Pathogenesis of Babesia caballi infection in experimental horses

OBJECTIVE: The spread of nosocomial multiresistant microorganisms is affected by compliance with infection control measures and antibiotic use. We hypothesized that "colonization pressure" (ie, the proportion of other patients colonized) also is an important variable. We studied the effect of colonization pressure, compliance with infection control measures, antibiotic use, and other previously identified risk factors on acquisition of colonization with vancomycin-resistant enterococci (VRE). METHODS: Rectal colonization was studied daily for 19 weeks in 181 consecutive patients who were admitted to a single medical intensive care unit. A statistical model was created using a Cox proportional hazards regression model including length of stay in the medical intensive care unit until acquisition of VRE, colonization pressure, personnel compliance with infection control measures (hand washing and glove use), APACHE (Acute Physiology and Chronic Health Evaluation) 11 scores, and the proportion of days that a patient received vancomycin or third-generation cephalosporins, sucralfate, and enteral feeding. RESULTS: With survival until colonization with VRE as the end point, colonization pressure was the most important variable affecting acquisition of VRE (hazard ratio [HR], 1.032; 95% confidence interval [C1], 1.012-1.052; P=.002). In addition, enteral feeding was associated with acquisition of VRE (HR, 1.009; 95% CI, 1.000-1.017; P=.05), and there was a trend toward association of third-generation cephalosporin use with acquisition (HR, 1.007; 95% CI, 0.999-1.015; P=.11). The effects of enteral feeding and third-generation cephalosporin use were more important when colonization pressure was less than 50%. Once colonization pressure was 50% or higher, these other variables hardly affected acquisition of VRE. CONCLUSIONS: Acquisition of VRE was affected by colonization pressure, the use of antibiotics, and the use of enteral feeding. However, once colonization pressure was high, it became the major variable affecting acquisition of VRE.     

Babesia canis infection in canine-red blood cell-substituted SCID mice

We have developed a mouse model for Babesia canis infection using severe combined immunodeficiency (SCID) mice whose circulating red blood cells had been substituted with canine red blood cells. Substitution of red blood cells in SCID mice was achieved by repetitive transfusions of canine red blood cells, together with administration of an antimouse red blood cell monoclonal antibody. Following inoculation of canine-red blood cell-SCID mice with B. canis, parasites proliferated in the canine red blood cells that had been transfused into the SCID mice, resulting in much higher parasitaemia than that observed in dogs. In an attempt to demonstrate the utility of this mouse model, three antiprotozoal drugs, diminazene diaceturate, clindamycin and oxytetracycline, were examined for their efficacy to inhibit the growth of B. canis in canine-red blood cell-SCID mice. The mouse model clearly showed that diminazene diaceturate and oxytetracycline were capable of eliminating B. canis from the canine-red blood cell-SCID mice, whereas clindamycin exhibited only a static effect as parasitaemia relapsed upon cessation of drug administration.     

Escape conditioning in wild and domestic Norway rats.

Tested 16 female wild (lab-reared) and 16 female domestic Norway rats for acquisition of a conditioned escape response. To escape from an aversive stimulus (air blasts) Ss were required to open 1 of 8 doors (simulated burrow entrances) on the presence of a visual cue. Stocks did not differ in the rate of conditioning. Wild Ss exhibited significantly shorter latencies for ambulation and escape than domestic Ss. Removal and reinstatement of the visual cue following acquisition confirmed that the Ss used the cue for orientation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A natural food aversion in Norway rats.

