Formation of the early canine CL and the role of prostaglandin E2 (PGE2) in regulation of its function: an in vivo approach.

The mechanisms governing corpus luteum (CL) function in domestic dogs remain not fully elucidated. The upregulated expression of cyclooxygenase 2 and prostaglandin (PG) E2 synthase (PGES) at the beginning of the canine luteal phase indicated their luteotrophic roles, and the steroidogenic activity of PGE2 in the early canine CL has been confirmed in vitro. Recently, by applying a cyclooxygenase 2 (COX2)-specific inhibitor (firocoxib [Previcox]; Merial) from the day of ovulation until the midluteal phase, the luteotrophic effects of PGs have been shown in vivo. This is a follow-up study investigating the underlying endocrine mechanisms associated with the firocoxib-mediated effects on the canine CL. Experimental groups were formed with ovariohysterectomies performed on Days 5, 10, 20, or 30 of firocoxib treatments (10 mg/kg bw/24h; TGs = treated groups). Untreated dogs served as controls. A decrease of steroidogenic acute regulatory (STAR) protein expression was observed in TGs. The expression of PGE2 synthase was significantly suppressed in TGs 5 and 10, and both PGE2 and PGF2α levels were decreased in luteal homogenates, particularly from CL in TG 5. Similarly, expression of the prolactin receptor (PRLR) was diminished in TGs 5 and 20. The expression of PGE2 receptors PTGER2 (EP2) and PTGER4 (EP4), the PG- transporter (PGT), and 15-hydroxy PG dehydrogenase (HPGD) was not affected in TGs. Our results substantiate a direct luteotrophic role of PGs in the early canine CL, i.e., by upregulating the steroidogenic machinery. Additionally, the possibility of an indirect effect on PRL function arises from the increased prolactin receptor expression in response to PGE2 treatment in canine lutein cells observed in vitro.

Niveles de vitamina D en adultos mayores saludables chilenos y su relación con desempeño functional / Vitamin D levels in older healthy Chilean adults and their association with functional performance

Background: People over 60 years old are at risk of Vitamin D deficiency, which can affect functional performance, since this vitamin is involved in muscle function and protein synthesis. Aim: To measure 25OH vitamin D levels in healthy older people from Santiago de Chile, and evaluate their relationship with functional performance. Subjects and Methods: Healthy subjects aged 60 years or more and living in the community were invited to participate. People with chronic diseases, cognitive impairment, physical disability, smokers and those consuming more than three medications per day were excluded. Hand grip and gait speed were measured and a blood sample was obtained to measure 25OH vitamin D by radioimmunoanalysis. Results: One hundred and four participants aged 60 to 98 years (55% females) were studied. Mean vitamin D levels were 17.3 ± 6.1 ng/mL. Females had lower levels than males (15.6 ± 5.8 and 19.2 ± 6.0 ng/mL respectively p < 0.01). Eighty three percent of females and 55.3% of males had values below 20 ng/mL (the cutoff point for deficiency). Only 3.5% of females and 8.5% of males had values of 30 ng/ml or higher. There was a significant correlation between vitamin D levels, gait speed and grip strength (r = 0.32 and 0.34 respectively, p < 0.01), especially in women over 74 years. Conclusions: Vitamin D deficiency is almost universal in healthy adults over 60 years living in Santiago de Chile, especially in women. This deficiency is associated with a deranged functional performance and is a potentially modifiable risk factor for disability.

[Vitamin D levels in older healthy Chilean adults and their association with functional performance]. / Niveles de vitamina D en adultos mayores saludables chilenos y su relación con desempeño functional.

