Effects of an extract of Serenoa repens on dogs with hyperplasia of the prostate gland.

OBJECTIVE: To determine effects of an extract of Serenoa repens on dogs with prostatic hyperplasia. ANIMALS: 20 mature male dogs with benign prostatic hyperplasia. PROCEDURE: Dogs were assigned to 3 comparable groups on the basis of prostatic volume per kg of body weight and degree of prostatic hyperplasia determined histologically. Dogs in 2 groups were treated for 91 days (8 received 500 mg, PO, q 8 h [1,500 mg/d], and 6 received 100 mg, PO, q 8 h [300 mg/d]). The control group of 6 dogs did not receive medication. Effects of treatment on prostatic volume, prostatic weight, prostatic histologic characteristics, radiographic and ultrasonographic assessment of prostatic size, results of CBC, serum biochemical analyses, and urinalysis, serum testosterone concentration, and semen characteristics were determined. At the termination of the study, all dogs were euthanatized, and necropsies were performed. Investigators conducting tests and interpreting results were not aware of treatment group of each dog. RESULTS: Treatment did not affect prostatic weight, prostatic volume, or prostatic histologic scores, libido, semen characteristics, radiographs of the caudal portion of the abdomen, prostatic ultrasonographs, or serum testosterone concentrations. Results of CBC, serum biochemical analyses or urinalysis, and body weights did not change during treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with an extract of S repens for 91 days did not significantly affect the prostate gland of dogs. Adverse effects were not evident. Although products containing extracts of S repens are widely advertised for men with prostatic hyperplasia, beneficial or harmful effects of this plant extract were not found in dogs with prostatic hyperplasia.

Effects of dietary polyunsaturated fatty acid supplementation in early renal insufficiency in dogs.

Dietary supplementation with polyunsaturated fatty acids (PUFAs) alters the course of experimental kidney disease in dogs. In particular, supplementation with omega-6 PUFAs hastens the decline of kidney function, and omega-3 PUFAs are renoprotective. We investigated the early stages of renal insufficiency to determine whether PUFA supplementation altered the magnitude of hypercholesterolemia or glomerular hemodynamics. Two months after 11/12 nephrectomy, dogs were randomly divided into three groups of 6 animals each. Each group of dogs was then fed a low-fat basal diet supplemented with one of three sources of lipid to achieve a final concentration of 15% added fat. Fat sources were rich in omega-3 PUFAs (menhaden fish oil, group FO), omega-6 PUFAs (safflower oil, group SO), or saturated fatty acids (beef tallow, group C). Early in renal insufficiency, before significant kidney damage, group FO had a lower (P<.05) serum cholesterol concentration and tended to have a lower urinary prostaglandin E2 (PGE2) and thromboxane A2 (TxA2) excretion than group C. In contrast, group SO had a higher mean glomerular capillary pressure (P<.05) and more glomerular enlargement (P<.05) and tended to have higher eicosanoid excretion rates than group C. These differences in lipid metabolism, glomerular hypertension and hypertrophy, and urinary eicosanoid metabolism could explain, in part, the beneficial effects of omega-3 PUFAs and the detrimental effects of omega-6 PUFAs when administered on a long-term basis in this model of renal insufficiency.

Progression of chronic renal disease in the dog.