During a single 1-hr feeding test, adult male Norway rats were offered intact carcasses of adult male rodents, sacrificed by CO? asphyxiation. In Exp I, 79 Ss fed more readily on conspecifics dead 24–220 hrs than on conspecifics dead 10 min or 6 hrs. In Exp II, 22 Ss fed readily on roof rats (Rattus rattus) whether they had been dead 10 min or 24 hrs. In Exp III, 15 Ss rendered anosmic by zinc sulfate treatment fed more readily on conspecifics dead for 10 min than did 17 controls. In Exp IV, 34 Ss consumed more flesh from house mice coated with roof rat urine than from mice coated with Norway rat urine. It is concluded that Norway rats exhibit a natural aversion to feed on the intact carcasses of freshly sacrificed adult conspecifics in the sense that they are more likely to feed on other species of rodent. The aversion diminishes with the dissipation of the chemoreceptive cue(s) identifying the carcass as a conspecific. (64 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The brown Norway rats and the kinin system

In 1979, we found a strain of kininogen-deficient Brown Norway rats. Since then, several studies have used these animals as negative controls of the involvement of the kinin system in physiological and pathophysiological processes. The cause of this deficiency has now been elucidated. This article reviews studies performed with these kininogen-deficient rats. These investigations have mainly focused on the links between the kinin system and the kidneys, hypertension, salivary glands, acute inflammatory reactions, cysteine proteinase inhibition, lymphatic tissues, coagulation, and cardiovascular shock states.     

Ontogeny of defensive reactions in Norway rats.

In 3 experiments, 219 Sprague-Dawley albino rats of several ages were presented with stimuli (a caged domestic cat, a footshock, and a suddenly moving object) known to be aversive to adults and disruptive of behavior in mature animals. 20-day-old Ss were relatively unaffected by these events, while Ss aged 30 days and older tended to reduce their locomotion and freeze upon the presentation of these cues. Data are consistent with R. C. Bolles's (1970, 1971) hypothesis that shock-elicited responses are innate defensive reactions. It is suggested that the inefficient passive avoidance learning in juvenile rats may result from their deficit in shock-induced freezing. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Domestication, sophistication, and avoidance in Norway rats.

Administered successive 1-way and 2-way avoidance tasks which included treatments of postweaning handling to docility, prior learning sophistication, and differential shock intensity. In this 2-stage paradigm, with 32 wild and 32 hooded Long-Evans rats, escape and avoidance behaviors of wild and laboratory Ss were indistinguishable. Sophistication in laboratory-learning experience and high shock contributed significantly to the performance of both wild and domestic Ss in 1-way, but not 2-way, avoidance. In contrast, effects of handling were apparently negligible. Findings do not support the notion of degeneracy of learning ability in the domesticated rat. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Specific immune responses are required to control parasitemia in Babesia equi infection

Horses possessing a normal immune system and spleen often control infection caused by Babesia equi. However, splenectomized horses are unable to control B. equi infection and usually succumb to the infection. To investigate the role of the spleen in the control of B. equi infection in the absence of specific immune responses, two 1-month-old foals with severe combined immunodeficiency (SCID) and two age-matched normal foals were inoculated with B. equi. The SCID foals became febrile seven days postinoculation and developed terminal parasitemias of 41 and 29%. The SCID foals had greater than 50% decreases in indices of total erythrocytes, packed-cell volumes, and hemoglobin concentrations. Both SCID foals were euthanized in extremis at 10 days postinoculation. As expected, the serum of the SCID foals lacked detectable antibodies to B. equi antigens. In contrast, the normal foals inoculated with B. equi produced detectable anti-erythrocyte-stage parasite antibodies by 7 days and controlled clinical disease by 12 days postinoculation. Although SCID foals lack functional T and B lymphocytes, they do possess complement, macrophages, granulocytes, and natural killer cells, as well as a spleen. Therefore, the data indicate that specific immune responses are required to control B. equi parasitemia but are not required for erythrocyte lysis in infected horses. Furthermore, the spleen is not able to control B. equi parasitemia in the absence of specific immune responses to parasite antigens.     

Free-operant comparisons of wild and domestic Norway rats.

