Blindness in dogs with pituitary dependent hyperadrenocorticism: relationship with glucose, cortisol and triglyceride concentration and with ophthalmic blood flow.

Pituitary dependent hyperadrenocorticism (PDH) shows a high morbidity and blindness is one of its complications. Compression of the optic chiasm (OC) by the hypophysis adenoma is one of the causes. Another cause could be due to vascular and metabolic alterations of the PDH. Out of a total of 70 dogs with confirmed diagnosis of PDH, 12/70 showed blindness. In only 2/12 the OC was compromised. Electroretinography in dogs without the OC being compromised showed altered A and B wave patterns. Ophthalmological Doppler showed an alteration of the blood flow only in blind dogs without OC compression. Cortisol concentrations (Co), triglycerides (Tg) and glycaemia (G) were greater in 10 dogs with non-compressive blindness vs. dogs with conserved vision. Loss of vision correlated with the increase in these variables. Blindness in dogs with PDH would be related to changes in retinal blood flow, associated to higher Co, Tg and G concentrations.

Low dose of insulin detemir controls glycaemia, insulinemia and prevents diabetes mellitus progression in the dog with pituitary-dependent hyperadrenocorticism.

Diabetes is often associated with pituitary-dependent hyperadrenocorticism (PDH). Hypercortisolism causes insulin resistance and affects ß-cell function. The purpose of this study was to test if daily administration of a long-acting insulin analogue during the first month of anti-PDH treatment can prevent progress to diabetes in these animals. Twenty-six PDH dogs were divided into three groups: one group with glycaemia <5.83 mmol/L and two groups with glycaemia >5.83 mmol/L and <9.35 mmol/L, one of which received insulin detemir during 4 months. Dogs with glycaemia <5.83 mmol/L and those with glycaemia >5.83 mmol/L which received insulin did not develop diabetes. In the non-insulin group, 6/7 dogs developed diabetes after the third month. There is a 13-fold higher risk of diabetes in dogs with glycaemia >5.83 mmol/L and no insulin treatment. Administering insulin detemir to dogs with PDH and glycaemia >5.83 mmol/L could prevent progression to diabetes.

Valproic acid alters mitochondrial cholesterol transport in Y1 adrenocortical cells.

Several reports suggest putative interactions between valproic acid (VPA) treatment and the hypothalamus-pituitary-adrenal axis. Given that VPA alters mitochondrial functions, an action of this drug on a mitochondrial process such as steroid synthesis in adrenal cells should be expected. In order to disclose a putative action of VPA on the adrenocortical cell itself we evaluated VPA effects on regulatory steps of the acute stimulation of steroidogenesis in Y1 adrenocortical cells. This study demonstrates that VPA increases progesterone production in non-stimulated cells without inducing the levels of Steroidogenic Acute Regulatory (StAR) protein, which facilitates cholesterol transport. This result suggests that VPA increases mitochondrial cholesterol transport through a StAR-independent mechanism and is further supported by the fact that in isolated mitochondria VPA stimulates exogenous cholesterol metabolization to progesterone. VPA also reduces the cAMP-mediated increase of the StAR protein, mRNA levels, promoter activity and progesterone production. In summary, the present data show that VPA can alter steroid production in adrenal cells by a complex mechanism that mainly involves an action on cholesterol access to the inner mitochondrial membrane. The VPA-mediated increase of basal steroidogenesis could be linked to the increase of basal cortisolemia described in patients under VPA treatment.

Diurnal ACTH and plasma cortisol variations in healthy dogs and in those with pituitary-dependent Cushing's syndrome before and after treatment with retinoic acid.