Progressive loss of nephron function may be caused by persistence of factors that initiated renal disease. However, newer studies suggest that nephron damage is self-perpetuating once renal mass is reduced to some critical level. Original theories on mechanisms of self-perpetuated nephron injury focused on intraglomerular hypertension and glomerular hypertrophy, but several other factors have now been incriminated, including tubulointerstitial responses, proteinuria, and oxidative stress. Studies of dogs with surgically reduced renal mass (remnant kidney model of chronic renal disease) have allowed investigation of the self-progression theory in this species. Use of this model eliminates pre-existing renal disease as a confounding factor. Data from these studies indicate that self-perpetuated renal injury is initiated when mild azotemia is induced (plasma creatinine concentration = 2 to 4 mg/dL). Thus, with naturally occurring renal disease(s), it is likely that self-perpetuated nephron damage is occurring before or at the time when most cases of chronic renal disease are diagnosed. In dogs with remnant kidneys, loss of renal function often occurs at a linear rate over time, but non-linear patterns are common as well. The reciprocal of plasma creatinine concentration, which has been used to monitor rate of progression, is only a fair marker of renal function when compared to GFR. Thus, clinical results from creatinine measurements on cases of naturally occurring disease should not be interpreted too stringently. In remnant kidney dogs, the magnitude of proteinuria (UPC ratio) was not predictive of the rate in decline of GFR, casting doubt on importance of proteinuria in causing progression of renal disease. However, progressive increases in UPC may be a marker of an accelerated rate of renal injury. Self-perpetuation of renal injury in dogs could be the sole mechanism by which naturally occurring renal diseases progress. When more information is available on the rate of progression of naturally occurring diseases, it may become apparent whether factors initially inciting renal damage have an additive effect on rate of progression.

Beneficial effects of chronic administration of dietary omega-3 polyunsaturated fatty acids in dogs with renal insufficiency.

Dietary supplementation with polyunsaturated fatty acids (PUFA) alters the course of experimental renal disease in rats. However, chronic renal disease in other laboratory animals and in human beings frequently responds differently to experimental manipulations. We investigated the effects of variations in dietary PUFA composition on the chronic course of induced renal disease in dogs. Two months after 15/16 nephrectomy, dogs were randomly divided into three groups of seven animals each. For the next 20 months, each group of dogs was fed a low-fat basal diet supplemented with one of three sources of lipid to achieve a final concentration of 15% added fat. Fat sources provided omega-3 PUFA (menhaden fish oil, group FO), omega-6 PUFA (safflower oil, group SO), or saturated fatty acids (beef tallow, group BT). Throughout the dietary trial, the magnitude of proteinuria and the plasma concentrations of creatinine, cholesterol, and triglyceride were lower in group FO. The mean overall glomerular filtration rate was 0.89+/-0.18 ml/min per kilogram of body weight in group SO, a value that was significantly less (p < 0.05) than the corresponding values for groups BT and FO (1.21+/-0.18 and 1.43+/-0.20 ml/min/kg, respectively). Renal interstitial fibrosis also was significantly elevated in group SO. The extents of mesangial matrix expansion, glomerulosclerosis, and renal interstitial cellular infiltrate were similar in groups BT and SO, but lower (p < 0.05) in group FO. We conclude that supplementation with omega-6 PUFA enhanced renal injury; supplementation with omega-3 PUFA was renoprotective.

Protein and calorie effects on progression of induced chronic renal failure in cats.

OBJECTIVE: To determine effects of dietary protein and calories on progression of induced chronic renal failure in cats. ANIMALS: 28 young adult female cats. PROCEDURE: Renal mass was reduced surgically, and glomerular filtration rate (GFR) was determined. Cats were alloted to 4 groups of 7 with similar mean GFR (1.52 to 1.55 ml/min/kg of body weight). Diets were formulated to provide: low protein and calorie (diet A), low protein and high calorie (diet B), high protein and low calorie (diet C), and high protein and calorie (diet D) intakes. Cats were fed their prescribed diet for 12 months, then blood and urine biochemical variables were measured, after which kidney specimens were examined microscopically. RESULTS: Protein intake by cats of groups C and D (9.0 g/d/kg) was substantially greater than that by cats of groups A and B (5.3 and 5.2 g/d/kg, respectively). Caloric intake by cats of groups B and D (73 and 71 calories/d/kg, respectively) was greater than that by cats of groups A and C (58 and 55 calories/d/kg, respectively). Renal glomerular lesions were mild and not affected by protein, calories or their interactions. Nonglomerular lesions, though mild, were significantly influenced by calorie intake, but not by protein or calorie-protein interactions. The GFR did not decrease in any group. Urine protein-to-creatinine ratio increased significantly in all groups after reduction of renal mass, but values from all groups remained within the reference range (0 to 0.3). CONCLUSIONS AND CLINICAL RELEVANCE: Diets replete in protein were not associated with increased severity of glomerular or nonglomerular renal lesions, increased proteinuria, or decreased GFR. Diets replete in calories were not associated with increased severity of glomerular lesions, but were associated with mild increase of nonglomerular lesions. Factors other than protein and calorie intake must be considered potential causes of progression of renal failure in cats. Results raise questions about the practice of restricting quantity of protein in the diet of cats with chronic renal failure, with the intention of ameliorating development of further renal damage.

