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Biomedical subjects

S Bornstein

Publications and source records attributed to S Bornstein.

At least 19 recordsLinked to original sources

The prototypic antidepressant drug, imipramine, but not Hypericum perforatum (St. John's Wort), reduces HPA-axis function in the rat.

Dysregulation in corticotropin-releasing hormone (CRH) secretion in the hypothalamus-pituitary-adrenal (HPA) axis may be involved in the etiology of major depressive disorder (MDD). Chronic therapy with standard antidepressant drugs, such as imipramine, can downregulate HPA axis function, indicating that the HPA axis may be an important target for antidepressant action. We tested several doses of a standardized commercial preparation of Hypericum perforatum plant extract (popularly known as St. John's Wort), a medicinal herb used for treating mild depressive symptoms, to determine whether it also modulated HPA axis function. Chronic imipramine treatment (daily injections for 8 weeks) of male Sprague-Dawley rats significantly downregulated circulating plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone compared to animals treated with saline. However, chronic St. John's Wort treatment (daily gavage for 8 weeks) had no effect on plasma ACTH or corticosterone, even at the highest doses tested. Our results confirm previous findings that imipramine may have significant peripheral HPA axis-mediated effects. However, our data does not support any role for H. perforatum in modulation of HPA axis function, suggesting that alternative pathways may be involved in mediating its antidepressant effects.

Adrenal Glands↗

Application of the California mastitis test in intramammary Streptococcus agalactiae and Staphylococcus aureus infections of camels (Camelus dromedarius) in Kenya.

A study was conducted on 207 lactating camels in six herds in Kenya to evaluate the California mastitis test (CMT) for the detection of intramammary infections (IMIs) caused by Streptococcus agalactiae and Staphylococcus aureus and to investigate the prevalence of both the pathogens in the camel udder. IMI with S. agalactiae was found in 12% of all camels sampled. IMI with S. aureus was present in 11% of all camels sampled. The herd-level prevalence of IMI varied between 0 and 50% for S. agalactiae and between 0 and 13% for S. aureus. Longitudinal observations over 10-12 months confirmed persistent infections for both pathogens. Observations in one herd suggested that camel pox was a contributing factor in spreading and exacerbating S. agalactiae udder infections.The CMT had quarter-level sensitivities of 77 and 68% for S. agalactiae and S. aureus in camels, respectively. The CMT specificities were 91% for both the pathogens.

Animals↗

The importance of adrenocortical glucocorticoids for adrenomedullary and physiological response to stress: a study in isolated glucocorticoid deficiency.

Glucocorticoids are required for the normal functioning of chromaffin cells and their capacity to produce epinephrine. This was modeled in a unique clinical syndrome of isolated glucocorticoid deficiency due to unresponsiveness to ACTH. The working hypotheses were that in patients with isolated glucocorticoid deficiency, adrenomedullary epinephrine would be suppressed despite replacement therapy; that norepinephrine might show a compensatory response; and that the physiological response to stress would reflect these changes. Toward these hypotheses, patients with ACTH unresponsiveness on glucocorticoid replacement were subjected to three levels of acute stress: assumption of upright posture, cold pressor, and exercise. Their catecholamine and physiological response were monitored. Patients with isolated glucocorticoid deficiency of this study had severe adrenomedullary dysfunction, characterized by a minimal resting production of epinephrine (6 +/- 2 pg/ml compared with 64 +/- 22 pg/ml of the controls) and a minimal response to stress. A slight compensatory increase of norepinephrine was found in response to cold pressor test (754 +/- 200 pg/ml compared with 431 +/- 73 pg/ml of the control). The physiological response is characterized by low systolic blood pressure and high pulse rate in rest and mild stress and in a pressor response to exercise (diastolic 87 +/- 5 mm Hg, compared with 73 +/- 2 mm Hg of the control). It is concluded that intra-adrenal glucocorticoids are essential for epinephrine secretion, that norepinephrine may be compensatory, and that these result in a distinct physiological response. The implications of the pressor response to exercise, the declining pulse pressure, and the increased pulse response insinuate a lower physical fitness in patients with adrenal insufficiency.

