Oral ketoconazole therapy for experimental candida albicans keratitis in rabbits

Oral ketoconazole (100 mg daily for 3 weeks) markedly reduced the severity of experimental Candida albicans keratitis in a group of 10 rabbits. Clinical scores of affected eyes were statistically significantly lower in the treated group than in a control group of 10 untreated rabbits. All cultures of corneal scrapings in the treated eyes were negative on the 15th day after the inoculation, whilst three positive cultures were still obtained on the 21st day in the control animals. Histopathological examination of eyes from treated and untreated rabbits showed great differences in the intensity of inflammatory changes in the two groups.     

Efficacy of an essentifal oil of Cinnamomum zeylanicum against Psoroptes cuniculi

The aim of the present study was to investigate the in vitro and in vivo acaricidal effects of an essential oil of Cinnamomum zeylanicun leaves on Psoroptes cuniculi, a mange mite. In vitro, 2.5 ml of the essential oil diluted at different concentrations, from 10% to 0.03%, in paraffin oil were added to Petri dishes containing all motile stages of P. cuniculi. Mites mortality observed in these dishes was compared with that observed in untreated and treated (AcaCerulen R) control plates. In vivo, one group of six P. cuniculi infected rabbits was topically treated two times at seven days interval with two ml of the essential oil at the concentration of 2.5% in paraffin oil and compared with untreated and treated (AcaCerulen R) control groups of six rabbits each. After 24 h of contact, all concentrations of essential oil between 0.10 and 10% showed a good in vitro acaricidal efficacy if compared with the untreated controls (p<0.01), but only the concentrations between 0.16 and 10% turned out as active as the drug. In vivo, the treatment with the essential oil cured all infested rabbits and no statistical differences were observed with the treated control group.     

Cloricromene effect on the enzyme activities of the tryptophan-nicotinic acid pathway in diabetic/hyperlipidemic rabbits

Since alterations of tryptophan metabolism have been reported in diabetes and atherosclerosis, it was thought of interest to investigate any role of cloricromene through the influence on the oxidative metabolism of the amino acid by using diabetic/hyperlipidemic rabbits.Male 4-month-old New Zealand white rabbits, fed a diet enriched with 1% cholesterol and 10% corn oil, were made diabetic with alloxan. During the hyperlipidemic diet, a group of rabbits was treated with cloricromene (10 mg/kg/day subcutaneously plus 1.5 mg/kg/day intravenously, for 5 weeks). The other group received saline. Normometabolic New Zealand rabbits fed standard diet, treated or not with cloricromene, were used as control.The specific activities of liver tryptophan 2,3-dioxygenase and small intestine indole 2,3-dioxygenase were not significantly changed by the drug treatment. Also the specific activities of other enzymes of the kynurenine pathway in the liver and kidneys, specifically kynurenine 3-monooxygenase, kynureninase and kynurenine-oxoglutarate transaminase, did not show any significant difference in both tissues between the two groups of rabbits. On the contrary, 3-hydroxyanthranilate 3,4-dioxygenase activity in the liver of diabetic/hyperlipidemic rabbits and control rabbits treated with cloricromene showed a slight increase in comparison with untreated animals. Conversely, the specific activity of the enzyme in kidneys was not affected by the drug treatment in diabetic/hyperlipidemic animals but was reduced in controls. Aminocarboxymuconate-semialdehyde decarboxylase specific activity remained unchanged in the liver following cloricromene treatment, instead the specific activity of the enzyme in the kidneys of the diabetic/hyperlipidemic rabbits was significantly increased by the drug, with a value more than double in comparison to untreated animals. The activity of the scavenger enzyme Cu/Zn superoxide dismutase (Cu/Zn SOD) in the small intestine was also determined and found significantly increased of about twice as much in the group of diabetic/hyperlipidemic rabbits treated with cloricromene.In conclusion, in diabetic/hyperlipidemic rabbits, cloricromene appeared to influence the enzymes involved in the last steps of tryptophan oxidative metabolism through the kynurenine pathway. This, together with the antioxidant action through the activation of Cu/Zn SOD, might deserve further investigation for evaluating any link between the observed experimental findings at the level of the kynurenine pathway and the clinical effect of the drug.     