Pathophysiology and management of progressive renal disease.

Recently, the hypothesis that all renal diseases are inherently progressive and self-perpetuating has focused attention on adaptive changes in renal structure and function that occur whenever renal function is reduced. These glomerular adaptations to renal disease include increases in filtration rate, capillary pressure and size, and are referred to as glomerular hyperfiltration, glomerular hypertension and glomerular hypertrophy, respectively. Extrarenal changes, such as dietary phosphate excess, systemic hypertension, hyperlipidaemia, acidosis and hyperparathyroidism occur in animals with renal disease and may be contributors to progression of renal disease. Emphasis in the management of companion animals with renal disease has shifted to identifying, understanding and controlling those processes that play a role in the progression from early to end-stage renal failure. Advances made by veterinary nephrologists in the past 15 years permit resolution of old controversies, formulation of new hypotheses and discussion of unresolved issues about the nature of progressive renal disease in dogs and cats.

Use of partial prostatectomy for treatment of prostatic abscesses and cysts in dogs.

OBJECTIVE: To determine whether dogs had prostatic disease, urinary incontinence, or urinary tract infection 1 year after partial prostatectomy to treat prostatic abscesses and cysts. DESIGN: Prospective study. ANIMALS: 20 male dogs with prostatic abscesses or cysts. Fifteen dogs had evidence of urinary tract infection. Only 8 dogs urinated normally; the remainder dribbled, had obstructions, or required medical treatment. PROCEDURE: Partial prostatectomy was performed on each dog. Sexually intact dogs (n = 12) also were castrated. RESULTS: None of the dogs had return of prostatic cystic enlargement or clinical signs of prostatic disease during the first year after surgery. Two dogs were euthanatized within 1 year after surgery, with 1 dog having prostatic enlargement and adenocarcinoma and 1 dog having unrelated lymphosarcoma. Fifteen dogs were continent. The remaining 5 dogs urinated normally but had intermittent and minor incontinence. Eleven dogs had no signs of infection 1 year after surgery, 5 had pyuria or positive urine bacteriologic culture results, 2 did not have urinalysis performed, and 2 were euthanatized. CLINICAL IMPLICATIONS: Dogs with severe prostatic abscesses or cysts and infections can be successfully treated by partial prostatectomy with an ultrasonic surgical aspirator and castration, resulting in long-term disease resolution. Although most dogs with severe prostatic disease do not urinate normally before surgery, nearly all dogs resume normal micturition after partial prostatectomy. Postoperative results of partial prostatectomy appear to be better than those of previous drainage techniques for treatment of prostatic cavitary disease.

Effects of parathyroidectomy on induced renal failure in dogs.