BACKGROUND: People over 60 years old are at risk of Vitamin D deficiency, which can affect functional performance, since this vitamin is involved in muscle function and protein synthesis. AIM: To measure 25OH vitamin D levels in healthy older people from Santiago de Chile, and evaluate their relationship with functional performance. SUBJECTS AND METHODS: Healthy subjects aged 60 years or more and living in the community were invited to participate. People with chronic diseases, cognitive impairment, physical disability, smokers and those consuming more than three medications per day were excluded. Hand grip and gait speed were measured and a blood sample was obtained to measure 25OH vitamin D by radioimmunoanalysis. RESULTS: One hundred and four participants aged 60 to 98 years (55% females) were studied. Mean vitamin D levels were 17.3 ± 6.1 ng/mL. Females had lower levels than males (15.6 ± 5.8 and 19.2 ± 6.0 ng/mL respectively p < 0.01). Eighty three percent of females and 55.3% of males had values below 20 ng/mL (the cutoff point for deficiency). Only 3.5% of females and 8.5% of males had values of 30 ng/ml or higher. There was a significant correlation between vitamin D levels, gait speed and grip strength (r = 0.32 and 0.34 respectively, p < 0.01), especially in women over 74 years. CONCLUSIONS: Vitamin D deficiency is almost universal in healthy adults over 60 years living in Santiago de Chile, especially in women. This deficiency is associated with a deranged functional performance and is a potentially modifiable risk factor for disability.

Compact pnCCD-based X-ray camera with high spatial and energy resolution: a color X-ray camera.

For many applications there is a requirement for nondestructive analytical investigation of the elemental distribution in a sample. With the improvement of X-ray optics and spectroscopic X-ray imagers, full field X-ray fluorescence (FF-XRF) methods are feasible. A new device for high-resolution X-ray imaging, an energy and spatial resolving X-ray camera, is presented. The basic idea behind this so-called "color X-ray camera" (CXC) is to combine an energy dispersive array detector for X-rays, in this case a pnCCD, with polycapillary optics. Imaging is achieved using multiframe recording of the energy and the point of impact of single photons. The camera was tested using a laboratory 30 µm microfocus X-ray tube and synchrotron radiation from BESSY II at the BAMline facility. These experiments demonstrate the suitability of the camera for X-ray fluorescence analytics. The camera simultaneously records 69,696 spectra with an energy resolution of 152 eV for manganese K(α) with a spatial resolution of 50 µm over an imaging area of 12.7 × 12.7 mm(2). It is sensitive to photons in the energy region between 3 and 40 keV, limited by a 50 µm beryllium window, and the sensitive thickness of 450 µm of the chip. Online preview of the sample is possible as the software updates the sums of the counts for certain energy channel ranges during the measurement and displays 2-D false-color maps as well as spectra of selected regions. The complete data cube of 264 × 264 spectra is saved for further qualitative and quantitative processing.

A change of expression in the conserved signaling gene MKK7 is associated with a selective sweep in the western house mouse Mus musculus domesticus.

Changes in gene expression are known to occur between closely related species, but it is not yet clear how many of these are due to random fixation of allelic variants or due to adaptive events. In a microarray survey between subspecies of the Mus musculus complex, we identified the mitogen-activated protein-kinase-kinase MKK7 as a candidate for change in gene expression. Quantitative PCR experiments with multiple individuals from each subspecies confirmed a specific and significant up-regulation in the testis of M. m. domesticus. Northern blot analysis shows that this is due to a new transcript that is not found in other tissues, nor in M. m. musculus. A cis-trans test via allele specific expression analysis of the MKK7 gene in F1 hybrids between domesticus and musculus shows that the expression change is mainly caused by a mutation located in cis. Nucleotide diversity was found to be significantly reduced in a window of at least 20 kb around the MKK7 locus in domesticus, indicative of a selective sweep. Because the MKK7 gene is involved in modulating a kinase signalling cascade in a stress response pathway, it seems a plausible target for adaptive differences between subspecies, although the functional role of the new testis-specific transcripts will need to be further studied.

Liver histopathology and liver and serum alanine aminotransferase and alkaline phosphatase activities in epileptic dogs receiving phenobarbital.

