Evaluation of different antiretroviral drug protocols on naturally infected feline immunodeficiency virus (FIV) cats in the late phase of the asymptomatic stage of infection.

The aim of this study was to evaluate the efficacy of the antiretrovirals: Zidovudine (ZDV) alone; ZDV + Recombinant Human Interferon-α (rHuIFN-α); ZDV + Lamivudine (3TC) and ZDV + valproic acid (Valp) on naturally feline immunodeficiency virus (FIV)-infected cats, in the late phase of the asymptomatic stage of infection. The follow-up was performed over one year, through clinical evaluation and the determination of viral loads and CD4+/CD8+ ratios. Neurological signs were studied by visual and auditory evoked potentials (VEP, AEP) and the responses were abnormal in 80% of the FIV-infected cats. After one year, an improvement in VEP and AEP was observed in the ZDV + Valp group and a worsening in the group receiving ZDV + rHuIFN-α. The CD4+/CD8+ ratio showed a significant increase (both intra and inter-groups) only in ZDV and ZDV + 3TC, between their pre-treatment and one year values, as well as among the other groups. Viral load only showed a significant decrease in ZDV and ZDV + 3TC groups, when comparing the values at one year of treatment vs. pre-treatment values and when the different groups were compared. In addition, the viral load decrease was significantly more pronounced in the ZDV + 3TC vs. ZDV group. We conclude that ZDV and ZDV + 3TC produce significant reductions in viral load and stimulate a recovery of the CD4+/CD8+ ratio, compared with the other protocols. It is clear that the addition of 3TC resulted in a greater reduction in viral load than use of ZDV as a single drug. Therefore, the combination ZDV + 3TC could be more effective than the sole use of ZDV.

Immune-endocrine interactions in treated and untreated cats naturally infected with FIV.

Feline immunodeficiency virus (FIV) is a lentivirus that causes a progressive disruption of immune function in cats. The neuroendocrine and immune systems communicate bidirectionally, mediated by cytokines such as tumour necrosis factor-α (TNF), several interleukins (IL-1, IL-6, IL-10), and through signals induced by the ratio of IL-10 to IL-12. FIV can affect both pituitary adrenal and thyroid axis function. Twenty FIV-infected cats in similar stages of the disease were evaluated for six months. A cross-sectional study in which the twenty cats were divided into two groups was performed. Ten were treated with Zidovudine (ZDV: 5mg/kg/d, PO, q12h, for six months) and 10 were untreated. Plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, T4, FT4, T3, IL-10, IL-12 and viral load (VL) were evaluated after six months. ACTH was found in significantly lower concentrations (p<0.0001) in the treated group whereas cortisol did not show significant differences between the two groups. Both T4 and FT4 had high values in untreated individuals (p<0.001) compared with Zidovudine treated cats. T3 did not show significant differences between the two groups. Both IL-10 and IL-12 were found in significantly higher concentrations in ZDV treated cats (p<0.001). By contrast, the IL10/IL-12 ratio values were significantly lower in untreated cats. Viral load was significantly lower in the treated cats after six months of therapy, compared with values detected pre-treatment (p<0.002). Untreated cats showed a significant increase of VL (p<0.04) compared with the values at the beginning of the study. In treated cats, VL showed lower numbers of viral copies than in untreated cats (p<0.01). In summary, Zidovudine treatment appeared to contribute to the normalization of both the adrenal and thyroid axes. This effect could be attributed to the decrease observed in VL, resulting in a change in cytokine patterns.

Serum insulin, glucose and non esterified fatty acids after administration of follicle-stimulating and luteinizing hormones in bitches.

This paper reports the effect of the simultaneous administration of follicle-stimulating (FSH) and luteinizing hormones (LH) on serum glucose, insulin and nonesterified fatty acid responses after glucose or insulin challenge. The animals were originally at anestrous. FSH (dose 2.5 U/kg body wt.) and LH (0.27 U/kg body wt.) were s.c. injected on days 1, 4, 8 and 11. Vaginal smears were obtained daily. Six untreated controls at anestrous and six treated bitches reaching proestrous were used. Glucose tolerance tests were done with a dose of 1 g of glucose per kg of body weight. Bovine insulin was administered at the dose of 0.25 U/kg body wt. During these tests, neither serum glucose and nonesterified fatty acids nor glucose distribution space and glucose clearance were affected by the treatment. The serum insulin response to hyperglycemia was greatly increased. The distribution space and clearance rate of this hormone were not affected by FSH + LH treatment. We conclude that, in the bitch, FSH + LH treatment, at doses that trigger "sex seasons", increases the serum insulin response to glucose load and produces a moderate resistance to the hypoglycemic, lipogenic and antilipolytic insulin actions. These phenomena are evident during hyperglycemia.