OBJECTIVE: To determine the effects of parathyroid hormone (PTH) depletion on dogs with induced chronic renal failure. ANIMALS: 2 groups of 26 mixed-breed dogs of both sexes (13 were parathyroidectomized [PTX] and 13 had sham surgery). PROCEDURE: After surgical reduction of renal mass and PTX, dogs were selected for a 24-month period of study and monitored for clinical, hematologic, blood biochemical, and organ function status. On development of uremia or after 24 months, dogs were euthanatized, and tissues were examined. RESULTS: Higher survival rate and smaller decrement in renal function (glomerular filtration rate) were observed in PTX dogs, compared with those that had sham surgery, but values did not reach statistical significance. The PTX dogs remained hypocalcemic during the study and had lower serum Ca2+ X P product values. Regardless of parathyroid state, survivors and fatalities could be separated on the basis of serum Ca2+ X P product values. Parathyroidectomy did not prevent renal deposition of calcium, and renal lesions were poorly correlated with renal cortical calcium concentration. Abnormalities reported in dogs with renal failure, which were attributed to PTH (glucose intolerance, pulmonary hypertension), were not observed in PTX dogs or those that had sham surgery. CONCLUSIONS AND CLINICAL RELEVANCE: PTX had beneficial effects, but these were mediated via changes in mineral homeostasis rather than via direct effects of PTH. Results attributable to PTX were similar to those previously obtained by dietary restriction of phosphate intake.

Does modifying dietary lipids influence the progression of renal failure?

Recent studies have identified important effects of dietary fatty acid composition in animals with chronic renal disease, particularly in dogs. The theoretic basis for these effects provides a rationale for the use of diets enriched with omega-3 (but not omega-6) polyunsaturated fatty acids. A therapeutic trial with a diet enriched with omega-3 polyunsaturated fatty acids should be considered as a maneuver designed to slow the rate of progression of chronic renal disease in dogs.

A retrospective study of multicentric bovine renal cell tumors.

Tissues from twenty mature cows with primary renal cell tumors were submitted over an 11-year period because of gross lesions detected during routine slaughter and inspection. Tumors visualized grossly were multiple and bilateral in seven cattle, multiple within one kidney in four cattle, and solitary in nine cattle. The tumors were primarily cortical, yellow-orange to tan, proliferative, well circumscribed, and extended above the capsular surface of the kidney. Tumors were microscopically multiple even when grossly described as solitary lesions, except in one cow. Twelve tumors (60%) were microscopically multiple in one kidney, seven tumors (35%) were multiple and bilateral, and only one cow (5%) exhibited extrarenal metastasis. Tumors from nineteen cows were composed of eosinophilic granular epithelial cells; tumors from one cow were clear cell type. Each tumor contained several histologic patterns. Corpora amylacea, proteinaceous secretions, and hemosiderin were characteristic findings in bovine renal cell carcinoma. All 20 cows with renal cell tumors exhibited positive immunoreactivity to uromodulin (Tamm-Horsfall protein).

Effects of aging and dietary protein intake on uninephrectomized geriatric dogs.

Thirty-one clinically normal Cocker Spaniels, Miniature Schnauzers, and Doberman Pinschers (28 female, 3 male) 7 to 8 years old were uninephrectomized (month -2) to increase the risk of renal damage associated with reduction of renal mass. Two diets, differing principally in protein concentration, were used to test the hypothesis that high dietary protein intake causes renal damage in aging dogs. For 2 months after uninephrectomy, all dogs were fed diet A (18% protein). After glomerular filtration rate (GFR) was measured (month 0), 16 dogs were assigned to group A and were fed diet A for an additional 48 months. The other 15 dogs were assigned to group B, and were fed diet B (34% protein) for the subsequent 48 months. At 6-month intervals, GFR and urine protein-to-creatinine ratio (UP/C) were determined. At 48 months, terminal studies were done, survivors were euthanatized, and tissues were examined. Of 16 dogs in group A, 10 survived, compared with 13 of 15 in group B. Among survivors, a significant difference in GFR was not found between groups A and B, and decrease in GFR was not evident with time in either group. At 48 months, oral administration of casein caused minor acute effects on GFR and renal plasma flow in dogs of groups A and B. The UP/C values increased significantly (P = 0.001) from baseline values, but the increase was not progressive. The UP/C values were not affected by diet. Some dogs in both groups developed UP/C > 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural examination and cell count determinations of avian glomeruli from grossly normal and grossly swollen kidneys of broilers at slaughter.