Daytime variations in ACTH and plasma cortisol were studied in healthy dogs and in dogs with pituitary-dependent hypercortisolism (PDH), before and after treatment with retinoic acid. In control dogs ACTH showed a higher concentration at 8.00 AM and between 2.00 and 6.00 PM, with the lowest concentration registered at 10.00 AM (p<0.05 vs. 8.00 AM and 2.00 PM and p<0.01 vs. 4.00 PM). Cortisol did not show significant differences. In dogs with PDH, ACTH was lower at 8.00 AM (ACTH: p<0.01 vs. 2.00 and 4.00 PM; and p<0.05 vs. 6.00 PM). The lowest cortisol concentration was registered at 8.00 AM and 8.00 PM and the highest at 4.00 PM (p<0.05 vs. 8.00 AM and p<0.01 vs. 8.00 PM). After treatment, the lowest ACTH concentration was registered at 10.00 AM (p<0.01 vs. 2.00 and 4.00 PM). To conclude, the adrenal is desensitized in PDH possibly showing negative in diagnostic tests.

Cushing's disease in dogs: cabergoline treatment.

The treatment of pituitary-dependent hyperadrenocorticism (PDH) in dogs has for a long time been focused on inhibiting the adrenal gland using drugs such as o-p'-DDD, Ketoconazole and Trilostane, without attacking the primary cause: the corticotrophinoma. Corticotroph cells can express the D2 dopaminergic receptor; therefore cabergoline (Cbg) could be effective as a treatment. Follow-up over 4 years was carried out in 40 dogs with PDH that were treated with Cbg (0.07 mg/kg/week. Out of the 40 dogs, 17 responded to Cbg (42.5%). A year after the treatment, there was a significant decrease in ACTH (p<0.0001), alpha-MSH (p<0.01), urinary cortisol/creatinine ratio (p<0.001), and of the tumor size (p<0.0001) evaluated by nuclear magnetic resonance. Dogs responding to Cbg lived significantly longer (p<0.001) than those in the control group. To conclude, Cbg is useful in 42.5% of dogs with PDH, justifying its use as a treatment.

Natural estrous cycle in normal and diabetic bitches. II). Serum nonesterified fatty acids and serum free glycerol levels during glucose and insulin tests.

Actions and interactions of spontaneous diabetes mellitus (DM) and natural estrous cycles (sex seasons) on the regulation of serum nonesterified fatty acids (NEFAs) and free glycerol (FG) levels in bitches in the fasting condition and during i.v. glucose (IVGTT) and insulin (ITT) tolerance tests, were studied. DM increased serum NEFAs concentration both in the basal condition and during IVGTT; it provoked a fall response to glucose load which is absent in normal controls. Estrous cycles did not modify these observations. Serum NEFAs levels during ITT were unresponsive in normal and diabetic bitches at every sex stage; flat, overlapped serum NEFAs profiles were then observed except for the diabetic group at A, which showed an early abrupt fall response of this variable from its high base line. DM increased also serum FG concentration in the fasting condition and during IVGTT. In the normal controls, serum FG base line was not affected by sex status; similarly shaped, increasing, overlapped curves during the test were observed. In the diabetic bitches "in season" (either phase), serum FG basal value was hardly above in respect to anestrous, but during IVGTT their flat profiles coincided. DM increased serum FG concentration in the basal condition and during ITT, and modified the profiles of this variable. In normal dogs in the basal condition, serum FG concentration remained unaffected by sex status; this variable hard, transiently increased during ITT, which was not influenced by "sex seasons"; therefore, similarly shaped, overlapped serum FG profiles were then observed. In the normal and diabetic bitches, serum-FG base line was not changed by "sex seasons". During ITT, serum FG mean profile in the diabetic bitches at EP was modestly above that observed in those at LP; differences for any other comparisons in normals or diabetic bitches were nonsignificant. As reported by us elsewhere, impaired glucose metabolism and absolute insulin deficiency induced ketose-prone, acidotic, insulin-dependent diabetic chryses in certain normal and diabetic beaches "in season" studied here. The unability of these animals for hydrolizing glyceride-glycerol via lipoproteinlipase (IVGTT) or via hormone sensitive fractions of lipase (ITT) and the abolished serum NEFAs suppressibility during modest hiperinsulinemia (ITT) appear to contribute to the production of such chryses. Results are discussed on the basis of interactions of serum NEFAs and FG with respective blood sugar and serum immunoreactive insulin levels as influenced by DM and estrous cycle.

