 mg/kg/h for 24 h. Five days after clip application animals were sacrificed and their traumatized spinal cord segment were excised. Tissue levels of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were evaluated to reflect oxidant/antioxidant status. Non-treated clip-operated animals reflected significantly higher SOD, GSH-Px and TBARS levels that were found to be significantly higher than the sham-operated. Methylprednisolone was not able to lower these levels. HBO administration diminished all measured parameters significantly; however, their levels appeared already to be high when compared with sham animals. According to these results obtained on the 5th day after induction, HBO, but not methylprednisolone, seems to procure prevention against oxidative spinal cord injury.     

Titration of subcutaneously administered eprinomectin against mature and immature nematodes in cattle.

Eprinomectin has been approved for use as a topically applied endectocide for beef and dairy cattle. To determine if eprinomectin has utility as an injectable anthelmintic, it was titrated at 0.05, 0.1, and 0.2 mg/kg s.c. against adult (Trial 1) and at 0.05, 0.1, 0.14, and 0.2 mg/kg s.c. against immature (Trial 2) stages of lung and gastrointestinal nematodes in cattle. In Trial 1, every dose of subcutaneously delivered eprinomectin showed maximal or near-maximal (> or = 99%) efficacy against Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, T colubriformis, Cooperia punctata, Nematodirus helvetianus, Oesophagostomum radiatum, and Dictyocaulus viviparus. Adult C. oncophora was the only exception. However, even against this species, the lowest dose of 0.05 mg/kg showed 93% efficacy, and the efficacious dose necessary to kill 95% (ED95) of adults was 0.056 mg/kg. In Trial 2, every dose of subcutaneously delivered eprinomectin showed maximal or near-maximal (> or = 99%) efficacy against the immature stages of all of the above species of endoparasites. As a result, ED95 values could not be calculated. Consequently, the exquisite potency against endoparasites through parenteral administration suggests that eprinomectin may also have potential utility as an injectable product for cattle.     

Comparative Investigations On the Effect of Different Dose Schedules of the Phase-Specific Drug Vincristine (Vcr) On the Proliferation Kinetics of A Solid Experimental Tumour

The aim of the present investigation was to study the effect of a high bolus injection (1 × 2.1 mg) of vincristine (VCR) during the phase of tumour growth retardation at the 14th day after transplantation and to compare the findings with the results of single (1 × 0.35 mg) and repeated (6 × 0.35 mg) applications of this cytostatic drug. Furthermore, an attempt was made to induce a synchronization of tumour cell proliferation. It was found that the effect on the volume growth was very pronounced after the high bolus injection and the repeated application of vincristine compared with the single low dose of the cytostatic drug. A synchronization of the tumour cell proliferation by flow out of the mitotic block could not be demonstrated. On the other hand a modest simultaneous recruitment of previously non-cycling tumour cells into the cell cycle occurred in the periphery of the tumour after the high bolus injection. the repeated application and the high bolus injection of VCR increased the cytostatic effect, especially in the tumour centre, related to the more slowly proliferating tumour cell compartment.     

Comparative investigations on the effect of different dose schedules of the phase-specific drug vincristine (VCR) on the proliferation kinetics of a solid experimental tumour

The aim of the present investigation was to study the effect of a high bolus injection (1 X 2.1 mg) of vincristine (VCR) during the phase of tumour growth retardation at the 14th day after transplantation and to compare the findings with the results of single (1 X 0.35 mg) and repeated (6 X 0.35 mg) applications of this cytostatic drug. Furthermore, an attempt was made to induce a synchronization of tumour cell proliferation. It was found that the effect on the volume growth was very pronounced after the high bolus injection and the repeated application of vincristine compared with the single low dose of the cytostatic drug. A synchronization of the tumour cell proliferation by flow out of the mitotic block could not be demonstrated. On the other hand a modest simultaneous recruitment of previously non-cycling tumour cells into the cell cycle occurred in the periphery of the tumour after the high bolus injection. The repeated application and the high bolus injection of VCR increased the cytostatic effect, especially in the tumour centre, related to the more slowly proliferating tumour cell compartment.     

Diatomaceous earth increases the efficacy of Beauveria bassiana against Tribolium castaneum larvae and increases conidia attachment

This research tested the suppressive ability of Beauveria bassiana (Balsamo) Vuillemin alone and in combination with diatomaceous earth against the red flour beetle, Tribolium castaneum (Herbst). Adults did not show a dose response to B. bassiana, and the addition of diatomaceous earth (DE) did not result in a significant increase in mortality. Against larvae, however, DE at 190 mg/kg grain enhanced the efficacy of B. bassiana at all concentrations ranging from 33 to 2,700 mg of conidia per kilogram of grain. The presence of DE resulted in 17- and 16-fold decreases in the median lethal concentration of B. bassiana at 56 and 75% RH, respectively. No significant differences in larval mortality in response to B. bassiana and diatomaceous earth alone or in combination were found between 56 and 75% RH. Conidial attachment to larvae was significantly greater with 190 mg/kg DE than without it. The partial analysis of lipids taken up by DE from the larvae revealed the removal of phospholipids and long-chain fatty acids. These results support the hypothesis that diatomaceous earth enhances the efficacy of B. bassiana against larval T. castaneum, at least in part by damaging the insect cuticle, thus increasing conidial attachment and making nutrients more available to conidia for their germination.     