Kidneys from broiler chickens at slaughter (6 to 7 weeks of age and mixed sex) were collected by U.S. Department of Agriculture personnel. Forty kidneys were collected from grossly normal birds with grossly normal kidneys (Group D). Grossly swollen kidneys were collected from birds that were otherwise grossly normal (Group A), that had gross lesions of Marek's disease (Group B), or that had gross lesions of squamous cell carcinoma (Group C). These kidneys were fixed in Carson's 10% buffered formalin, embedded in plastic, sectioned at 2 microns, and then stained with periodic acid-Schiff-hematoxylin for glomerular cell counting. Tissue was also processed for electron microscopy from six Group D birds and from six birds total from Groups A, B, and C that had the most severe histologic glomerular lesions. Glomerular tuft cell counts and visceral epithelial cell counts were performed by light microscopy at a magnification of 100x (oil immersion). Total tuft cell counts of all abnormal groups (A, B, and C) were significantly higher (P < 0.05) than those of Group D. Reptilian glomerular tuft cell counts for all abnormal groups were significantly higher (P < 0.05) than the reptilian glomerular tuft counts for Group D. Mammalian glomerular tuft cell counts for Groups A and B were significantly higher than those of the control group (Group D). Electron microscopic examination of the glomeruli from selected birds revealed no dense deposits in the basement membrane and no effacement of epithelial podocyte foot processes. No essential ultrastructural differences were noted between the control group and the abnormal groups.

Effects of parathyroid hormone depletion in dogs with induced renal failure.

Six parathyroidectomized (PTX) and 6 control dogs had renal mass reduced by 15/16, and were studied for effects of parathyroid hormone depletion on progression of renal failure. All PTX dogs and 4 of 6 control dogs survived until necropsy after 32 weeks. Plasma parathyroid hormone concentration was undetectable in PTX dogs throughout the study, but was greater than normal in control dogs. Serum inorganic phosphate (P) concentration was increased in PTX dogs (6.8 +/- 0.1 mg/dl) and in control dogs (7.5 +/- 0.2), but did not differ significantly (P = 0.254) between groups. Ionized blood calcium values (Ca2+) were significantly (P = 0.014) lower in PTX dogs (1.31 +/- 0.01 mmol/L) than in control dogs (1.36 +/- 0.00 mmol/L), but were more variable in PTX dogs. Values in PTX dogs were not significantly different from those in control dogs for glomerular filtration rate (P = 0.914), plasma creatinine concentration (P = 0.903), and urine protein to creatinine ratio (P = 0.756) determined at intervals during the study. Terminal glucose tolerance and plasma insulin concentrations, P tolerance, and renal P excretion did not differ between groups. Histologic comparison of kidneys removed during reduction of renal mass with kidneys removed at necropsy revealed development of lesions in both groups of dogs, and no protective effect from parathyroidectomy. Mineral analysis of aorta, brain, heart, lungs, and skeletal muscle obtained at necropsy revealed no significant difference between PTX and control groups. Renal cortical calcium concentration was significantly (P < 0.05) greater in kidneys obtained at necropsy then in kidneys obtained during nephrectomy, but PTX did not protect renal cortex from calcium deposition.

Intracapsular subtotal prostatectomy in normal dogs: use of an ultrasonic surgical aspirator.