Adaptation, Physiological↗

Sero-prevalence of granulocytic Ehrlichia spp. and Borrelia burgdorferi sensu lato in Swedish dogs 1991-94.

In Sweden, 2 tick-borne zoonotic diseases, granulocytic ehrlichiosis and borreliosis, are frequently diagnosed in dogs, using serological assays. The aims of this study were to determine the sero-prevalences of antibodies to Ehrlichia spp. and Borrelia burgdorferi sensu lato during 1991-94 in dogs, not clinically suspected to be infected with either of the 2 agents. Samples (n = 611) were selected from a serum bank using a systematic sampling strategy, stratified across the 4-y period. The stored sera had originally been submitted in order to verify or rule out infection with Sarcoptes scabiei. The overall sero-prevalence for Ehrlichia spp. was 17.7% and for Borrelia burgdorferi sensu lato 3.9% (n = 588). Only a few dogs in the northern part of Sweden were sero-positive for Ehrlichia spp. and none were positive for Borrelia burgdorferi sensu lato. An increased sero-prevalence of Ehrlichia spp. was seen during the years studied. The sero-prevalence of Ehrlichia spp. varied with season. Sero-positivity to both agents increased with age. Both diseases are considered zoonotic, and the increase in sero-prevalence of Ehrlichia spp. over the years may reflect the degree of infection in ticks and may have implications for human health.

Age Factors↗

Eradication of porcine sarcoptic mange within a health declared production model.

The success of a large-scale eradication programme against sarcoptic mange was evaluated in piglet producing herds belonging to the health class LSO 2000. These farms are monitored to be free from sarcoptic mange, swine enzootic pneumoniae, swine dysentery and progressive atrophic rhinitis. The local veterinarians were instructed to eradicate sarcoptic mange from the herds by 2 ivermectin injections 14 days apart or 3 treatments with phoxim pour-on 6 days apart before the farms were able to join the health class. The study consisted of a questionnaire administered to the farmers, farm visits and follow-ups associated with the regular control of the health class. A questionnaire was sent to all of the 379 accepted farrowing farms. Altogether 323 farmers had initiated an eradication programme at least 7 months before the questionnaire was distributed and 96% of them believed that the mange eradication programme had been successful. In most of the successful herds (90%), the local veterinarian had treated the animals by the recommended methods, and the majority of the farmers (88%) had cleaned and sprayed the pens with insecticides on the days of treatment. Three out of the 7 unsuccessful farms had employed methods other than those recommended. Twenty-five herds were randomly selected for an intensified control. The rubbing index was < or = 0.1 in all herds visited, indicating freedom from mange. Sows or gilts, 15-20 animals per farm, were skin scraped and no Sarcoptes scabiei was found. The same animals were blood sampled and serum antibodies to S. scabiei were measured by an indirect ELISA. All except 1 farm had low optical density (OD) values in most of the samples. The owner of that farm had become uncertain about the mange status of the herd and had recently retreated all animals with acaricides. The number of complaints about mange in the finishing units buying health class feeder pigs was low. The study demonstrates that it is possible to run an eradication programme against sarcoptic mange, in which a large number of farmers together with their veterinarians participate. It is possible to eradicate mange not only at the herd but also at the population level. The ELISA test employed proved to be a possible tool to monitor the efficacy of mange-eradication programmes.

Administration, Topical↗

Elimination of Sarcoptes scabiei in pig herds by single or double administrations of an avermectin.

Attempts to eliminate Sarcoptes scabiei var. suis were made in 2 piglet producing herds by intramuscular injections with doramectin (Dectomax, Pfizer inc., New York, USA). No hygienic measures of the environments were undertaken. In herd A, all animals were treated twice at a 14-day interval. Theoretically it should be possible to eliminate the mite with a single injection and therefore the animals in herd B were treated only once. The results were measured by attempts to demonstrate S. scabiei by skin scrapings, by recording skin lesions, by establishing rubbing indexes, and by measuring serum antibodies to S. scabiei. All adult animals greater than 8 months of age and 15 weaned piglets 8-16 weeks of age per herd were investigated prior to treatments and every fourth month for a total of 20 months following administration of the treatments. Live S. scabiei were demonstrated prior to treatments in both herds, but no further. Skin lesion scores, rubbing indexes and serum antibody levels remained low throughout the study. It is possible to eliminate S. scabiei from a herd with one single injection of doramectin. Precautions must be taken to ensure that all animals get a correct dose and that the drug is properly administered.