Phenobarbital (PB) therapy is frequently associated with elevated serum alanine aminotransferase (ALT) and alkaline phosphatase (AP) activities in dogs without clinical signs of liver disease. The goal of this study was to determine if increased serum ALT and AP activities in clinically healthy PB-treated epileptic dogs are due to hepatic enzyme induction or to subclinical liver injury. Liver biopsies were obtained from 12 PB-treated dogs without clinical signs of liver disease but with elevated serum ALT and/or AP activities or both. Liver biopsies were obtained from eight healthy control dogs not receiving PB. Biopsies were evaluated histopathologically (all dogs) and liver homogenates were assayed for ALT (all dogs) and AP (six treated dogs, all controls) activities. As a positive control, liver cytochrome P4502B, an enzyme known to be induced by PB, was measured by benzyloxyresorufin-O-dealkylase activity and immunoblotting (five treated dogs, all controls). Serum AP isoenzyme analyses were performed. Results showed that ALT and AP activities in liver homogenates were not increased in treated dogs compared with controls, whereas the positive control for induction, CYP2B, was dramatically increased in treated dogs. Histopathological examination of liver biopsies revealed more severe and frequent abnormalities in treated dogs compared to controls, but similar types of abnormalities were found in both groups. Serum AP isoenzyme analyses in treated dogs demonstrated increased corticosteroid-induced and liver isoenzyme activities compared to controls. Results do not support induction of ALT or AP in the liver as the cause of elevated serum activities of these enzymes due to PB.

Changes in serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs receiving phenobarbital for one year.

A multicentric prospective study was conducted to monitor the effect of phenobarbital on serum total thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations in epileptic dogs. Serum T4 concentrations were determined for 22 epileptic dogs prior to initiation of phenobarbital therapy (time 0), and 3 weeks, 6 months, and 12 months after the start of phenobarbital. Median T4 concentration was significantly lower at 3 weeks and 6 months compared to time 0. Thirty-two percent of dogs had T4 concentrations below the reference range at 6 and 12 months. Nineteen of the 22 dogs had serum TSH concentrations determined at all sampling times. A significant upward trend in median TSH concentration was found. No associations were found between T4 concentration, dose of phenobarbital, or serum phenobarbital concentration. No signs of overt hypothyroidism were evident in dogs with low T4, with one exception. TSH stimulation tests were performed on six of seven dogs with low T4 concentrations at 12 months, and all but one had normal responses. In conclusion, phenobarbital therapy decreased serum T4 concentration but did not appear to cause clinical signs of hypothyroidism. Serum TSH concentrations and TSH stimulation tests suggest that the hypothalamic-pituitary-thyroid axis is functioning appropriately.

Effects of phenobarbital treatment on serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs.

OBJECTIVE: To determine whether phenobarbital treatment of epileptic dogs alters serum thyroxine (T4) and thyroid-stimulating hormone (TSH) concentrations. DESIGN: Cross-sectional study. ANIMALS: 78 epileptic dogs receiving phenobarbital (group 1) and 48 untreated epileptic dogs (group 2). PROCEDURE: Serum biochemical analyses, including T4 and TSH concentrations, were performed for all dogs. Additional in vitro analyses were performed on serum from healthy dogs to determine whether phenobarbital in serum interferes with T4 assays or alters free T4 (fT4) concentrations. RESULTS: Mean serum T4 concentration was significantly lower, and mean serum TSH concentration significantly higher, in dogs in group 1, compared with those in group 2. Thirty-one (40%) dogs in group 1 had serum T4 concentrations less than the reference range, compared with 4 (8%) dogs in group 2. All dogs in group 2 with low serum T4 concentrations had recently had seizure activity. Five (7%) dogs in group 1, but none of the dogs in group 2, had serum TSH concentrations greater than the reference range. Associations were not detected between serum T4 concentration and TSH concentration, age, phenobarbital dosage, duration of treatment, serum phenobarbital concentration, or degree of seizure control. Signs of overt hypothyroidism were not evident in dogs with low T4 concentrations. Addition of phenobarbital in vitro to serum did not affect determination of T4 concentration and only minimally affected fT4 concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Clinicians should be aware of the potential for phenobarbital treatment to decrease serum T4 and increase TSH concentrations and should use caution when interpreting results of thyroid tests in dogs receiving phenobarbital.