In an attempt to reduce postoperative incontinence associated with excisional prostatectomy and the recurrence of prostatic disease after less radical surgeries, a new technique for subtotal prostatectomy was developed using an ultrasonic surgical aspirator. During laparotomy, a longitudinal incision was made in the ventral surface of each lobe of the prostate gland. Biopsies for histology and culture were taken. Through the ventral incisions, the ultrasonic surgical aspirator was used to resect approximately 85% of the glandular tissue from inside the capsule. The ultrasonic surgical aspirator allowed resection of the glandular tissue without damaging the vessels, nerves, and connective tissue stroma. The ventral portion of the capsule was excised. The dorsal portions of the capsule were apposed on the ventral midline by suturing their ventral margins to form a periurethral cuff. As preclinical research, seven intact male dogs were evaluated by physical examination, complete blood cell count, serum urea nitrogen, urinalyses, and urethral pressure profile (UPP) with urethral electromyograms (EMGs). The dogs underwent subtotal prostatectomy and castration. All dogs were continent after surgery. UPPs and EMGs at 1 and 2 months after surgery were no different than before surgery. This contrasts to our previous studies in which excisional prostatectomy reduced maximal urethral closure pressure (MUCP) in dogs without prostatic disease. The use of the ultrasonic surgical aspirator for intracapsular subtotal prostatectomy facilitated removal of glandular tissue with decreased hemorrhage and provided preservation of the prostatic urethra, nerves, and vessels involved in maintaining urinary continence.

Selective parathyroidectomy of the dog.

Selective parathyroidectomy (PTX) is preferred to thyroparathyroidectomy (TPTX) when specific effects of parathyroid hormone depletion are being studied. However, because of the anatomic proximity of thyroid and parathyroid glands, TPTX often is performed, leaving animals depleted of thyroxine (T4) and calcitonin as well as parathyroid hormone (PTH). In the present study, six normal dogs had parathyroid tissue and about seven-eighths of thyroid tissue removed. This quantity of thyroid tissue was inadequate to maintain normal serum T4 concentrations, despite allowance of 168 days for thyroid recovery. Five of six dogs with reduced renal mass had successful selective PTX and normal serum T4 concentrations at 28 days, when one-half or more of thyroid tissue was spared. We conclude that with attention to the surgical technique, selective PTX can be achieved in a high percentage of dogs and sufficient thyroid tissue spared to maintain euthyroidism.

Histologic and morphometric examination of avian glomeruli from normal and swollen kidneys of broilers at slaughter.

Normal and abnormal kidneys collected from broiler chickens at slaughter (6 to 7 weeks of age and of mixed sex) were evaluated to establish histopathologic and morphometric parameters for broilers. Normal kidneys (group D) had an overall mean glomerular diameter of 67.4 +/- 27.8 microns. Abnormal groups (Groups A, B, and C) had an average glomerular diameter of 75.2 +/- 32.1 microns, which was significantly different (P < 0.01) from that of Group D. All glomerular diameters in Group A (otherwise normal birds with swollen kidneys) were significantly different (P < 0.01) from corresponding diameters in Group D. In Group B (birds condemned for Marek's disease virus), only the mammalian glomeruli were significantly different from Group D mammalian glomeruli (P < 0.01). A significant increase in glomerular density was observed for all abnormal groups and glomerular types. The data indicate that glomerular diameter and cellularity might be practical and sensitive indicators of early glomerular changes that can occur in grossly swollen kidneys. Increased glomerular density indicates tubular loss or increase in glomerular numbers.

Early renal disease in BHE/cdb rats is less in rats fed beef tallow than in rats fed menhaden oil.

The effects of feeding a 1% corn oil-9% menhaden oil or beef tallow diet on the early phase of diabetic nephropathy in BHE/cdb rats was studied. The diet groups were subdivided into rats with or without impaired glucose tolerance. Those fed menhaden oil had renal hypertrophy, mild albuminuria, decreased creatinine clearance, increased urea clearance, and more severe lesion scores than rats fed beef tallow. No differences in glomerular filtration rate, Na+, K+-ATPase activity, sorbitol dehydrogenase, or inositol 1, 4, 5-phosphate were observed. Beef tallow-fed rats had higher serum triglyceride levels and renal cholesterol levels. Renal and hepatic fatty acid profiles reflected the fatty acid profile of the dietary fat. These results suggest that beef tallow conferred a protective effect on the renal tissues of these diabetes-prone rats.

Effects of dietary phosphorus and protein in dogs with chronic renal failure.