Natural estrous cycle in normal and diabetic bitches. II) serum nonesterified fatty acids and serum free glycerol levels during glucose and insulin tests

Actions and interactions of spontaneous diabetes mellitus (DM) and natural estrous cycles (sex seasons) on the regulation of serum monesterified fatty acids (NEFAs) and free glycerol (FG) levels in bitches in the fasting condition and during i.v. glucose (IVGTT) and insulin (ITT) tolerance tests, were studied. DM increased serum NEFAs concentration both in the basal condition and during IVGTT; it provoked a fall response to glucose load which is absent in normal controls. Estrous cycles did not modify these observations. Serum NEFAs levels during ITT were unresponsive in normal and diabetic bitches at every sex stage; flat, overlapped serum NEFAs profiles were then observed except for the diabetic group at A, which showed an early abrupt fall response of this variable from its high base line. DM increased also serum FG concentration in the fasting condition and during IVGTT. In the normal controls, serum FG base line was not affected by sex status; similary shaped, increasing, overlapped curves during the test were observed. In the diabetic bitches "in season" (either phase), serum FG basal value was hardly above in respect to anestrous, but during IVGTT their flat profiles coincided. DM increased serum FG concentration in the basal condition and during ITT, and modified the profiles of this variable. In normal dogs in the basal condition, serum FG concentration remained unaffected by sex status; this variable hard, transiently increased during ITT, which was not influenced by "sex seasons"; therefore, similarly shaped, overlapped serum FG profiles were then observed. In the normal and diabetic bitches, serum FG base line was not changed by "sex seasons". During ITT, serum FG mean profile in the diabetic bitches at EP was modestly above that observed in those at LP; differences for any other comparisions in normals or diabetic bitches were nonsignificant. As reported by us elsewhere, impaired glucose metabolism and absolute insulin dificiency induced ketose-prone, acidotic, insulin-dependent diabetic chryses in certain normal and diabetic beaches "in season" studied here. The unability of these animals for hydrolizingglyceride-glycerol via lipoproteinlipase (IVGTT) or via hormone sensitive fractions of lipase (ITT) and the abolished serum NEFAs suppressibility during modest hiperinsulinemia (ITT) appear to contribute to the production of such chryses...

Natural estrous cycle in normal and diabetic bitches. II) serum nonesterified fatty acids and serum free glycerol levels during glucose and insulin tests

Actions and interactions of spontaneous diabetes mellitus (DM) and natural estrous cycles (sex seasons) on the regulation of serum monesterified fatty acids (NEFAs) and free glycerol (FG) levels in bitches in the fasting condition and during i.v. glucose (IVGTT) and insulin (ITT) tolerance tests, were studied. DM increased serum NEFAs concentration both in the basal condition and during IVGTT; it provoked a fall response to glucose load which is absent in normal controls. Estrous cycles did not modify these observations. Serum NEFAs levels during ITT were unresponsive in normal and diabetic bitches at every sex stage; flat, overlapped serum NEFAs profiles were then observed except for the diabetic group at A, which showed an early abrupt fall response of this variable from its high base line. DM increased also serum FG concentration in the fasting condition and during IVGTT. In the normal controls, serum FG base line was not affected by sex status; similary shaped, increasing, overlapped curves during the test were observed. In the diabetic bitches "in season" (either phase), serum FG basal value was hardly above in respect to anestrous, but during IVGTT their flat profiles coincided. DM increased serum FG concentration in the basal condition and during ITT, and modified the profiles of this variable. In normal dogs in the basal condition, serum FG concentration remained unaffected by sex status; this variable hard, transiently increased during ITT, which was not influenced by "sex seasons"; therefore, similarly shaped, overlapped serum FG profiles were then observed. In the normal and diabetic bitches, serum FG base line was not changed by "sex seasons". During ITT, serum FG mean profile in the diabetic bitches at EP was modestly above that observed in those at LP; differences for any other comparisions in normals or diabetic bitches were nonsignificant. As reported by us elsewhere, impaired glucose metabolism and absolute insulin dificiency induced ketose-prone, acidotic, insulin-dependent diabetic chryses in certain normal and diabetic beaches "in season" studied here. The unability of these animals for hydrolizingglyceride-glycerol via lipoproteinlipase (IVGTT) or via hormone sensitive fractions of lipase (ITT) and the abolished serum NEFAs suppressibility during modest hiperinsulinemia (ITT) appear to contribute to the production of such chryses...(AU)

