The pain-relieving effects of lactoferrin on oxaliplatin-induced neuropathic pain

Oxaliplatin (OXL) therapy often causes side effects including chronic peripheral neuropathy. We investigated the pain-relieving effects of recombinant human lactoferrin (rhLf) as well as a long-acting IgG-Fc fused rhLf (rhLf-Fc) on OXL-induced neuropathic pain. We used the hLf in this study, because the homology between mouse Lf and hLf is higher than that of bovine Lf. In addition, rhLf-Fc is expected to enhance the analgesic effect due to the life extension effect in the body. We administered OXL (2 mg/kg, i.v.) to mice twice weekly for 4 weeks. Phosphate buffered saline (PBS), rhLf (100 mg/kg, i.p.) or rhLf-Fc (100 mg/kg, i.p.) was administered once a week from day 15 to 32. We also assessed the continuous infusion of same drugs (10 mg/kg/day) into the external jugular vein by using an osmotic pump. Both of rhLf and rhLf-Fc significantly reduced the hypersensitivity to mechanical stimulation when they were administered intraperitoneally. The continuous infusion of rhLf resulted in a more pronounced effect. Histopathological analysis of sciatic nerve showed that both rhLf and rhLf-Fc tended to reduce nerve fiber damage, but no significant difference was observed in nerve fiber cross-sectional area. Therefore, it was suggested that rhLf or rhLf-Fc injection could be an option for controlling neuropathic pain, which are side effects of OXL.     

Substance P and neurotensin are up-regulated in the lumbar spinal cord of animals with neuropathic pain

Many neuropeptides have been shown to be up-regulated in response to pain. The purpose of this study was to identify pain-related peptides in a rat model of neuropathic pain induced by sciatic nerve cuff implantation. Rats were tested for touch sensitivity prior to and 7 days following cuff implantation or sham surgeries. The lumbar spinal cord was removed on the 8th day post-surgery and the lumbar enlargement was processed for the detection of selected peptides using time-of-flight mass spectrometry. Only substance P (MW 1346.74) and neurotensin (MW 1673.0) were detected in the lumbar spinal cord of animals with mechanical allodynia (P < 0.01) following innocuous tactile stimulation of the affected hind paw. Therefore, substance P and neurotensin may be target candidates for the understanding and treatment of neuropathic pain.     

Early dexamethasone treatment after implantation of a sciatic-nerve cuff decreases the concentration of substance P in the lumbar spinal cord of rats with neuropathic pain

The main purpose of this study was to evaluate the effects of early dexamethasone treatment on pain-related peptides at an early stage in the development of neuropathic pain induced by implantation of a sciatic nerve cuff in Sprague Dawley rats (body weight 250 to 350 g). The rats were tested for touch sensitivity with the use of von Frey filaments before and 3 d after cuff implantation (n = 12) or sham surgery (n = 6). Half of the cuff-implanted rats received dexamethasone, 1 mg/kg intraperitoneally, 1 h after surgery. Spinal cords were collected on the 3rd day after surgery, and the lumbar enlargement was processed for the detection of selected peptides (neurotensin, substance P, cholecystokinin [CCK], vasoactive intestinal peptide, and calcitonin gene-related peptide) by means of liquid chromatography and tandem mass spectrometry. The right sciatic nerve of each rat was collected, fixed, and stained for histopathological evaluation. Except for neurotensin, all the peptides showed an increased concentration with neuropathic pain; however, the differences were significant (P < 0.05) only for substance P and CCK. In the animals treated with dexamethasone, mechanical allodynia was less pronounced (P < 0.01), and only the concentration of substance P was decreased significantly (P < 0.05). Sciatic nerve sections showed a decrease in C (P < 0.01) and Adelta (P < 0.03) fibres with neuropathic pain and a nearly normal percentage of C fibres after dexamethasone treatment. The dexamethasone-treated animals also had less inflammation detectable microscopically at the nerve constriction site compared with cuff-implanted animals that were not treated with dexamethasone. Our results suggest that in the early stages of neuropathic pain induced by an inflammatory process, dexamethasone may be a useful treatment and that substance P plays an important role in pain perception.     