PSEUDOMONAS AERUGINOSA INFECTIONS OF THE EYE

Pseudomonas aeruginosa seldom invades the body except in persons or in organs lacking natural defenses, and usually the infection is chronic rather than acute, evoking little systemic response. When introduced into the cornea, however, as in penetration by a foreign body or in contaminated medicines, it acts with extreme virulence, in many cases causing blindness and even necessitating enucleation.Although many attempts at control of Ps. aeruginosa, even with powerful antibiotics, have been unsuccessful, polymyxin B appeared to have good effect and was tested in experimental infection of the cornea in rabbits.It was demonstrated by preliminary studies in vitro that polymyxin B was effective against nine strains of Ps. aeruginosa which on inoculation caused rapidly progressive ulcers in the corneas of rabbits.A strain of proved virulence was introduced into both eyes of each of 18 rabbits. The left eyes only were treated with subconjunctival injections at 48-hour intervals of a solution of polymyxin B, to which epinephrine was added as a vasoconstrictor to prevent rapid dispersion. The right eyes remained untreated as controls.In five of the six rabbits treated immediately after inoculation, the treated eyes remained clear, while moderate infiltration developed in the sixth. In the six rabbits not treated for 24 hours after inoculation, ulcers developed but remained localized during therapy. In those not treated for 48 hours after inoculation, ulcers developed before treatment began but did not spread as rapidly as in the controls.Hyaluronidase was added to the preparation for half the rabbits in each group but had no perceptible beneficial effect.     

Antioxidant and anticataractogenic effects of topical captopril in diquat-induced cataract in rabbits.

1-[(2s)-3-Mercapto-2-methylpropionyl]-L-proline (captopril), an antihypertensive and free radical scavenger, protected the rabbit lens from peroxidative and oxidative damage induced by 1 mM diquat in vitro. To evaluate the anticataract efficacy of captopril, an experimental group of five rabbits was treated with topical captopril (1% in 0.15 M NaCl, w/v), and 50 microliters was instilled onto both eyes four times a day for a total of 8 weeks. Following the same procedure, the eyes of five rabbits were treated with topical 0.15 M NaCl as a control for captopril treatment. At the end of the first week of treatment, a single intravitreal dose of 120 nmole diquat in 30 microliters of 0.15 M NaCl was injected into the right eye of each rabbit of both the groups. As a control for intravitreal diquat injection, the left eye of all the rabbits were injected with the diluent, 30 microliters per eye. The intravitreal diquat or its diluent injection was only for one time. From slit-lamp biomicroscopic observation of the diquat-injected right eyes, the anticataract effect of captopril in the treatment group was indicated by the finding that in four of five rabbits the cataract did not advance; whereas in four of five rabbits treated with the diluent the cataract progressed to grade 3. The lenses in the diluent-injected control left eyes of the rabbits treated with the captopril or diluent were normal. However, since the number of animals used for the in vivo studies was few, further confirmation of the anticataract effect of captopril is necessary. In diquat-injected right eyes of animals treated with captopril, the integrated rate of O2- production was about 50% less (p less than .001) in the aqueous humor, vitreous humor, and lens, compared with O2-, 33.49 +/- 2.26 microM (mean +/- SEM) in the aqueous humor, 17.12 +/- 0.75 microM in the vitreous humor, and 31.44 +/- 1.29 nmole/g wet weight in the lens of the diquat-injected right eyes treated with the diluent. Similar significant (p less than .01) differences in the production of .OH and H2O2 in eye tissues were also observed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of benzo(a)pyrene and methyl(acetoxymethyl) nitrosamine on thymidine uptake and induction of aryl hydrocarbon hydroxylase activity in human fetal oesophageal cells in culture.