Natural estrous cycle in normal and diabetic bitches. II). Serum nonesterified fatty acids and serum free glycerol levels during glucose and insulin tests.

Actions and interactions of spontaneous diabetes mellitus (DM) and natural estrous cycles (sex seasons) on the regulation of serum nonesterified fatty acids (NEFAs) and free glycerol (FG) levels in bitches in the fasting condition and during i.v. glucose (IVGTT) and insulin (ITT) tolerance tests, were studied. DM increased serum NEFAs concentration both in the basal condition and during IVGTT; it provoked a fall response to glucose load which is absent in normal controls. Estrous cycles did not modify these observations. Serum NEFAs levels during ITT were unresponsive in normal and diabetic bitches at every sex stage; flat, overlapped serum NEFAs profiles were then observed except for the diabetic group at A, which showed an early abrupt fall response of this variable from its high base line. DM increased also serum FG concentration in the fasting condition and during IVGTT. In the normal controls, serum FG base line was not affected by sex status; similarly shaped, increasing, overlapped curves during the test were observed. In the diabetic bitches [quot ]in season[quot ] (either phase), serum FG basal value was hardly above in respect to anestrous, but during IVGTT their flat profiles coincided. DM increased serum FG concentration in the basal condition and during ITT, and modified the profiles of this variable. In normal dogs in the basal condition, serum FG concentration remained unaffected by sex status; this variable hard, transiently increased during ITT, which was not influenced by [quot ]sex seasons[quot ]; therefore, similarly shaped, overlapped serum FG profiles were then observed. In the normal and diabetic bitches, serum-FG base line was not changed by [quot ]sex seasons[quot ]. During ITT, serum FG mean profile in the diabetic bitches at EP was modestly above that observed in those at LP; differences for any other comparisons in normals or diabetic bitches were nonsignificant. As reported by us elsewhere, impaired glucose metabolism and absolute insulin deficiency induced ketose-prone, acidotic, insulin-dependent diabetic chryses in certain normal and diabetic beaches [quot ]in season[quot ] studied here. The unability of these animals for hydrolizing glyceride-glycerol via lipoproteinlipase (IVGTT) or via hormone sensitive fractions of lipase (ITT) and the abolished serum NEFAs suppressibility during modest hiperinsulinemia (ITT) appear to contribute to the production of such chryses. Results are discussed on the basis of interactions of serum NEFAs and FG with respective blood sugar and serum immunoreactive insulin levels as influenced by DM and estrous cycle.

Natural estrous cycle in normal and diabetic bitches. Basal serum total lipids and cholesterol. Serum triglycerides profiles during glucose and insulin tests.