Liposome-encapsulated oxymorphone prevents hyperalgesia for 7 days in a rat model of neuropathic pain

A delayed‐release formulation of liposome‐encapsulated oxymorphone (LEO) was produced using a novel dehydration–rehydration technique. Preparations were standardized spectrophotometrically against a known concentration of the drug. The purpose of this study was to test the analgesic properties of LEO in a rat model of neuropathic pain. Sprague–Dawley rats were divided into control (non‐neuropathic) and test (neuropathic) groups. Control and test groups were administered one SC injection of (i) vehicle liposomes (negative control treatment); (ii) liposome‐encapsulated morphine, 2.8 mg kg^?1 (positive control treatment); or (iii) LEO, 1.2 mg kg^?1. All treatments were administered after baseline thermal withdrawal latencies (TWL) were determined (9.2 ± 0.39 seconds (mean ± SEM)). Test groups then underwent sciatic ligation to induce neuropathic pain. TWL were determined in all six groups (n = 8) daily for 1 week. In a separate group of age‐matched rats, blood (0.3 mL from the jugular vein) and urine (1–2 mL via metabolism cages) were collected daily for 7 days after administration of LEO (1.2 mg kg^?1). TWL did not change in the control rats given liposome‐encapsulated sucrose or morphine. There was a small increase (p = 0.04) in TWL in control rats given LEO, likely as a result of the relatively higher dose of oxymorphone compared with morphine based on receptor affinity. TWL in test rats given blank liposomes decreased significantly (p < 0.001) by day 4 (7.1 ± 0.5 seconds), with a maximal decrease by day 7 (5.1 ± 0.36 seconds), indicating development of full hyperalgesia. In contrast, rats given liposome‐encapsulated morphine or oxymorphone had no change in TWL at day 4, indicating that these preparations prevented hyperalgesia after a single injection. This treatment effect persisted through day 7. Serum concentrations of oxymorphone after a single injection of LEO peaked at 4 hours (6.8 ± 0.82 ng mL^?1) and were detectable through day 4 (0.98 ± 0.003 ng mL^?1), while urine concentrations of drug were detectable through day 7. This result suggests that oxymorphone metabolites might have been responsible for the protracted analgesic response. The encapsulation efficiency of oxymorphone using this novel technique was approximately 96%. In conclusion, liposome encapsulation of oxymorphone proved to be an efficient mechanism to provide a delayed‐release formulation of this opioid. This single dose of subcutaneously administered liposome‐encapsulated oxymorphone was effective in preventing hyperalgesia for 7 days in this animal model of neuropathic pain.     

Effect of prostaglandin F2α administration on uterine polymorphonuclear neutrophil counts in Japanese heavy draft horses

The objective of this study was to examine the effect of prostaglandin F2_α (dinoprost) and oxytocin administration on uterine polymorphonuclear neutrophil counts in the Japanese heavy draft mare. To compare polymorphonuclear neutrophil (PMN) counts in the endometrium, a total of 162 samples were collected from 54 estruses of 47 mares (before ovulation, day 0, and day 2) using a double-guarded cytology brush. Dinoprost (PG; 5 mg) was administered intramuscularly (i.m.) only once, on day 0, whereas oxytocin (OT; 20 U i.m.) was administered three times at 12-hr intervals starting on day 0. The plasma progesterone concentrations from days 0 to 14 were not different between the non-treatment (CON), PG treatment, and OT treatment groups. The PMN counts increased in all the groups from before administration to day 0 (CON, 0.90 to 3.55; PG, 1.20 to 8.45; and OT, 0.70 to 1.70; P=0.0014, 0.0046, and 0.0073, respectively). There was a significant decrease in PMNs from day 0 to day 2 only in the PG group (P=0.0073). The pregnancy rate was not different among the CON (12/18), PG (14/18), and OT (10/18) groups. The results of this study indicate that dinoprost can reduce uterine polymorphonuclear neutrophil counts.     