Primary cultures of human fetal oesophageal cells were set up and maintained for 45 days. Epithelial cells were the dominant cell type in the culture for the first four weeks. Thereafter, both epithelial cells and fibroblasts were seen with the fibroblasts becoming the dominant cell type by the 6th week and until the cultures degenerated. The tritiated thymidine uptake showed an upward trend from day 10 up to day 30, with peak uptake at day 30 in the untreated, B(a)P treated and OAc treated cultures and decreased thereafter. The thymidine uptake levels were significantly higher in the B(a)P treated cultures when compared with levels in the untreated cultures. A concurrent increase/decrease was also seen in the cell number in all the three groups of cultures. Cultures with B(a)P and DMN-OAc showed significantly higher AHH levels as compared with untreated cultures. These results indicate that the human fetal oesophageal cells could be viably maintained under in vitro conditions for long periods of time and also showed capacity to metabolise the carcinogens through aryl hydrocarbon hydroxylase activity.     

The effect of buprenorphine on the course of disease in laboratory rabbits infected with myxoma virus

The only method of assessing the virulence of myxoma virus is to record survival times of rabbits inoculated with the virus. This raises ethical concerns about using animals in experiments where death is the end point. We investigated whether or not the opioid analgesic buprenorphine could be used in rabbits without compromising the myxoma virus virulence assay and on the presumption that animals may suffer pain during the course of the disease. Thirty, 5-month-old New Zealand White rabbits were divided into two groups stratified for weight and gender, and inoculated intradermally with 100 pfu of the Standard Laboratory Strain (SLS) of myxoma virus. At day 6 post infection (p.i.), when eyelid swelling was first seen, each animal in one group was treated with 0.03 mg/kg buprenorphine, subcutaneously, morning and evening until death. Animals in the other group were untreated. Animals were weighed daily and rectal temperatures taken morning and evening. Intake of food and water was assessed as was general demeanor including respiratory effort. There was no significant difference in mean survival time, weight change, or demeanor between the two groups. Increased respiratory effort was seen from day 10 p.i. in animals surviving up to and beyond that time but again there was no difference between groups. Animals treated with buprenorphine refused food and water a day earlier than untreated animals, and had lower temperatures immediately prior to death. It was concluded that the opiate analgesic buprenorphine can be used without compromising the current virulence assay for the SLS of myxoma virus in New Zealand White rabbits but that the clinical signs of myxomatosis that could be attributed to pain were not abrogated.     

HeNe激光对瘢痕组织影响的实验研究

目的 :寻求瘢痕组织的康复疗法。方法 :家兔 2 0只 ,在臀部一侧人工形成瘢痕。随机分为激光治疗组和对照组 ,每组 1 0只。对激光治疗组家兔于术后第 3天开始用低能量 He Ne激光照射治疗 ,每天一次 ,每次1 5分钟 ,连续照射 1 0天。于术后第 2 0天 ,将家兔全部处死 ,对每只做过实验的臀部 ,均整块地切其软组织做病理检查。结果 :激光治疗组感染消失和切口愈合平均天数分别为 4 .2天和 5.9天。对照组感染消失和切口愈合平均天数分别为 1 2 .9天和 1 4 .8天。显微镜下可见表皮增厚 ,瘢痕及横纹肌退变等异常改变。这些变化以激光治疗组为最轻 ,与对照组比 P<0 .0 1 ,有非常显著差异。结论 :早期应用 He Ne激光照射治疗 ,有防治瘢痕形成及促进瘢痕软化的作用。     

Effects of thalidomide on reproductive function and early embryonic development in male and female New Zealand white rabbits