Compared 16 wild and 16 domestic hooded rats on nondifferential appetitive VI responding, discrimination, and discrimination reversal procedures. The effects of strain, sex, deprivation, preexperimental handling, and sessions on response rate were examined. Performances during the 60 days of VI training showed prolonged increases over that period for all strain-sex groupings, with domestic Ss responding at higher rates than wild. Males also tended to respond at higher rates than females. During the discrimination procedure wild Ss showed more resistance to extinction, although these differences generally diminished after the 30 days of training. During the discrimination reversal procedure domestic Ss reversed their responding pattern more readily, and domestic females reached criterion significantly sooner than domestic males. The effects of deprivation and handling were not significant during the experimental procedures.(20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intramedullary brain stem cyst and trapped IV ventricle after infection with Listeria monocytogenes

We present the rare case of a girl surviving intrauterine listeria brain stem meningoencephalitis, who subsequently developed hydrocephalus, a trapped IV ventricle and an intramedullary cyst. Such cases have been reported only infrequently, and in earlier cases modern imaging studies were not available. Magnetic resonance imaging has been helpful in our patient to delineate the lesions and plan further treatment.     

Natural course of HGV infection in haemophiliacs

The natural course of hepatitis G virus (HGV) infection was clarified in 70 haemophiliacs by testing for HGV RNA and antibodies against HGV envelope protein (anti-E2). None of 12 patients treated with only virus-inactivated coagulation factors were infected with HGV. Of 58 patients who received non-inactivated products, 28 (48%) were positive for HGV RNA and/or anti-E2. Of 16 patients with anti-E2, 14 were negative for the viral RNA, and had recovered from HGV infections. HCV antibodies were detected in 59 patients, and eight patients were successively negative for HCV RNA. Thus, the recovery rate of HGV infection (14/28, 50%) was higher than that of HCV (8/59, 14%) (P<0.001). Longitudinal study revealed that anti-E2 developed either during viraemia or some years after seronegativity for HGV RNA. Hence the antibody response itself seemed not to play a major role in the clearance of HGV though anti-E2 was associated with the clearance of HGV RNA. In conclusion, HGV and HCV are prevalent in patients treated with unsterilized coagulation factor concentrates. However, in contrast to HCV, spontaneous recovery is frequently observed in HGV infections.     

Clozapine and PD149163 elevate prepulse inhibition in Brown Norway rats.

Unmedicated schizophrenia patients exhibit deficits in prepulse inhibition (PPI) of the acoustic startle response. Similar deficits can be induced in rodents via a variety of manipulations and these deficits can be reversed by antipsychotics. Brown Norway (BN) rats exhibit natural PPI deficits under certain parametric conditions. We treated BN rats with haloperidol or clozapine to determine if the BN rat is a useful animal model with predictive validity for the effects of antipsychotics. In addition, we also tested PD149163, a neurotensin-1 receptor agonist, which has been shown to exhibit antipsychotic-like effects in several other animal models. BN rats received subcutaneous injections of either saline or one of two doses of haloperidol (0.5 mg/kg, 1.0 mg/kg), clozapine (7.5 mg/kg, 10 mg/kg) or PD149163 (1.0 mg/kg, 2.0 mg/kg). PPI was measured in startle chambers 30 min after injection. Systemic clozapine and PD149163 but not haloperidol facilitated PPI in BN rats (p     

Pathologic characterization of brown Norway, brown Norway x Fischer 344, and Fischer 344 x brown Norway rats with relation to age

The rat is a common laboratory animal utilized in a variety of investigations including experimental gerontology. Gerontologic investigations can be compromised when the differences observed when comparing young and old animals are actually differences between normal and disease states. It is of critical interest to know the pathology of the animals being studied and to understand the impact of these disease processes on the parameters being measured. The incidence and average age of occurrence for lesions have been characterized and are reported here for one inbred (Brown Norway) and two hybrid strains (Brown Norway x Fischer 344 and Fischer 344 x Brown Norway) of rat. Total lesion incidence functions as a biomaker of aging for all of the strains examined (p < or = .00001). These three genotypes have significantly lower incidence of several major pathologic processes (including glomerulonephritis, retinal atrophy, and leukemia) than do the Fischer 344 and the Wistar rats, two commonly utilized strains. Additionally, the BN and F344 x BN F1 hybrid attain 50% mortality at 130 and 146 weeks of age, respectively, which is significantly greater than the 103 weeks for the F344 rat. It is hoped that access to basic information on these three rat genotypes will increase their utilization by the community of gerontologic scientists.     