Pathology and Neurotoxicity in Dogs after Repeat Dose Exposure to a Serotonin 5-HT1B Inhibitor

AZD3783, a cationic amphiphilic drug and a potent inhibitor of the 5-hydroxytryptamine (5-HT_1B) receptor, was explored as a potential treatment for depression. To support clinical trials, repeat dose toxicity studies in rats and dogs were conducted. Here we report toxicity findings in dogs after dosing from 1 to 3 months. In the 1-month study, there were minimal neuronal vacuolation in the brain, a marked increase in liver enzymes accompanied by hepatocellular degeneration/necrosis and phospholipidosis (PLD), and PLD/cholecystitis in the gallbladder of animals dosed at 47 mg/kg/day. In the 3-month study, neurotoxicity resulted in euthanasia of one animal dosed at 30 mg/kg/day after 86 days. Extensive pathologic changes were seen in all animals in retina epithelium (inclusion bodies), brain (neuronal vacuolation, degeneration, or necrosis and nerve fiber degeneration), spinal ganglia (vacuolation, degeneration, or necrosis), as well as sciatic and optic nerves (degeneration). Pigment-laden macrophages were observed in the lung, kidney, liver, gallbladder, bone marrow, gastrointestinal tract, and lymphoid tissues. Also seen were vitrel and retinal hemorrhage in the eyes. A brain concentration and pathology study showed that the concentration of AZD3783 in the brain was approximately 4 times higher than in the plasma after 4 weeks of dosing, however, they were similar in all regions examined, and did not correlate with areas with pathologic findings. Our findings with AZD3783 in dogs have not been reported previously with other CNS compounds that effect through serotonergic pharmacology.     

Ultrasound-guided block of the feline sciatic nerve

This study was conducted to validate an ultrasound-guided technique to block the sciatic nerve in cats. An anatomical study was first carried out in four feline cadavers to evaluate the feasibility of the glutea (cranial and caudal), femoris and poplitea ultrasonographical approaches for the sciatic nerve block. The results showed that the femoris approach was optimal because the region was free of vascular and bony structures, and the needle was easily visualised in-plane. Then, the efficacy of the femoris ultrasonographical approach to block the sciatic nerve was tested in six healthy adult experimental cats. A dose of 2 mg/kg lidocaine 2% diluted in saline to a final volume of 1 ml was administered in all cats. The blockade was successful in all cases and the cats recovered uneventfully. This study shows the usefulness of the femoris approach in performing an ultrasound-guided blockade of the sciatic nerve in cats.     

Digoxin-quinidine interaction in the dog

In seven healthy dogs, digoxin was given as an oral loading dose (0.05 mg/kg/day) on the first day, followed by an oral maintenance dose (0.02 mg/kg/day) during the next 14 days. On the sixth day of digoxin treatment, oral quinidine (200 mg b.i.d.) was added until the tenth day. Plasma concentrations of digoxin and quinidine were measured; in three of the seven dogs ECG and physical signs of digitalis toxicity were evaluated. The average steady state plasma concentration of digoxin increased significantly ( P <0.01) during quinidine administration (from 1.4 to 2.3 ng/ml). On the days that digoxin was administered without quinidine, none of the dogs vomited nor was anorectic; the PQ-interval increased significantly ( P <0.01) between 0.01 and 0.03 s. When quinidine was added, vomiting and anorexia occurred but no further increases in die PQ-interval were seen.     

Effect of β‐carotene on health status and performance of sows and their litters

A total of 48 sows were allocated to four groups (12 sows per group) at the 99th day of pregnancy and were treated throughout two consecutive breeding cycles, as follows: (a) control group: no treatment; (b) group BC1: 400 mg β‐carotene/sow/day via feed from 7 days prior to the expected farrowing, until the 30th day postservice; (c) group BC2: 400 mg β‐carotene/sow/day via feed from 7 days before weaning up to service, followed by 200 mg β‐carotene until the 30th day postservice; and (d) group BC inj: four intramuscular (i.m.) injections of 200 mg β‐carotene/sow (on the 100th day of pregnancy, on the day of farrowing, on the day of weaning and on the first day of oestrus). Serum β‐carotene equivalents, vitamin A and IgG concentrations were determined in sows at several times of the breeding cycle. Moreover, serum IgG concentrations were determined in piglets on the second day of lactation and at weaning. Data relating to sow reproductive parameters and litter parameters were also recorded. It was shown that concentrations of serum β‐carotene equivalents were elevated only in the BC inj group during lactation and at service, while serum vitamin A concentrations were also elevated in the BC inj group only at oestrus. There was no effect of β‐carotene on the oestrus intensity score, the weaning‐to‐oestrus interval, the number of returns to oestrus per sow and the farrowing‐to‐farrowing interval. The number of piglets born alive was greater in the BC inj group compared with the controls, while the litter size at weaning was greater in the groups BC1, BC2 and BC inj compared with the control group (p < 0.05). Supplementation of β‐carotene did not appear to influence the serum IgG concentration in sows and piglets.     