Failure to grow.

Failure to grow in pups and kittens can be the result of many factors. Dietary, metabolic, endocrine, parasitic, neoplastic, and genetic diseases may be responsible for a failure to thrive alone or in concert with other disorders. A complete history, physical examination, complete blood cell count, biochemistry profile, and urinalysis are the initial steps to define the underlying disorder(s). Subsequent tests may be needed based on these initial diagnostic results.

Effects of medetomidine on serum osmolality; urine volume, osmolality and pH; free water clearance; and fractional clearance of sodium, chloride, potassium, and glucose in dogs.

OBJECTIVE: To determine effects of i.v. medetomidine administration on selected clinicopathologic variables in dogs. ANIMALS: 6 healthy adult Beagles. PROCEDURE: Dogs were randomly assigned to each of 3 treatments in a crossover study design. Serum osmolality, urine osmolality, urine pH, and fractional clearances of sodium, chloride, potassium, and glucose were determined before and 20, 40, 60, 120, 180, 240, 300, 360, 420, and 480 minutes after i.v. administration of 0.9% NaCl (saline) solution (control) or medetomidine (10 or 20 micrograms/kg of body weight). The urinary bladder was emptied prior to saline or medetomidine administration, and urine volume was determined at the same posttreatment times as those described previously. Free water clearance was calculated for all posttreatment times. RESULTS: After medetomidine administration, serum osmolality, urine volume, free water clearance, and fractional clearance of potassium and glucose increased; urine osmolality decreased. Initially, urine pH and fractional clearance of chloride decreased, then subsequently increased. Fractional clearance of sodium did not change. CONCLUSIONS AND CLINICAL RELEVANCE: Because i.v. administration of medetomidine to dogs at dosages of 10 and 20 micrograms/kg induces a diuretic effect that lasts up to 4 hours, the drug should be used with discretion in hypovolemic or dehydrated dogs, and its use should be avoided in those with urinary tract obstruction.

Effects of medetomidine on serum insulin and plasma glucose concentrations in clinically normal dogs.

OBJECTIVE: To determine the effects of medetomidine, administered i.v., on serum insulin and plasma glucose concentrations in clinically normal dogs. ANIMALS: 6 healthy adult Beagles. PROCEDURE: Dogs were randomly assigned to each of 3 treatments in a prospective cross-over study design. Serum insulin and plasma glucose concentrations were determined before and 20, 40, 60, 120, 180, 240, 300, 360, 420, and 480 minutes after i.v. administration of 0.9% NaCl solution (control) or medetomidine (10 or 20 micrograms/kg of body weight). RESULTS: Mean serum insulin concentration decreased after medetomidine administration and was significantly (P < or = 0.05) lower than control values 20, 40, 60, and 120 minutes after drug administration. Mean plasma glucose concentration tended to increase after medetomidine administration, but did not differ significantly from control values. CONCLUSIONS: In dogs, i.v. administration of medetomidine at dosages of 10 and 20 micrograms/kg transiently decreases serum insulin concentration, but plasma glucose concentration remains within the normal physiologic range. CLINICAL RELEVANCE: Medetomidine can be given at low, preanesthetic dosages without significantly altering plasma glucose concentration in clinically normal dogs.

Pituitary corticotroph macrotumors. Diagnosis and treatment.

Pituitary corticotroph macrotumors occur in 10% to 50% of dogs with PDH. Clinical signs may be only those of hypercortisolism or may include neurologic signs such as stupor, inappetance, circling, or pacing. Currently, CT and MRI are the only tests that can confirm the presence of a pituitary macrotumor in these patients. Results of endocrine testing are not significantly different from those of dogs with a microtumor. When a macroscopic pituitary tumor is identified in a dog with neurologic signs, or if a larger tumor is found in a dog even in the absence of neurologic signs, radiation therapy is currently the treatment of choice. Unfortunately, success rates with treatment are variable. A better response may be seen if the tumor is smaller and neurologic signs are minimal or absent at the time of treatment.

Use of technetium Tc 99m sestamibi for detection of a parathyroid adenoma in a dog with primary hyperparathyroidism.