BACKGROUND : The present work was performed to determine the effect of thalidomide exposure on reproductive function and early embryonic development. METHODS : Twenty‐five female New Zealand White rabbits were orally gavaged with 0, 10, 50, or 100 mg/kg/day thalidomide 14 days prior to mating through to gestation day 7 for a total of 22 days. Treated females were Caesarean‐sectioned approximately 29 days after the date of attempted mating. Following mating with treated females, male rabbits (25/dose) were gavaged with 0, 30, 150, or 500 mg/kg/day beginning 14 days prior to mating with a group of untreated females (25/dose). Doses were administered through mating until the day before sacrifice for a minimum of 56 days. Untreated females were Caesarean‐sectioned 29 days after the last attempted mating. Comprehensive necropsy and histopathology of the reproductive system were performed. RESULTS : Treated females had reduction in body weight gain during gestation. Mating and pregnancy parameters were unaffected by thalidomide. At 100 m/kg, litter averages for corpora lutea, implantations, litter sizes, does with viable fetuses and live fetuses decreased and the number of early resorptions, does with any resorptions, does with all conceptuses resorbed, and the percent resorbed conceptuses per litter increased. The number of early resorptions, the average number of early resorptions per litter, and the percent resorbed conceptuses per litter increased at 10 and 50 mg/kg. There were no thalidomide‐related external fetal malformations. Mating and fertility in male rabbits were unaffected by thalidomide. There was an increased incidence of flaccid testes at 150 and 500 mg/kg and of bilateral small testes in all treated groups. At 500 mg/kg, there was degeneration of the germinal epithelium of the testicles with an increase in multinucleated giant cells in seminiferous tubule and a loss of round and elongating spermatids. CONCLUSIONS : Thalidomide had no adverse effects on mating and fertility in male and female rabbits dosed up to 500 and 100 mg/kg/day, respectively, for 14 days prior to mating. After 56 day of dosing, histopathologic changes with no associated sperm abnormalities were observed in the testicles. Embryonic development NOAEL for treated females mated to untreated males was <10 mg/kg. Corresponding fertility NOAEL for treated males mated to untreated females was 500 mg/kg. Birth Defects Res B 71:1–16, 2004. © 2004 Wiley‐Liss, Inc.     

Prolonged corticosteroid treatment exerts transient inhibitory effect on prostaglandin E2 release from rabbits' eyes

In humans, the retina and choroid (the photoreceptor and its vascular layers, respectively), are affected by an immunogenic inflammatory reaction--uveitis, associated with excessive levels of prostaglandin E2 (PGE2), and treated for prolonged periods with corticosteroids, known for their inhibitory effect on prostaglandins (PGs) production. In order to assess whether this drug retains its inhibitory effect during chronic use, we investigated the effect of long-term systemic administration of corticosteroids on PGE2 release by the choroid and retina of rabbits' eyes. We used eyes traumatized by laser irradiation, in which the inflammatory reaction is associated with an enhanced PGE2 in vitro release by the choroid-retina throughout a 2-week period; levels peaked on days 1 and 7 to values 2.2- and 5.5-fold, respectively, greater than baseline. Systemic corticosteroid administration to laser-exposed rabbits curtailed the excessive PGE2 release during the first post-laser week; later the amounts released progressively increased to levels 5.5-fold higher than baseline (day 14), whereas in the corresponding untreated laser group, levels were significantly lower. PGE2 tissue content on days 7 and 14 in steroid-treated and untreated laser groups were similarly elevated. We conclude that during prolonged systemic corticosteroids treatment the steroidal inhibitory effect on enhanced PGE2 formation by the retina-choroid of laser injured eyes is transient; it is evident during the early phase following drug administration, whereas later excessive PGE2 release is resumed.     

Utilization of cholestyramine resin as a preventive treatment for antibiotic (clindamycin) induced enterotoxaemia in the rabbit.

Cholestyramine, an ion exchange resin shown to bind bacterial toxins, was utilized to treat rabbits with antibiotic induced enterotoxaemia. Three groups of 6 rabbits were administered 30 mg/kg clindamycin phosphate intravenously on day 1. One group was untreated; 2 groups were treated daily by gavage with 2 g cholestyramine in 20 ml water until day 21, starting on either day 1 or 3. Daily body weights, faecal output, faecal occult blood, food and water consumption, and body temperatures were determined. Four of 6 rabbits in the untreated group either died or were moribund and euthanased. There were no deaths in either treatment groups. Dramatic decreases in food consumption (86%), water consumption (62%), and faecal output (89%) were noted within 3 days after clindamycin administration in all groups. These parameters remained depressed throughout the study. There was no clear trend in body weight changes, body temperature, or faecal occult blood test results. Cholestyramine was effective in eliminating mortality associated with the intravenous administration of clindamycin and is recommended to prevent the development of enterotoxaemia when pyrogen testing or administering antibiotics known to induce the syndrome in rabbits.     