Indices of non-specific and specific humoral immunity in pigs immunomodulated with the Bioimmuno preparation and/or immunised with the Respisure One vaccine against mycoplasmal pneumonia of swine

The purpose of the study was to determine the influence of the Bioimmuno preparation administered in feed and/or immunisation with the Respisure One vaccine on the development of selected indices of non-specific and specific humoral immune response against Mycoplasma hyopneumoniae (Mhp) infections in pigs. The study was performed on 28 piglets at the age of 4 weeks, divided into four equal groups. The biopreparations were administered according to the following pattern: group I--Bioimmuno (IFI Olsztyn, Poland) with feedstuff at amount of 1 kg/50 kg of feed for 48 h before vaccination with Respisure One (Pfizer) on day 28 of life; group II--Bioimmuno only (1 kg/50 kg feedstuff) for 48 h before vaccination with Respisure One of groups I and III; group III--Respisure One only on day 28 of life (2 ml/animal i.m.) and group C (control)--PBS (2 ml/animal i.m.) simultaneously with vaccination of groups I and III. On days 0, 3, 7, 14 and 21 after immunomodulation and/or immunisation, the serum level of gamma-globulins, the activity of lysozyme (LSM) as well as the serum levels of cytokines: interferon gamma (IFNgamma), interleukin 1 beta (IL-1beta) and interleukin 6 (IL-6) were determined, as indices of non-specific immune response against Mhp infections in pigs. The study has revealed that in piglets after weaning the application of the Bioimmuno and/or Respisure One biopreparations improves the non-specific immunity parameters stimulating an increase in serum levels of gamma-globulins, lysozyme and cytokines (IFNgamma, IL-1beta, IL-6), while late appearing seroconversion confirms a minor role of specific humoral immunity in the protection against Mhp infection.     

Measurement of isotype-specific antibody responses to Aujeszky's disease virus in sera and mucosal secretions of pigs.

Enzyme-linked immunosorbent assays (ELISAs) for the detection of porcine IgM, IgA, IgG1 and IgG2 antibodies directed against Aujeszky's disease virus (ADV) are described. ADV-specific IgA and IgM were detected in an antibody capture assay, and ADV-specific IgG1 and IgG2 were detected in an indirect double antibody sandwich assay. A selected set of samples was tested in the four ELISAs and in a 24 h virus neutralization assay. Comparison of the results showed that the ELISAs were isotype-specific, sensitive, and reproducible. Samples with ADV antibody of one isotype showed that ADV-specific IgG1, IgG2 and IgM were able to neutralize the virus in vitro. In vitro neutralization of virus can be enhanced by complement. ADV-specific IgA neutralized virus only weakly. ADV-infected cells activated complement in the absence of antibody. Specific IgG2 and IgM enhanced complement activation. Analysis of the time course of antibody responses after infection or vaccination revealed that the isotype-specific ELISAs are suitable to study the humoral antibody response of pigs to the virus in mucosal secretions. Wild-type virus (strain NIA-3) and an attenuated vaccine strain (Bartha) administered intranasally induced mucosal IgM and IgA responses to the virus. In contrast, a killed vaccine (Nobivac) administered intramuscularly induced only weak mucosal IgM responses. The attenuated vaccine strain primed for a mucosal IgA memory response evoked upon challenge infection with wild-type virus.     