Double-phase parathyroid gland scintigraphy, using technetium Tc 99m sestamibi, correctly identified the existence and location of a parathyroid adenoma in a dog with primary hyperparathyroidism. The parathyroid adenoma was removed surgically 2 days after scintigraphy. An area of focal radionuclide uptake persisted in the region corresponding to the left external parathyroid gland in the delayed-phase image. Delayed-phase images from 3 healthy dogs and a dog with hypercalcemia of malignancy caused by lymphoma did not reveal an area of persistent radiotracer uptake. Double-phase parathyroid gland scintigraphy, using 99mTc-sestamibi, is a simple, rapid, noninvasive test, which can be used for detection and localization of parathyroid adenomas in hypercalcemic dogs. It also can help to differentiate these dogs from dogs with hypercalcemia of malignancy.

Probable recurrent femoral artery thrombosis in a dog with intestinal lymphosarcoma.

An 11-year-old mixed-breed dog was examined because of chronic diarrhea, anorexia, and weight loss. Clinicopathologic abnormalities included anemia and hypoalbuminemia, and protein-losing enteropathy was identified. Acute, unilateral, femoral artery thrombosis developed before the cause of the protein-losing enteropathy could be identified. The dog was treated with aspirin, and sensation and function of the affected limb returned over the next 5 days, but thrombosis of the opposite femoral artery then developed. The dog was euthanatized, and at necropsy, intestinal lymphosarcoma was the only disease process found. Although disseminated intravascular coagulation is a well-recognized potential complication of neoplasia in dogs, recurrent localized thrombosis, as in this dog, also can develop.

Nutritional therapy for diabetes mellitus.

Dietary therapy affects diabetes management in the dog and cat directly through control of blood glucose and indirectly through control of obesity and lipid abnormalities. Caloric intake, the feeding schedule, food form, macronutrient composition of the diet, and the presence of any concurrent problems must all be considered when planning the dietary regime. Generally, the healthy diabetic dog or cat should be fed a diet with increased fiber and moderate carbohydrate in a quantity sufficient to attain and maintain optimal body weight; whenever possible, the daily food allotment should be divided into multiple small meals that are fed through the day and evening when the physiologic effects of administered insulin are present. Once established, the dietary regime should be kept constant from day to day. Following these guidelines will help minimize postprandial hyperglycemia and may lead to a decreased exogenous insulin requirement. However, if a concurrent disorder has dietary requirements that conflict with those for the diabetic pet, nutritional management of the other disorder should usually take precedence.

Effects of diet on fecal occult blood testing in healthy dogs.

Six dogs were fed each of nine diets to evaluate the effects of diet on fecal occult blood test results. The diets represented a range of different type (i.e. canned, dry or semi-moist), protein and vegetable constituents, and fiber contents. Each diet was fed twice daily for five consecutive days; fecal samples were collected twice daily on days 4 and 5. An o-tolidine test kit and a guaiac paper test kit for fecal occult blood were used. Two hundred and sixteen fecal samples were analyzed (24 samples/diet). When using the guaiac test the following positive results were obtained from fecal samples from dogs consuming a canned meat- and vegetable-based diet (24/24 samples); a canned meat-based diet (24/24 samples); a dry corn and poultry-based diet (9/24 samples); a dry corn, wheat, and meat meal diet (4/24 samples), a canned poultry-based diet (1/24 sample) and a semi-moist soybean meal-based diet (2/24 samples). A total of 64 samples were positive using the guaiac test. Using the o-tolidine test, no samples were positive. The difference between the number of positive results with each test kit was highly significant (p < 0.001). Results indicate that 1) diet affects the specificity of guaiac test fecal occult blood results in the dog and 2) positive o-tolidine test results were not caused by diets fed in the study.

Effects of dietary fiber supplementation on glycemic control in dogs with alloxan-induced diabetes mellitus.