Pattern of insulin delivery affects hepatic insulin sensitizing substance (HISS) action and insulin resistance

Hepatic insulin sensitizing substance (HISS) action accounts for 55% of the glucose disposal effect of a bolus of insulin in the fed state. To determine the effect of continuous versus pulsatile insulin delivery on HISS action in male Sprague-Dawley rats, insulin sensitivity was assessed using the rapid insulin sensitivity test (RIST) before and after a continuous, pulsatile, or bolus insulin (60 mU/kg i.v.) delivery. There was a significant difference in the RIST index after a continuous insulin infusion (247.9 mg/kg before, 73.2 mg/kg after) but not after 3 pulses where insulin action returned to baseline between pulses (211.6 mg/kg before, 191.0 mg/kg after) or single bolus (205.8 mg/kg before, 189.9 mg/kg after) insulin infusion. If a 3-pulse infusion was timed so that insulin action did not return to baseline between pulses, HISS action was suppressed. Continuous insulin infusion (10-30 min) showed progressive postinfusion blockade of HISS action. To maintain HISS-dependent insulin action, continuous insulin infusions should be avoided.     

In Vitro Antibacterial Efficacy of Cymbopogon flexuosus Essential Oil against Aeromonas hydrophila of Fish Origin and in Silico Molecular Docking of the Essential Oil Components against DNA Gyrase-B and Their Drug-Likeness

In aquaculture, diseases caused by the Aeromonads with high antibiotic resistance are among the most common and troublesome diseases. Application of herbs is emerging as a tool in controlling these diseases. Plant extracts besides disease control, favor various physiological activities in fish. In this study, essential oil of Cymbopogon flexuosus (Poaceae family) was studied in vitro for its antibacterial efficacy against two oxytetracycline (OTC) resistant and one sensitive strains of Aeromonas hydrophila. The oil was found rich (86.93 %) in oxygenated terpenoids containing 74.15 % of citral. The oil exhibited dose dependent growth inhibition of the bacteria. Mean MIC value of the oil against the sensitive strain was recorded as 2.0 mg mL⁻¹ whereas MBC value was recorded as 4.0 mg mL⁻¹. The oil was found effective against the OTC resistant isolates with the MIC and MBC values ranging from 2.67–3.33 and 4.0–6.67 mg mL⁻¹, respectively. In silico molecular docking of the essential oil components against DNA gyrase-B, a vital macromolecule in bacterial cell, was carried out to computationally asses the efficacy of the oil against the bacteria. Some of the components of the essential oil strongly bonded with the enzyme to inhibit its efficacy. Binding energy of some components of the oil was comparable to that of the conventional antibiotic, OTC. The identified phytochemicals exhibited favorable physicochemical and pharmacokinetic properties and satisfied the rule of five (Ro5).     

How effective is nicotine replacement therapy in helping people to stop smoking?

OBJECTIVE--To assess the efficacy of nicotine replacement therapy in helping people to stop smoking. DESIGN--Analysis of the results of 28 randomised trials of nicotine 2 mg chewing gum, six trials of nicotine 4 mg chewing gum, and six trials of nicotine transdermal patch. SUBJECTS AND SETTING--Subjects were self referred (responding to advertisements or attending anti-smoking clinics) in 20 trials and invited (general practice or hospital patients) in 20. Therapists in self referred trials were generally experienced in helping people stop smoking but not in invited trials. MAIN OUTCOME MEASURE--Efficacy was defined as difference in percentages of treated and control subjects who had stopped smoking at one year. RESULTS--Efficacy was highly significant (P < 0.001) for both gum and patch. Nicotine 2 mg chewing gum had an overall efficacy of 6% (95% confidence interval 4% to 8%), greater in self referred subjects than in invited subjects (11% v 3%). Efficacy depended on the extent of dependence on nicotine as assessed by a simple questionnaire; it was 16% (7% to 25%) in "high dependence" smokers, but in "low dependence" smokers there was no significant effect. The 4 mg gum was effective in about one third of "high dependence" smokers. The efficacy of the nicotine patch (9% (6% to 13%) overall) was less strongly related to nicotine dependence, perhaps because the patch cannot deliver a bolus of nicotine to satisfy craving. CONCLUSIONS--Both gum and patch are effective aids to help nicotine dependent smokers who seek help in stopping. Among the most highly nicotine dependent smokers (those craving a cigarette on waking) the 4 mg gum is the most effective form of replacement therapy; it could enable one third to stop. In less highly dependent smokers the different preparations are comparable in their efficacy but the patch offers greater convenience and minimal need for instruction in its use. Overall, nicotine replacement therapy could enable about 15% of smokers who seek help in stopping smoking to give up the habit.     