Induction of cell proliferation in the rat liver by the short-term administration of ethyl tertiary-butyl ether

In the present study, in continuation of our previous experiment in order to investigate the mode of action (MOA) of ethyl tertiary-butyl ether (ETBE) hepatotumorigenicity in rats, we aimed to examine alterations in cell proliferation, that are induced by short-term administration of ETBE. F344 rats were administered ETBE at doses of 0, and 1,000 mg/kg body weight twice a day by gavage for 3, 10, 17 and 28 days. It was found that the previously observed significant increase of P450 total content and hydroxyl radical levels after 7 days of ETBE administration, and 8-OHdG formation at day 14, accompanied by accumulation of CYP2B1/2B2, CYP3A1/3A2, CYP2C6, CYP2E1 and CYP1A1 and downregulation of DNA oxoguanine glycosylase 1, was preceded by induction of cell proliferation at day 3. Furthermore, we observed an increase in regenerative cell proliferation as a result of ETBE treatment at day 28, followed by induction of cell cycle arrest and apoptosis by day 14. These results indicated that short-term administration of ETBE led to a significant early increase in cell proliferation activity associated with induction of oxidative stress, and to a regenerative cell proliferation as an adaptive response, which could contribute to the hepatotumorigenicity of ETBE in rats.     

Innate immune response of mammary gland induced by intramammary infusion of Bifidobacterium breve in lactating dairy cows

This study aimed to evaluate innate immune responses of mammary glands induced by intramammary infusion of Bifidobacterium breve in dairy cows. Somatic cell counts in quarters of cows showed a marked increase following B. breve infusion on days 1 and 2. Opsonized-stimulated chemiluminescence response in quarter milk was significantly (P<0.05) increased by B. breve infusion on days 1 to 3 compared to that of pre-infusion. Lactoferrin concentrations in B. breve-infused quarter milk increased significantly (P<0.05) on days 2 to 4 and 6 compared to those of pre-infusion. IgG and IgA concentrations in B. breve-infused quarters significantly (P<0.05) increased on days 2 to 4 for IgG and days 3, 4, 6 and 8 for IgA compared to those of pre-infusion. Interleukin (IL)-1β and IL-8 mRNA levels in somatic cells from B. breve-infused quarters were significantly (P<0.05) upregulated on day 1 compared to those on days 0 and 14. Conversely, IL-6 mRNA levels in somatic cells from B. breve-infused quarters on days 0, 1 and 14 and NF-κB mRNA levels on day 0 were significantly (P<0.05) down-regulated compared to those of control. IL-1β, tumor necrosis factor (TNF)-α and IL-6 concentrations increased on days 1, 3 and 7 after B. breve infusion in quarters. Intramammary infusion of B. breve (3 × 10⁹ cfu) induces a massive influx of leukocytes and enhances innate immune response in mammary glands. This event may contribute to the enhancing host defense in the mammary gland.     

Neurotoxicity induced by a single oral dose of aniline in rats.

The neurotoxicity of aniline and its age-dependent responses were investigated in male rats. Groups of 6 rats, 4-week-old, were treated once with aniline (500, 750 or 1,000 mg/kg) or olive oil by gavage. Additional groups of 6 rats, 7- or 10-week-old, were treated once with 800 mg/kg of aniline or olive oil. Paralytic gait or hindlimb paralysis was observed between post-treatment days 8 and 15 in two out of six rats receiving 1,000 mg/kg of aniline at 4 weeks of age. On post-treatment day 15, spongy change in the white matter of the spinal cord was observed in all rats receiving 750 or 1,000 mg/kg of aniline at 4 weeks of age. The lateral and ventral columns of the thoracic spinal cord were the most severely affected. Spongy change in the facial nerve and spinal trigeminal tracts of pons and medulla oblongata, and mild degeneration of the peripheral nerves was found in 3 out of 6 rats receiving 1,000 mg/kg of aniline. At the ultrastructural level, the spongy change was due to distention of the myelin sheath and splitting of the intraperiod line. Axons were well preserved in the affected nerve fibers. No abnormalities were seen in the neuronal cell bodies. Although transient cyanosis was observed in all rats receiving 800 mg/kg of aniline at 7- or 10-week-old, as well as in rats receiving 750 or 1,000 mg/kg of aniline at 4-week-old, no treatment-related neurobehavioral or morphologic abnormalities were found in the former. These findings demonstrate the neurotoxicity of orally administered aniline for rats, depending upon the age of the animal at the time of administration.     