Experimental infection with Babesia divergens in cattle persistently infected with bovine virus diarrhoea virus

Nine Norwegian Red cattle, aged 7-14 months, persistently infected with bovine virus diarrhoea virus (BVDV) were inoculated with a Swedish strain of Babesia divergens. Six persistently infected cattle of the same age and breed were kept as controls. Blood and serum samples were collected regularly during the observation period. Rectal temperatures were recorded every morning for 25 days post infection, and the animals were examined clinically on a daily basis. Sera were examined for antibodies to B. divergens by indirect immunofluorescence antibody test (IFAT). Eight of the infected animals developed fever of 2-5 days duration. Babesia divergens organisms appeared in the erythrocytes of all infected animals on the day after inoculation. The parasitaemia lasted for 4-11 days. One animal had a transient haemoglobinuria. Compared with the control group, there was a 20% decrease in the haematocrit. There was a transient lymphopenia and thrombocytopenia during the period of fever. There were no differences in mean numbers of neutrophils between the two persistently infected groups. Compared with cattle free of BVDV, the persistently infected cattle had consistently lower total leucocyte count that was mainly due to decreased mean numbers of neutrophils and monocytes. All infected animals develop antibodies > or = 1:1280 between day 7 and 10 post infection. The magnitude of the antibody response was considerably lower than that of BVDV-free animals inoculated with the same strain and dosage of B.divergens.     

Some determinants of a natural food aversion in Norway rats.

Adult male Long-Evans rats were permitted to feed on the carcasses of adult male rodents, freshly sacrificed by CO? asphyxiation. In a 2-choice preference test (Exp I), hungry Ss were offered 1 conspecific and 1 house mouse, the pair of carcasses being either intact or skinned. 18 Ss offered intact carcasses fed on the mouse or on neither carcass, but 18 Ss offered skinned carcasses fed indiscriminately, usually on both carcasses. In Exp II, 10 hungry Ss that earlier had observed a cagemate feeding on intact conspecific carcasses fed more readily on a similar carcass during a single-choice test than did 8 controls. In Exp II, 20 food-deprived Ss (96 hrs) fed more readily and consumed more tissue from an intact conspecific carcass than did 20 nondeprived Ss. It is concluded that the aversion to feeding on the intact carcass of a freshly sacrificed adult conspecific is deprivation dependent and is mediated by chemoreceptive stimuli from the skin and/or fur. The aversion is diminished by social facilitation. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Crowding and isolation: Determinants of agonistic and food-seeking behavior in Norway rats.

Alternately isolated and crowded 2 groups of 12 male Long-Evans rats. Order of housing and familiarity of the Ss with the test apparatus were also varied systematically. Ss were deprived of food, trained to bar press, and allowed to compete in pairs for sugar water in a Skinner box. Isolated pairs produced more agonistic and contact behaviors and fewer bar presses than did crowded pairs. Weight was found to increase more rapidly during free feeding when animals were isolated. Familiarity of only 1 isolate with the testing environment led to the display of less aggression than was observed in other isolate conditions. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Severe primary HIV-1 infection among black persons in Barbados