The mechanical basis of impaired esophageal emptying postfundoplication

Fundoplication (FP) efficacy is a trade-off between protection against reflux and postoperative dysphagia from the surgically altered mechanical balance within the esophagogastric segment. The purpose of the study was to contrast quantitatively the mechanical balance between normal and post-FP esophageal emptying. Physiological data were combined with mathematical models based on the laws of mechanics. Seven normal controls (NC) and seven post-FP patients underwent concurrent manometry and fluoroscopy. Temporal changes in geometry of the distal bolus cavity and hiatal canal, and cavity-driving pressure were quantified during emptying. Mathematical models were developed to couple cavity pressure to hiatal geometry and esophageal emptying and to determine cavity muscle tone. We found that the average length of the hiatal canal post-FP was twice that of NC; reduction of hiatal radius was not significant. All esophageal emptying events post-FP were incomplete (51% retention); there was no significant difference in the period of emptying between NC and post-FP, and average emptying rates were 40% lower post-FP. The model predicted three distinct phases during esophageal emptying: hiatal opening (phase I), a quasi-steady period (phase II), and final emptying (phase III). A rapid increase in muscle tone and driving pressure forced normal hiatal opening. Post-FP there was a severe impairment of cavity muscle tone causing deficient hiatal opening and flow and bolus retention. We conclude that impaired esophageal emptying post-FP follows from the inability of distal esophageal muscle to generate necessary tone rapidly. Immobilization of the intrinsic sphincter by the surgical procedure may contribute to this deficiency, impaired emptying, and possibly, dysphagia.     

Comparative efficacy of flubendazole and mebendazole on encysted larvae of Trichinella spiralis (USA strain) in the diaphragm of mice and rats

Comparative efficacy of mebendazole and flubendazole, a p-fluor analogue of mebendazole against the encysted larvae of Trichinella spiralis (USA strain) in the diaphragm of mice and rats were studied in order to provide a better understanding of the structure-activity relationship within the benzimidazole series. Drugs given 10-100 mg/kg/day for 3 consecutive days (35-37 days post-infection) or at 300 mg/kg, 35 days post infection were significantly effective in decreasing early encysted larvae in mice. No significant differences in effectiveness against the early encysted larvae could be observed between the drugs under the present experimental conditions. Mebendazole was found to be more effective that flubendazole in decreasing old encysted larvae in mice treated 70-72 days post-infection based on a comparative study of their ED50 values. When rats were given the drugs at the dose of 10 mg/kg/day for 3 consecutive days, mebendazole was significantly effective against both early and old encysted larvae while flubendazole was not.     

Relationship between reversible acetylcholinesterase inhibition and efficacy against soman lethality

Carbamate pretreatment (45% inhibition, reversible), combined with therapy, protected rats from soman-induced lethality [The Pharmacologist 23, 224 (1981)]. The present study was done to see if less than 45% inhibition protects and to see if reversible acetylcholinesterase (AChE) inhibition and efficacy against soman lethality are correlated. At 30 min pre-soman, guinea pigs and rats received (im) either pyridostigmine (Py) or physostigmine (Ph) to inhibit whole blood AChE from 10 to 70%; at 1 min post-soman (sc), they received (im) atropine (16 mg/kg)/2-PAMCl (50 mg/kg) and mecamylamine (0.8 mg/kg)/atropine (16 mg/kg), respectively. Protective ratios (PRs) were computed and they ranged from 3.1 to 7.7 for guinea pigs and from 1.8 to 2.4 for rats. In guinea pigs the PRs for Py + therapy were roughly similar to those of Ph + therapy. In both species at 30 min after im injection of Py and Ph, a linear relationship was found between percentage of whole blood AChE inhibition and ln dosage of carbamate. Positive correlation (p less than 0.05) was found between the degree of reversible AChE inhibition by pretreatment, coupled with therapy, and efficacy against soman lethality. The present data indicate that inhibition levels as low as 10% may provide some protection.     

How effective is pre-release nematode control in farm-reared red-legged partridges Alectoris rufa?

Game bird farming is associated with high parasite levels that reduce farm productivity, reduce survival after releasing, and may pose a health risk for natural populations. The efficacy of albendazole (orally, 20 mg kg(-1) was evaluated in farmed red-legged partridges naturally infected with the nematodes Aonchotheca caudinflata and Heterakis gallinarum. In treated birds body condition improved, nematode egg deposition was reduced and the proportion of gravid A. caudinflata females was reduced, but not the overall worm burdens. Albendazole was found to be 36.8% and 17.1% effective against A. caudinflata and H. gallinarum, respectively. These results indicate that the anthelmintic treatment used normally in Spanish partridge farms is not effective enough to avoid the introduction of parasites into the field after release.