Evaluation of IgG concentration and IgG subisotypes in foals with complete or partial failure of passive transfer after administration of intravenous serum or plasma.

The purpose of this study was to evaluate the ability of an equine plasma product i.v. and a concentrated serum product i.v. to deliver antibodies to 46 foals with failure of passive transfer (FPT). Treatment of FPT was as per manufacturers recommendations, using plasma (950 ml/unit) or a concentrated serum product (250 ml/unit). Significant variables affecting the 3 day post-transfusion serum immunoglobulin G (IgG) concentration of foals included body weight, pretransfusion IgG concentration, number of product units transfused, foaling season and product administered. Plasma treatment had a greater increase in post-transfusion serum IgG concentrations compared to the serum product treatment mainly because plasma contained approximately twice the amount of IgG per unit as the serum product. The change in equine influenza virus and tetanus toxoid-specific IgGa, IgGb, and IgG(T) titres was measured in foals from pretransfusion to 3 days post-transfusion. For each gram of IgG transfused, the change in antigen-specific IgG subisotypes were similar for both treatment groups. The results of this study suggest that similar foal serum IgG concentrations can be achieved 3 days post-transfusion by administering 1 unit of plasma or 2-3 units of serum product.     

坐骨神经内神经诱向因子的制备与表达

用聚丙烯酰胺凝胶电泳在坐骨神经损伤侧远端提取具有神经诱向生长作用的18kDa蛋白作为抗原，通过免疫BALB／C小鼠，经杂交瘤技术与ELISA法筛选，获取稳定分泌单克隆抗体的杂交瘤细胞株。免疫组织化学法和计算机图像处理系统显示：生后1，3，7，14，21和28日龄大鼠坐骨神经中18kDa蛋白免疫反应的分布，此分布随年龄发育而逐渐减弱。     

Development of immunocompetence of broiler chickens

Subpopulations of T-cells, B-cells, macrophages and ellipsoid-associated reticular cells (EARC) could be demonstrated by immunohistochemical staining early in the development of chicken spleen. However, the typical structures of the spleen, such as the peri-arteriolar lymphoid sheath (PALS) and the ellipsoids with their surrounding ring of macrophages, were only formed around embryonic day (ED) 20. These structures and especially the B-cell compartment, i.e., the peri-ellipsoid lymphoid sheath (PELS) gradually matured during the first week posthatch.

Therefore, we analysed at what age broiler chickens could generate a humoral response against the thymus-dependent antigen bovine serum albumin (BSA). Chickens were immunised in ovo (ED16 and ED18) and at 1, 7 and 12 days of age and subsequent BSA-specific immunoglobulin (Ig) M and IgG responses were measured up to 10 days postimmunisation (DPI). No major differences were observed in the relative growth rates, while hatchability was only slightly reduced. Only in chicks immunised on 12 days of age, IgM and IgG responses were high with a normal kinetic pattern. In chicks immunised on 7 days of age, responses were just detectable, but they were absent in chicks immunised in ovo and on the day of hatching (Day 1).

In a subsequent experiment, 1-, 7- and 12-day-old chicks were BSA-immunised and Ig responses were measured for a longer period up to the age of 28 days. The IgG response of chicks immunised at 1 day of age was lower and occurred later (from 28 DPI) than the response of chicks immunised at 7 and 14 days of age (from 14 DPI). It was not increased by a booster immunisation on 29 days of age, in contrast to the response of chicks immunised at 7 and 14 days of age. These findings indicate that vaccination at 1 day of age does not activate the B-cell response resulting in antibody production and support the idea that the immune function of the late embryonic and neonatal chickens is not entirely developed due to the incomplete structural organisation of their secondary immune organs.     