Animals↗

The efficacy of simplified eradication strategies against sarcoptic mange mite infections in swine herds monitored by an ELISA.

Eradication programmes directed against Sarcoptes scabiei var. suis, performed without any disinfection of the environment, were compared to an eradication programme including a simultaneous environmental disinfection. The performance of such programmes would be facilitated considerably if environmental disinfection could be avoided. The trial was conducted in four conventional piglet-producing herds designated A-D. All herds suffered from a subclinical but persistent infection with the sarcoptic mite. Herd A was treated with two injections of ivermectin and simultaneously disinfection of the environment was done. In the other herds, the animals were treated twice (B and C) or three times (D) with acaricides (ivermectin or phoxim) at intervals of 7-12 days without any simultaneous disinfection of the buildings or environment. The results were monitored by attempts to demonstrate the mite by skin scrapings, and by monitoring the levels of serum antibodies to Sarcoptes scabiei by an ELISA. Samples were taken from all adults and from 20% of the piglets aged 10-12 weeks, before initiating the control programmes, every third month during the first year and a final sampling 18 months after the treatments. After treatment, the levels of antibodies continuously decreased. Presumably dead S. scabiei were demonstrated in one sow from two of the herds 3 months after initiating acaricidal treatments. S. scabiei was not demonstrated later, nor from skin scrapings of the piglets. The results obtained demonstrate that it is possible to eradicate sarcoptic mange mites in swine herds with the use of simplified eradication programmes. The success of such programmes may efficiently be monitored by measuring the levels of serum antibodies to S. scabiei.

Animals↗

Chronic administration of the non-peptide CRH type 1 receptor antagonist antalarmin does not blunt hypothalamic-pituitary-adrenal axis responses to acute immobilization stress.

Antalarmin is a pyrrolopyrimidine compound that antagonizes corticotropin-releasing hormone (CRH) type 1 receptors (CRHR1). In order to assess the effects of antalarmin treatment on hypothalamic-pituitary-adrenal (HPA) function we measured the plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone in animals treated with either antalarmin or vehicle for 1 week or for 8 weeks. We found that antalarmin treatment for 1 week did not affect basal concentrations of ACTH or corticosterone. In contrast, treatment for 8 weeks significantly lowered basal ACTH and corticosterone concentrations and also significantly decreased the basal corticosterone to ACTH ratio, indicating decreased basal adrenocortical responsiveness to ACTH. However, immobilization stress resulted in ACTH and corticosterone concentrations that were the same in animals treated with vehicle or antalarmin for either 1 or 8 weeks. We conclude that even though 8-week antagonism of CRHR1 by the non-peptide antalarmin blunts basal concentrations of ACTH and corticosterone, and affects the adrenal responsiveness to ACTH, it does not blunt the HPA response to acute stress, and it does not appear to cause stress-induced adrenal insufficiency.

Adrenocorticotropic Hormone↗

Restoration of adrenal steroidogenesis by adenovirus-mediated transfer of human cytochromeP450 21-hydroxylase into the adrenal gland of21-hydroxylase-deficient mice.