Modification of crescentic Masugi nephritis in the rabbit by Bredinin, a new immunosuppressant

Experiments were undertaken to ascertain whether progression of crescentic Masugi nephritis in rabbits could be prevented by the administration of Bredinin (BR). Crescentic glomerulonephritis can be induced with high reproducibility by intramuscular preimmunization on day 1, followed by intravenous injections on days 3 and 5 of nephrotoxic duck gamma-globulin (NTD gamma-gl). 30 rabbits were divided into 3 groups including controls (group 1). Two groups of 10 nephritic rabbits were each treated with 10 mg/kg of BR either after or before the development of proteinuria (groups 2 and 3). In group 3, the onset of proteinuria showed a significant delay and duration of survival was significantly prolonged, compared with controls. Serum antibody titers after day 8 and creatinine levels after day 10, as well as the initial amounts of proteinuria, were also significantly lower during treatment in group 3 than in controls. Histologically, the prominent diffuse intra- and extra-capillary proliferation with monocyte accumulations observed in the control group were markedly diminished in group 3. These results suggest that early treatment in crescentic glomerulonephritis with BR will suppress the production of humoral antibody and prevent progression of the glomerular lesions.     

Efficacy of an essential oil of Eugenia caryophyllata against Psoroptes cuniculi

The acaricidal activity of Eugenia caryophyllata essential oil was evaluated in vitro and in vivo on Psoroptes cuniculi, a mange mite. In vitro, different concentrations of the oil were tested and the observed mites mortality was compared with that observed in untreated and treated (Acacerulen R^®) controls. In vivo, six P. cuniculi infected rabbits were topically treated with the oil diluted at 2.5% and compared with untreated and treated control groups of six rabbits each. In vitro, up to the concentration of 0.10% the oil gave highly significant (P < 0.01) percentages of mite mortality respect to the untreated controls, but only up to 0.16% it showed the same efficacy of Acacerulen R^®. In vivo, the treatment with the essential oil cured all infested rabbits and no statistical differences were observed respect to the treated control group. The untreated rabbits remained infested.     

Retinoic acid enhances the displacement of newly synthesized hyaluronate from cell layer to culture medium during early phases of chondrogenesis

Chondrogenic differentiation in mouse limb bud mesenchymal cells cultured at high density was suppressed by supplementation of the medium with retinoic acid (1 microgram/ml or 3.3 X 10(-6) M). Since in control medium overt chondrogenesis begins on day 3, retinoic acid was introduced on day 2 so that the relationship between initial biosynthetic changes and inhibition of chondrogenesis could be studied. During the first 24 h of exposure the treated cells remained viable but suffered 10% inhibition in growth and synthesized [3H]glucosamine-labeled glycosaminoglycan at a level 24% below untreated cells. The amount of labeled hyaluronic acid released into the culture medium by the treated cells was, however, 2-fold greater, on a per cell basis, than that in the untreated cultures. It is suggested that the displacement of hyaluronate may play a role in the disruption of mesenchymal cell differentiation and of limb morphogenesis as observed in other systems.     

Immunological evidence of chemotherapeutic action of mebendazole against Ancylostoma ceylanicum (Looss, 1911) in hamsters (Mesocricetus auratus)

The immunological responses in hamsters during treatment with mebendazole against Ancylostoma ceylanicum are studied. Indirect haemagglutination (IHA) counterimmunoelectrophoresis (CIEP), passive cutaneous anaphylaxis (PCA), foot pad swelling for immediate (ITH) and delayed (DTH) types of hypersensitivities were employed for measuring the responses. Serum antibody which was 1:32 before treatment increased to the maximum of 1:512 (control 1:128) on the 10th day and it declined subsequently. The CIEP test was positive for 10 days and then became negative. The PCA test was positive throughout the observation period both in the treated and untreated groups. Foot pad swelling for ITH and DTH responses were comparatively more prominent than in the untreated control up to the 20th day and then both decreased simultaneously. The immunological responses remained prominent for a longer period and decreased more slowly in the untreated control group.     