Four diets were formulated to contain: 16% protein and 0.4% phosphorus--diet 1; 16% protein and 1.4% phosphorus--diet 2; 32% protein and 0.4% phosphorus--diet 3; and 32% protein and 1.4% phosphorus--diet 4. Forty-eight dogs were fed diet 1 for 3 months after surgical reduction of renal mass, then were allotted to 4 groups of 12 dogs each, with equal mean values for glomerular filtration rate (GFR). Dog of groups 1-4 were fed diets 1-4, respectively, for 24 months. Data collected from the dogs during and at termination of the study were analyzed statistically for effects of dietary protein, phosphorus (P), time, and interactions between these factors. During the 24 months of study, 24 dogs developed uremia and were euthanatized for necropsy. Necropsy also was performed on the remaining 24 dogs after they were euthanatized at the end of the study. Dog survival was significantly enhanced by 0.4% P diets (vs 1.4% P diets), but survival was not significantly influenced by amount of dietary protein. The 0.4% P diets (vs 1.4% P diets) significantly increased the period that GFR remained stable before it decreased, but dietary protein did not have significant effect. Significant blood biochemical changes attributed to P, protein, and time were identified during the study. Terminally, plasma parathyroid hormone concentration was significantly increased from prediet values in all groups of dogs. Urine protein excretion was not significantly affected by dietary amount of either protein or P, when measured by either timed urine collection or urine protein-to-creatinine ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Invasion of enterocytes in cultured porcine small intestinal mucosal explants by Salmonella choleraesuis.

Porcine small intestinal explants maintained in vitro were inoculated with Salmonella choleraesuis to study the characteristics of its invasion of enterocytes. The explants were fixed at selected intervals for up to 12 hours after inoculation and examined by conventional light microscopy, immunoperoxidase staining, and transmission electron microscopy. Although there was diffuse loss of villous enterocytes during the first hour of incubation, the villi were reepithelialized by the end of 2 hours of culture, and the mucosal epithelium remained intact and appeared to be viable through 12 hours of culture. Intraepithelial S choleraesuis were not detected before 6 hours after inoculation, but after 12 hours of incubation, bacteria were numerous within enterocytes. Ultrastructurally, penetration of the brush border by S choleraesuis resulted in focal loss of microvilli. Bacteria were endocytosed into membrane-bound vacuoles where most remained, but a few were free within the cytoplasm of enterocytes. Invasion of the explants closely resembled that described for live animal and cell culture models of Salmonella spp invasion.

Cephaloridine nephrotoxicity is potentiated by selenium deficiency but not copper deficiency in rats.

Lipid peroxidation may contribute to the nephrotoxicity of cephaloridine, a beta-lactam antibiotic. Copper and Se may protect against free radical damage, and dietary Se deficiency potentiates cephaloridine nephrotoxicity. The objectives of this study were to further investigate potentiation of cephaloridine toxicity by Se deficiency and to determine whether Cu deficiency increases cephaloridine-induced injury. Weanling male Sprague-Dawley rats were fed adequate, Cu-deficient, Se-deficient, and Se and Cu-deficient diets for 4 wk and subsequently injected i.p. with cephaloridine (1200 mg/kg body wt) or saline. Nephrotoxic response to cephaloridine occurred, with increased plasma urea, kidney weight, excretion of urinary enzymes, and kidney lesions. Cephaloridine also increased plasma sorbitol dehydrogenase activity. Selenium deficiency depressed kidney glutathione peroxidase activity (78%) and potentiated cephaloridine nephrotoxicity. Copper deficiency did not increase cephaloridine nephrotoxicity; the small depression (13%) in kidney Cu,Zn-superoxide dismutase activity may not have been sufficient to impair antioxidant status. However, the marked depression in kidney glutathione peroxidase activity during Se deficiency may have impaired antioxidant status and enhanced cephaloridine-induced injury. In contrast to results in the kidney, neither Se deficiency nor Cu deficiency potentiated cephaloridine hepatotoxicity, as assessed by plasma SDH activity.