21-Hydroxylase deficiency, a potentially fatal disease due to deletions or mutations of the cytochrome P450 21-hydroxylase gene (CYP21), causes congenital adrenal hyperplasia (CAH) with low or absent glucocorticoid and mineralocorticoid production. The feasibility of gene therapy for CAH was studied using 21OH-deficient mice (21OH-) and a replication-deficient adenovirus containing the genomic sequence of human CYP21 (hAdCYP21). Intra-adrenal injection of hAdCYP21 in 21OH- mice induced hCYP21 mRNA with the highest expression from 2 to 7 days before a gradual decline. 21OH activity measured in adrenal tissue increased from undetectable to levels found in wild-type mice 2 to 7 days after AdhCYP21 injection. Adrenal morphology of 21OH- mice showed lack of zonation, and hypertrophy and hyperplasia of adrenocortical mitochondria with few tubulovesicular christae. These morphological abnormalities were markedly improved 7 days after hAdCYP21 gene therapy. Plasma corticosterone increased from undetectable levels to values similar in wild-type mice by 7 and 14 days, declining over the next 40 days. This is the first demonstration that a single intra-adrenal injection of an adenoviral vector encoding CYP21 can compensate for the biochemical, endocrine and histological alterations in 21OH-deficient mice, and shows that gene therapy could be a feasible option for treatment of CAH.

Adenoviridae↗

Knocking out the stress response.

Transgenic animals and knockout mice have been generated with defined defects in various components of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. These models provide valuable and novel insights into the development, crosstalk, organization, and functioning of the stress system.

Animals↗

Typical hormonal profiles are accompanied by increased immunoreactivity of theca folliculi steroid 17 alpha-hydroxylase P450 in polycystic ovary syndrome.

The localisation and expression of steroid 17 alpha-hydroxylase had been studied in ovaries obtained from 40 patients in whom polycystic ovary syndrome (PCO) was diagnosed, and in 15 normal ovaries. In patients, elevated serum LH and testosterone and normal FSH, prolactin and dehydroepiandrosterone levels were recorded. Serum oestradiol concentration was slightly decreased. Immunohistochemical staining with the use of antibody directed against human cytochrome P450c17 (CYP17) revealed that in polycystic as well as in normal ovaries, steroid 17 alpha-hydroxylase is localised mainly in the thecal cells of atretic follicles and in the interstitial cells of the stroma. Greater intensity of the immunohistochemical reaction in the polycystic ovaries than in normal controls, indicates a higher concentration of CYP17 and suggests increased expression of steroid 17 alpha-hydroxylase. It is postulated that the increased expression of ovarian steroid 17 alpha-hydroxylase is an important contributory factor in the pathogenesis of PCO.

Adult↗

Apoptosis in the adrenal gland of non-obese diabetic (NOD) mice.

Apoptosis appears to play an important role in the development of diabetes in the non-obese diabetic (NOD) mouse. Since the autoimmune process leading to the manifestation of insulin dependent diabetes mellitus (IDDM) can also affect the sympathochromaffin system, we analyzed the role of apoptosis and infiltration of the adrenal medulla as features of this autoimmune process in parallel with the development of diabetes. Prediabetic and diabetic NOD mice aged 3 to 30 weeks were studied and compared with control mice. Apoptosis was assessed by in situ end-labeling method and ultrastructural analysis. Adrenals were screened for lymphocytic infiltration by conventional hematoxylin-eosin staining. Chromaffin cells were characterized by immunohistochemical staining against synaptophysin and tyrosine hydroxylase. Apoptotic nuclei were detected in all mice studied at a very low level, mainly occuring within the connective tissue between medulla and cortex. The maximum score was achieved at 3 weeks (1.91+/-0.48 apoptotic cells/1000 counted cells; n = 4). There was no significant difference between NOD mice and control mice. No correlation could be found between blood glucose levels and apoptosis. On the ultrastructural level, apoptotic cells presented typical features of apoptosis, i.e. condensed nuclei and cytoplasm. Neither in NOD mice nor in controls lymphocytic infiltration or fibrosis of the adrenal was detected. Even NOD mice with overt diabetes did not exhibit morphological signs of medullitis. In summary, no signs of immune destruction of the adrenal medulla in NOD mice aged 3 to 30 weeks could be detected.

Adrenal Cortex↗

The spread of porcine sarcoptic mange during the fattening period revealed by development of antibodies to Sarcoptes scabiei.