The purpose of this long-term follow-up was (1) to investigate disc changes in the olisthetic segment in patients treated conservatively, (2) to compare disc changes above the slipped vertebra in conservatively treated patients with those in operatively treated patients, and (3) to establish possible relations of disc changes to the degree of the slip and to subjective back pain symptoms of the patients. The subjects were 227 patients with isthmic L5 olisthesis diagnosed under 20 years of age (mean 13.8 years) with a mean follow-up of 15.4 (range 5-30) years. Of these, 145 patients had been treated with segmental fusion and 82 had been treated conservatively. At follow-up, standing anteroposterior and lateral radiographs as well as flexion/extension views of the lumbar spine were taken. Disc degeneration was graded semiquantitatively: 0 = normal disc height, 1 = decrease of disc height < 50%, 2 = decrease > or = 50%, and 3 = obliteration of the disc. In the conservatively treated patients degeneration of the olisthetic disc was distributed by grade as follows: O: n = 38, 1: n = 24, 2: n = 14, 3: n = 6. No motion at all was observed in the olisthetic segment in 40 patients (48%) with a mean slip of 30%, segmental motion of 4 degrees-18 degrees was found in 42 patients with a mean slip of 14%. There was a statistically significant association of the degree of slip to the severity of disc degeneration and non-mobility of the segment. Grade 1 degeneration of the L4/5 disc occurred in 25.6% of the conservatively treated patients and in 32% of 48 patients treated with L5-S1 fusion. This correlated with the severity of the slip, but not with pain symptoms or pathologic segmental mobility at the time of follow-up. Out of 84 patients with L4-S1 fusion, in 17% grade 1 degeneration of the L3/4 disc was observed, and 3 out of 13 patients (23%) with L3-S1 fusion had grade 1 degeneration of the disc above the fusion. The disc changes had no correlation with subjective pain symptoms. It is concluded that the natural course of isthmic spondylolisthesis is associated with disc degeneration and spontaneous stabilization of the olisthetic segment. Fusion operations do not significantly increase the rate of disc degeneration in the adjacent disc above the fusion after a mean postoperative follow-up of 13.8 years. No correlation between the number of degenerated discs or the degree of degeneration and subjective low back pain symptoms was found.     

5-oxo-ETE induces pulmonary eosinophilia in an integrin-dependent manner in Brown Norway rats

We have shown previously that the 5-lipoxygenase product 5-oxo-6,8, 11,14-eicosatetraenoic acid (5-oxo-ETE) is a highly potent eosinophil chemoattractant in vitro. To determine whether this substance can induce pulmonary eosinophil infiltration in vivo, it was administered to Brown Norway rats by tracheal insufflation. Eosinophils were then counted in lung sections that had been immunostained with an antibody to eosinophil major basic protein. 5-Oxo-ETE induced a dramatic increase in the numbers of eosinophils (ED50, 2.5 microg) around the walls of the airways, which reached maximal levels (five times control levels) between 15 and 24 h after administration, and then declined. LTB4 also induced pulmonary eosinophil infiltration with a similar ED50 but appeared to be somewhat less effective. In contrast, LTD4 and LTE4 were inactive. 5-Oxo-ETE-induced eosinophilia was unaffected by the LTB4 and PAF antagonists LY255283 and WEB 2170, respectively. However, it was inhibited by approximately 75% by monoclonal antibodies to CD49d (VLA-4) or CD11a (LFA-1) but was not significantly affected by an antibody to CD11b (Mac-1). In conclusion, 5-oxo-ETE induces pulmonary eosinophilia in Brown Norway rats, raising the possibility that it may be a physiological mediator of inflammation in asthma.     

Amelioration of virulent Babesia bovis infection in calves by administration of the nitric oxide synthase inhibitor aminoguanidine

The expression of synaptosomal-associated protein (SNAP-25), neural growth-associated protein (GAP-43) and neural cell adhesion molecule (NCAM) were studied in mouse olfactory cells and axons for 2 weeks following unilateral bulbectomy. The olfactory cells and axons in the control olfactory epithelium were positive for SNAP-25 but levels decreased in the atrophic olfactory epithelium 3 days after bulbectomy. There was no expression of SNAP-25 in the olfactory epithelium on the bulbectomy side 7 days after bulbectomy, indicating that this protein may be a good marker for the degeneration of olfactory cells. The expression of NCAM was still found in the atrophic olfactory epithelium at 7 days after bulbectomy, while the expression of NCAM in the olfactory epithelium of the bulbectomy side was stronger than that on the control side at 14 days after bulbectomy. The expression of GAP-43 in the olfactory axonal bundles of the bulbectomy side at 3 and 4 days after bulbectomy was stronger than that on the control side. These results suggest that upregulation of NCAM may be related to the regeneration of the olfactory cells, with upregulation of GAP-43 probably playing a role in axonal regeneration after bulbectomy.