All mean basal serum, total, cholesterol and lipids (L) levels in both fasted, normal bitches and in bitches with natural diabetes mellitus (DM) at anestrous (A) and during estrous cycle were measured. Mean serum, total triglycerides (TG) concentration in these animals at the same sex, stages, fasted and during intravenous glucose (IVGTT) and insulin (ITT) tolerance tests, were studied. In normal and in diabetic bitches serum cholesterol mean basal level differed significantly; the occurrence of estrous cycles (either phase) failed to affect these levels; DM and estrous cycle did not interact significantly. As for L, the influences of group and phase of estrous cycle on this variable significantly interacted. DM raised the mean basal level of this variable, in the normal group, "sex seasons" occurrence did not affect it whereas in the diabetic animals "in seasons" (either phase) it was above as compared with that found in respective controls at A. Estrogenic and luteal phases (EP, LP) did not differ in this concern. DM raised the mean serum TG levels in the bitches in the fasting condition and also during both tests; sex cycles action is variable. During IVGTT and ITT, the mean serum TG levels were influenced by sex stages and also by time elapsed either from glucose or insulin load. Thus, in the normal group, sex cycling did not vary significantly the TG profile during IVGTT. In the normal bitches "in season" (either phase), serum TG profile at the end of ITT increased more intensely than in the dogs at sex rest. During IVGTT, in the diabetic bitches, this profile was below base line from 15 min after glucose load till the test was over. DM intensely increased the serum TG response to insulin load in the bitches at A whereas such response was moderately decreasing at the end of ITT in the diabetic bitches at LP. All these results are discussed on the bases of the current knowledge on action of endocrine and metabolic products on these variables in normal animals, and the unability of these products to explain themselves the acute, severe, diabetic chryses observed during the LP of estral cycle in diabetic bitches or even in certain normal dogs at this moment of their "season", when diabetic outset uses to occur.

Natural estrous cycle in normal and diabetic bitches in relation to glucose and insulin tests.

The influence of spontaneous "sex seasons" on blood sugar (BS) and serum insulin levels was studied in bitches with natural diabetes mellitus (DM) and normal controls, in the basal condition and during glucose and insulin tests, was studied. DM increased basal BS, reduced glucose tolerance, distribution space (DS) and clearance from blood, and induced resistance to insulin hypoglycemic action. In normals occurrence of "seasons", inconsistently modified basal BS, increased glucose tolerance and DS; during estrogenic phase (EP), these variables were above those during luteal phase (LP). In diabetics at LP, BS found in lasting condition and during glucose test were higher than in diabetic bitches at EP (respective values at anestrous (A) in between) and glucose DS was smaller. Rate of glucose clearance from blood remained unaffected by "seasons" in both dog groups. Basal serum IRI was not modified by DM or "seasons". In normals, serum IRI response to glucose load was nonsignificant during A and increased during the "seasons"; either insulin DS or the rate of insulin clearance from blood stream remained unchanged under the circumstances, the increase being mediated by insulin secretion. During EP, the increase was particularly intense and mean insulinogenic index (MII) rose. During LP, MII returned to A value, whereby diabetic states might be manifest. Serum IRI profiles during insulin test were not modified by "seasons" in normal bitches; such response in diabetic bitches was intense during A, then decreased (EP) or was later abolished (LP). Either in normal or diabetic bitches, the sensitivity to exogenous insulin hypoglycemic action remained unchanged in spite of "seasons". In diabetic bitches at A, serum IRI after glucose challenge peaked higher than in respective normal controls (insulin clearance and insulin DS were similar): they exhibited relative insulin shortage and resistance to insulin hypoglycemic action partly compensated by promoted insulin secretion. Along with "season", abolished serum IRI response to glucose load in diabetics was observed. During EP, extrapancreatic factors regulating serum IRI concentration and MII did not change in respect to A, whereby abolishment appears mediated by depressed insulin secretion. During LP, insulin antagonism in conjunction with 1) absolute insulin deficiency and 2) intense decrease in MII appears as a powerful factor exposing diabetic bitches to a severe or fatal derangement in diabetic disease.

Lacrimomimetic effect of topical cyclosporine a in canine keratoconjunctivitis

Realizou descriçäo dos resultados obtidos com o uso tópico da Ciclosporina A em casos clínicos de ceratoconjuntivite seca em cäes. Observam que em todos os casos tratados houve o aumento dos valores da prova de Schirmer, melhora marcada do estado clínico dos olhos e depositado sobre a córnea