Using an indirect ELISA based on a whole body homogenate of Sarcoptes scabiei var vulpes, the development of serum antibodies to S. scabiei var suis during the fattening period was studied in two herds, purchasing fatteners and performing age segregated production systems. All the pigs in one of the herds were treated with ivermectin on the same day within a week after arrival, while no precautions were made to prevent sarcoptic mange in the other herd. In both herds, a transient immune response to S. scabiei was detected in some animals during the early fattening period, reflecting that these pigs had been exposed to S. scabiei before delivery to the fattening units. It also indicated that they had been treated with acaricides close to allocation. The incidence of animals seropositive to S. scabiei was initially low in both herds. The infection spread gradually as indicated by increasing optical densities of antibodies to S. scabiei, especially during the second half of the rearing period. This increase was more pronounced in the herd which had received no prophylactic treatment to sarcoptic mange. The infection with S. scabiei was found to have spread to more animals towards the end of the fattening period in that herd. It was concluded that a single injection with the acaricide on arrival at the fattening farm decreased and delayed the spread of the infection, but did not eradicate the mite infection. The results showed that conventional pigs sold as fatteners at present may be infected with S. scabiei and that precautions aimed at preventing sarcoptic mange therefore, are indicated in fattening herds. In this context, the ELISA employed could be a valuable means of discriminating between S. scabiei var suis infected piglet producing herds and uninfected herds.

Animals↗

Serodiagnosis of sarcoptic mange in pigs.

A serodiagnostic test (ELISA) for detecting antibodies to Sarcoptes scabiei in the sera of pigs was evaluated. The ELISA results from 221 specific pathogen-free pigs of three different age categories were used to establish a cut-off value for the assay. Background optical density values differed significantly between the three groups, the sows having the highest values. The mean + 3 sd of their values was chosen as the cut-off. Four farrow-to-finish herds of pigs with sarcoptic mange were investigated. Skin scrapings were taken from each animal for the demonstration of S scabiei and their sera were assayed for the presence of antibodies to the mite. All the herds had active infections with S scabiei and antibodies to S scabiei were found in a significant number of the animals sampled. The sensitivity and specificity of the ELISA were 87.8 and 99.5 per cent, respectively, employing clinical diagnosis as the gold standard. A higher sensitivity (100 per cent), but a lower specificity (32.8 per cent) was obtained when the results of skin scrapings were used as the gold standard.

Animals↗

Evaluation of an enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of sarcoptic mange in swine.

An enzyme-linked immunosorbent assay (ELISA) using an extract from Sarcoptes scabiei var. culpes as antigen was evaluated for its usefulness in monitoring antibodies to S. scabiei var. suis in naturally infected pigs. Five hundred and fifty-eight serum samples from certified Sarcoptes-free pigs (120 from weaned piglets, 218 from fatteners and 220 from adult sows) and 94 samples from certified Sarcoptes-infected pigs (35 from weaned piglets, 45 from fatteners and 14 from adult sows) were examined. The cut-off optical density (OD) values, considered to reflect the presence of antibodies to S. scabiei var. suis, were determined to be 0.059, 0.213 and 0.374 for weaners, fatteners and sows, respectively. The specificity of the ELISA was high (> or = 98%) for all age groups. Sensitivity was highest in the piglets (80%), followed by fatteners (78%) and sows (50%). These results indicate that an ELISA may be a simple and valuable alternative to monitor S. seabiei var. suis infections in naturally infected weaners and fatteners.

Animals↗

Respiratory burst activity of phagocytic cells isolated from the mammary glands and blood of camels (Camelus bactrianus).

The oxidative burst activity of phagocytic cells isolated from camel blood and mammary glands was studied using a chemiluminescence (Cl) assay. The polymorphonuclear leucocytes (PMNL) isolated from camel blood mounted a luminol-dependent Cl response upon stimulation with opsonized zymosan or opsonized Staphylococcus aureus. These responses showed an overall similarity to those described in other mammalian species. The leucocytes isolated from the mammary glands mounted Cl responses similar to those observed with blood PMNL but to a lower magnitude. Like the Cl responses of blood cells, the Cl responses induced by mammary gland leucocytes were associated with degranulation and the release of lysosomal enzymes such as myeloperoxidase (MPO).

Acridines↗