Serum insulin, glucose and non esterified fatty acids after administration of follicle-stimulating and luteinizing hormones in bitches.

This paper reports the effect of the simultaneous administration of follicle-stimulating (FSH) and luteinizing hormones (LH) on serum glucose, insulin and nonesterified fatty acid responses after glucose or insulin challenge. The animals were originally at anestrous. FSH (dose 2.5 U/kg body wt.) and LH (0.27 U/kg body wt.) were s.c. injected on days 1, 4, 8 and 11. Vaginal smears were obtained daily. Six untreated controls at anestrous and six treated bitches reaching proestrous were used. Glucose tolerance tests were done with a dose of 1 g of glucose per kg of body weight. Bovine insulin was administered at the dose of 0.25 U/kg body wt. During these tests, neither serum glucose and nonesterified fatty acids nor glucose distribution space and glucose clearance were affected by the treatment. The serum insulin response to hyperglycemia was greatly increased. The distribution space and clearance rate of this hormone were not affected by FSH + LH treatment. We conclude that, in the bitch, FSH + LH treatment, at doses that trigger [quot ]sex seasons[quot ], increases the serum insulin response to glucose load and produces a moderate resistance to the hypoglycemic, lipogenic and antilipolytic insulin actions. These phenomena are evident during hyperglycemia.

Serum insulin, glucose and non esterified fatty acids after administration of follicle-stimulating and luteinizing hormones in bitches

This paper reports the effect of the simultaneous administration of follicle-stimulating (FSH) and luteinizing hormones (LH) on serum glucose, insulin and nonesterified fatty acid responses after glucose or insulin challenge. The animals were originally at anestrous. FSH (dose 2.5 U/kg body wt.) and LH (0.27 U/kg body wt.) were s.c. injected on days 1, 4, 8 and 11. Vaginal smears were obtained daily. Six untreated controls at anestrous and six treated bitches reaching proestrous were used. Glucose tolerance tests were done with a dose of 1 g of glucose per kg of body weight. Bovine insulin was administered at the dose of 0.25 U/kg body wt. During these tests, neither serum glucose and nonesterified fatty acids nor glucose distribution space and glucose clearance were affected by the treatment. The serum insulin response to hyperglycemia was greatly increased. The distribution space and clearance rate of this hormone were not affected by FSH + LH treatment. We conclude that, in the bitch, FSH + LH treatment, at doses that trigger "sex seasons", increases the serum insulin response to glucose load and produces a moderate resistance to the hypoglycemic, lipogenic and antilipolytic insulin actions. These phenomena are evident during hyperglycemia (AU)

Serum insulin, glucose and non esterified fatty acids after administration of follicle-stimulating and luteinizing hormones in bitches

This paper reports the effect of the simultaneous administration of follicle-stimulating (FSH) and luteinizing hormones (LH) on serum glucose, insulin and nonesterified fatty acid responses after glucose or insulin challenge. The animals were originally at anestrous. FSH (dose 2.5 U/kg body wt.) and LH (0.27 U/kg body wt.) were s.c. injected on days 1, 4, 8 and 11. Vaginal smears were obtained daily. Six untreated controls at anestrous and six treated bitches reaching proestrous were used. Glucose tolerance tests were done with a dose of 1 g of glucose per kg of body weight. Bovine insulin was administered at the dose of 0.25 U/kg body wt. During these tests, neither serum glucose and nonesterified fatty acids nor glucose distribution space and glucose clearance were affected by the treatment. The serum insulin response to hyperglycemia was greatly increased. The distribution space and clearance rate of this hormone were not affected by FSH + LH treatment. We conclude that, in the bitch, FSH + LH treatment, at doses that trigger "sex seasons", increases the serum insulin response to glucose load and produces a moderate resistance to the hypoglycemic, lipogenic and antilipolytic insulin actions. These phenomena are evident during hyperglycemia

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 cycles 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 know ledge 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. (AU)

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 cycles 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 know ledge 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 fasting condition and during glucose test were higher than in diabetic biches 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 particulary 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 hypolgycemic action partly compensated by prometed 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 anatogonism 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. (AU)

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 fasting condition and during glucose test were higher than in diabetic biches 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 particulary 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 hypolgycemic action partly compensated by prometed 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 anatogonism 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.