Functional Effects of Short-Term Treatment with Amiodarone on Thyroid Tissues of the Rabbit

The effect of short-term treatment with Amiodarone on thyroid gland tissue was studied in a group of 26 New Zealand albino rabbits. Ten rabbits were left untreated and served as controls; the remaining animals were treated with 10 mg/kg/day Amiodarone. The serum levels of serum triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels were measured at days 0 (baseline), 7, 30, and 45. The serum selenium levels were also measured, but only on days 0 and 45 of the experiment. At the end of the experiment the animals were sacrificed and the levels of selenium, T3, T4, and iodine were determined in thyroid tissue. After 30 days treatment the values of T3 were significantly lower than those of the untreated controls or the baseline levels (p < 0.001). The T4 level was significantly lower and the TSH value was significantly higher after 45 days of Amiodarone (p < 0.001). In thyroid tissue the T3, T4, and iodine levels were significantly higher in the treated group when compared to untreated controls (p < 0.05). These results show that Amiodarone induces changes in the hormone levels in both serum and thyroid tissues, as well as in the amount of iodine taken up by the thyroid gland in rabbits.     

Use of a Taqman PCR to determine the response of Mycoplasma haemofelis infection to antibiotic treatment

A quantitative Taqman polymerase chain reaction (PCR) assay was used to evaluate the response of Mycoplasma haemofelis experimentally infected cats to three antibiotic treatment regimes. Sixteen cats were intravenously inoculated with M. haemofelis from a chronically infected donor. The cats were randomly assigned to one of four treatment groups each containing four cats: oral doxycycline at 10 mg/kg/day for 14 days, oral enrofloxacin at 5 mg/kg/day for 14 days, oral enrofloxacin at 10 mg/kg/day for 14 days, and an untreated control group. DNA, extracted from blood samples collected on days 0, 7, 14, 21, 25, 28, 32, 35, 42 and 54 post-inoculation (PI), was subjected to quantitative Taqman PCR. The M. haemofelis copy number was significantly lower in the doxycycline group (P=0.008), the 5 mg/kg/day enrofloxacin group (P=0.006) and the 10 mg/kg/day enrofloxacin group (P=0.005) compared to the untreated control group. No significant differences were found between any of the three antibiotic treated treatment groups. All three antibiotic treatment regimes evaluated in this study were effective at reducing M. haemofelis copy number.     

Stimulation by granulocyte-macrophage colony-stimulating factor of Leishmania tropica killing by macrophages.

The intracellular protozoan parasite Leishmania tropica was found to survive unharmed and to multiply for several days in normal mouse peritoneal macrophages. In contrast, when infected monolayers were treated with GM-CSF, there was a continuous decrease in the percentage of infected cells, reaching less than 10% on day 4 in culture, compared to about 30% in normal controls. Microscopic observations showed an increased number of dead parasites in GM-CSF treated infected cells. Within 5 hr of incubation with GM-CSF, almost 40% of intracellular parasites showed morphologic damage, compared to less than 10% in untreated cells. Pretreatment of macrophage monolayers with pure GM-CSF before infection led to an increased level of phagocytosis of L. tropica parasites as reflected by the percentage of infected cells and the increased number of parasites in each infected cell. GM-CSF treated cultures showed 73% infected cells containing a mean of five parasites per cell, as compared to controls in which only about 50% of macrophages were infected with only two parasites per cell. The number of dead parasites per cell was 5-fold higher in the GM-CSF treated cultures at 2 hr. After 24 hr the percentage of infected GM-CSF treated cells was less than one-third that in the control cultures.     

Proliferative diabetic retinopathy: treatment with xenon-arc photocoagulation. Interim report of multicentre randomised controlled trial.

One hundred patients with symmetrical proliferative diabetic retinopathy had one eye randomly chosen for treatment with xenonarc photocoagulation while the other was left untreated as a control. Patients were subdivided into those with new vessels on both optic discs and those with only peripheral new vessels. In patients with new vessels on the optic discs the vision of the untreated eyes deteriorated more than that of the treated eyes and the difference in deterioration was significant after one, two, and three years. There was no such difference in patients who had only peripheral new vessels. Eighteen patients had become blind in one or both eyes by the last assessment, but only one patient became blind in the treated eye without concomitant blindness in the untreated eye. Thirteen were blind only in the untreated eye. Both photographic and ophthalmoscopic examinations showed that new vessels on the disc regressed more in the treated eyes than in the untreated ones. As some forms of diabetic retinopathy are now treatable, early diagnosis and evaluation is increasingly important.