Immunostimulating and growth-promoting effects of sugar cane extract (SCE) in chickens

Polymorphonuclear cells of the peripheral blood in the chicken significantly increased their phagocytosis when cultured with sugar cane extract (SCE; 250-1,000 microg/ml) for 24 hr. Chickens orally administered SCE (500 mg/kg/day) for 3 or 6 consecutive days at 1 week of age showed significantly higher body weight and gain in body weight/day and a lower food conversion ratio within the growing period of 6 weeks than physiological saline-administered control chickens. Furthermore, oral administration of SCE also resulted in significantly higher immune responses against sheep red blood cells and Brucella abortus. These results suggest that SCE has immunostimulating and growth promoting effects in chickens.     

Intrapreputial infection of young bulls with bovine herpesvirus type 1.2 (BHV-1.2): acute balanoposthitis, latent infection and detection of viral DNA in regional neural and non-neural tissues 50 days after experimental reactivation

Venereal infection of bulls with bovine herpesvirus type 1.2 (BHV-1.2) may result in acute balanoposthitis followed by the establishment of latent infection, presumably in dorsal root nerve ganglia. We herein report the characterization of the acute and latent infection of young bulls with a Brazilian BHV-1.2 isolate and the investigation of neural and non-neural sites in which viral DNA persists during latent infection, i.e. 110 days after inoculation and 50 days after experimental reactivation. Intrapreputial inoculation of BHV-1.2 isolate SV-56/90 (10(6.5)pfu per animal) resulted in severe balanoposthitis, characterized by redness of the penis and preputial mucosa, coalescent vesicles and fibrinous exsudate in all four infected bulls. Virus shedding was detected in preputial secretions and semen up to days 14 and 13 pi, respectively. Dexamethasone administration at day 60 pi led to reactivation of the infection in all animals, resulting in virus shedding in preputial secretions and/or in semen. At day 50 post-reactivation (pr), the animals were euthanized and regional tissues were collected for PCR and virus isolation. Viral DNA was consistently detected in the dorsal root ganglia of nerves genito-femoral (4/4) and obturator (4/4); frequently in the pudendal (3/4), sciatic (3/4) and rectal caudal nerve ganglia (2/3). In addition, viral DNA was detected in the pelvic sympathetic plexus of one bull and in regional lymph nodes (deep inguinal (2/4); sacral (1/4); medial iliac (1/4)) of two bulls. No infectious virus could be recovered from homogenates of DNA positive tissues, indicating the absence of actively replicating virus. These results demonstrate that BHV-1.2 DNA may persist in several sacral nerve ganglia and in regional lymph nodes as well during latent infection, i.e. 50 days after experimental reactivation. These findings may help in understanding the pathogenesis of acute and latent genital infection by BHV-1.2.     

Experimentally induced infection of cats with Borrelia burgdorferi.

To determine whether cats could be infected experimentally with Borrelia burgdorferi, 15 cats were inoculated with approximately 1,000 B burgdorferi. Seven cats were inoculated by the IV route, 2 by the oral route, 2 by the ocular route, and 4 by the oral-ocular route. Six control cats were inoculated with phosphate-buffered saline solution by the IV, oral, and ocular routes. Prior to the start of the study, all 21 cats were seronegative for B burgdorferi on the basis of results of the indirect fluorescent antibody (IFA) test, and their blood was B burgdorferi culture negative. All of the IV, orally, and ocularly inoculated cats developed IgG antibodies to B burgdorferi as detected by IFA testing. Of 4 oral-ocularly inoculated cats, 2 developed IFA-detectable antibodies and the remaining 2 cats developed low-titer response (1:128) on postinoculation (PI) day 10 only. All control cats remained seronegative. The organism was detected in blood smears from 2 of the IV inoculated cats on PI days 10 and 24 and from 2 oral-ocularly infected cats, 1 on PI days 17 and 24 and 1 on PI day 10. Spirochetes were not detected in the blood after PI day 24. The organism was isolated from tissues of only 1 cat (the lung of an ocularly inoculated cat necropsied at 7 months after inoculation). Spirochetes were not isolated from control cats. Neither clinical signs of infection nor gross or histologic abnormalities were found in any of the inoculated or control cats. Results indicate that cats are susceptible to infection with B burgdorferi, but clinically apparent disease may not be common.