The effect of a high insoluble-fiber (IF) diet containing 15% cellulose in dry matter, high soluble-fiber (SF) diet containing 15% pectin in dry matter, and low-fiber (LF) diet on glycemic control in 6 dogs with alloxan-induced insulin-dependent diabetes mellitus was evaluated. Each diet contained greater than 50% digestible carbohydrate in dry matter. A crossover study was used with each dog randomly assigned to a predetermined diet sequence. Each dog was fed each diet for 56 days. Caloric intake was adjusted weekly as needed to maintain each dog within 1.5 kg of its body weight measured prior to induction of diabetes mellitus. All dogs were given pork lente insulin and half of their daily caloric intake at 12-hour intervals. Mean (+/- SEM) daily caloric intake was significantly (P less than 0.05) less when dogs consumed the IF diet vs the SF and LF diets (66 +/- 3 kcal/kg, 81 +/- 5 kcal/kg, and 79 +/- 4 kcal/kg, respectively). Serum alkaline phosphatase activity was significantly (P less than 0.05) higher when dogs consumed the LF diet vs the IF and SF diets (182 +/- 37 IU/L, 131 +/- 24 IU/L, and 143 +/- 24 IU/L, respectively). Mean postprandial plasma glucose concentration measured every 2 hours for 24 hours, beginning at the time of the morning insulin injection, was significantly (P less than 0.05) lower at most blood sampling times in dogs fed IF and SF diets, compared with dogs fed the LF diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute renal failure associated with contrast medium administration in a dog.

Intravenous administration of an ionic radiographic contrast medium was believed to have caused acute oliguric renal failure in a young dog. Intravenous pyelography was done on a healthy 14-month-old female Lhasa Apso prior to reconstructive surgery for pseudohermaphroditism. Within 24 hours of the radiographic procedure, acute oliguric renal failure developed. Cause for the renal failure was not found other than the recent IV administration of radiographic contrast medium. Treatment with fluids, furosemide, and dopamine was successful in returning renal function to normal. Various adverse reactions to IV administration of contrast media in human beings and animals have been reported; however, to our knowledge, acute renal dysfunction induced by IV administration of contrast material has not been reported in dogs.

Serum free thyroxine concentration in healthy dogs, dogs with hypothyroidism, and euthyroid dogs with concurrent illness.

Serum free thyroxine (fT4), thyroxine (T4), and 3,5,3'-triiodothyronine (T3) concentrations were determined in 62 healthy dogs, 51 dogs with hypothyroidism, and 59 euthyroid dogs with concurrent dermatopathy or concurrent illness for which hypothyroidism was a diagnostic consideration. Status of thyroid function was based on history, physical findings, results of thyrotropin response testing, requirement for thyroid hormone replacement therapy, and in 31 dogs, on results of histologic examination of a thyroid gland biopsy specimen. Serum fT4 concentration was determined, using a single-stage radioimmunoassay. Mean (+/- SD) serum fT4 concentration was significantly (P less than 0.05) greater in healthy dogs vs dogs with hypothyroidism (0.51 +/- 0.27 ng/dl vs 0.10 +/- 0.07 ng/dl). Significant difference in mean serum fT4 concentration was not evident between dogs with hypothyroidism and euthyroid dogs with hyperadrenocorticism (0.16 +/- 0.13 ng/dl) or peripheral neuropathy (0.19 +/- 0.10 ng/dl). Mean serum fT4 concentration in all other groups of euthyroid dogs with concurrent illness was similar to values in healthy dogs and was significantly (P less than 0.05) greater, compared with values in dogs with hypothyroidism. Similar results were found for mean serum T4 concentration. Comparison of serum fT4 vs T4 concentration revealed: sensitivity, 0.97 vs 0.98; specificity, 0.78 vs 0.73; predictive value for a positive test result, 0.79 vs 0.80; predictive value for a negative test result, 0.97 vs 0.97; and accuracy, 0.78 vs 0.86, respectively. Ten (17%) and 12 (20%) of 59 serum fT4 and T4 concentrations, respectively, were inappropriately low in euthyroid dogs with concurrent illness.(ABSTRACT TRUNCATED AT 250 WORDS)