Options for monitoring diabetic cats

The key to successful long-term management of diabetes in cats is individualization of advice to suit cat and owner. A relationship based on trust and cooperation between veterinarian and client leads invariably to the most satisfactory outcome. Success requires knowledge of the options for monitoring diabetic cats, selection and adaptation of appropriate techniques for each individual case, and provision of ongoing support and guidance for owners. The ongoing treatment of a diabetic cat can be one of the more rewarding experiences of feline practice, and many diabetic cats and their owners come to occupy a special place within the clinic environment. This chapter provides a comprehensive overview of the current options for monitoring diabetes in cats and guidelines for application of the techniques to clinical cases.

C-Peptide Levels and Insulin Independence Following Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation in Newly Diagnosed Type 1 Diabetes Mellitus

Context In 2007, the effects of the autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in 15 patients with type 1 diabetes mellitus (DM) were reported. Most patients became insulin free with normal levels of glycated hemoglobin A(1c) (HbA(1c)) during a mean 18.8-month follow-up. To investigate if this effect was due to preservation of beta-cell mass, continued monitoring was performed of C-peptide levels after stem cell transplantation in the 15 original and 8 additional patients. Objective To determine C-peptide levels after autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM during a longer follow-up. Design, Setting, and Participants A prospective phase 1/2 study of 23 patients with type 1 DM(aged 13-31 years) diagnosed in the previous 6 weeks by clinical findings with hyperglycemia and confirmed by measurement of serum levels of anti glutamic acid decarboxylase antibodies. Enrollment was November 2003-April 2008, with follow-up until December 2008 at the Bone Marrow Transplantation Unit of the School of Medicine of Ribeirao Preto, Ribeirao Preto, Brazil. Hematopoietic stem cells were mobilized via the 2007 protocol. Main Outcome Measures C-peptide levels measured during the mixed-meal tolerance test, before, and at different times following HSCT. Secondary end points included morbidity and mortality from transplantation, temporal changes in exogenous insulin requirements, and serum levels of HbA1c. Results During a 7- to 58-month follow-up (mean, 29.8 months; median, 30 months), 20 patients without previous ketoacidosis and not receiving corticosteroids during the preparative regimen became insulin free. Twelve patients maintained this status for a mean 31 months (range, 14-52 months) and 8 patients relapsed and resumed insulin use at low dose (0.1-0.3 IU/kg). In the continuous insulin-independent group, HbA(1c) levels were less than 7.0% and mean (SE) area under the curve (AUC) of C-peptide levels increased significantly from 225.0 (75.2) ng/mL per 2 hours pretransplantation to 785.4 (90.3) ng/mL per 2 hours at 24 months posttransplantation (P<.001) and to 728.1 (144.4) ng/mL per 2 hours at 36 months (P=.001). In the transient insulin-independent group, mean (SE) AUC of C-peptide levels also increased from 148.9 (75.2) ng/mL per 2 hours pretransplantation to 546.8 (96.9) ng/mL per 2 hours at 36 months (P=.001), which was sustained at 48 months. In this group, 2 patients regained insulin independence after treatment with sitagliptin, which was associated with increase in C-peptide levels. Two patients developed bilateral nosocomial pneumonia, 3 patients developed late endocrine dysfunction, and 9 patients developed oligospermia. There was no mortality. Conclusion After a mean follow-up of 29.8 months following autologous nonmyeloablative HSCT in patients with newly diagnosed type 1 DM, C-peptide levels increased significantly and the majority of patients achieved insulin independence with good glycemic control. Trial Registration clinicaltrials.gov Identifier: NCT00315133

A study of adrenocortical tumors in children and adolescents by a comparative genomic hybridization technique

Adrenocortical tumors (ACT) are rare neoplasms of the adrenal glands accounting for 0.2% of all pediatric cancers. However, the incidence of ACT in South Brazilian children is 10 to 15 times greater than the worldwide incidence. Comparative genomic hybridization studies have revealed the presence of a high degree of chromosomal instability in ACT. We evaluated 16 ACT, 8 of them carcinomas and 8 adenomas. The presence of changes in DNA copy numbers was determined by comparative genomic hybridization, and the findings were validated by real-time polymerase chain reaction on the basis of IGF-II gene expression. The adenomas showed a mean of 19.7 imbalances per case, with the most frequent gain and loss being 4p15.1-p15.3 and 20p11.2-p13.2, respectively. The carcinomas presented with a mean of 35.5 imbalances per case, with the more frequent gain being 2q14.1-q24.3 and the more frequent losses being 3q21-q26.2, 20q12-qter, and 22q11.2-q13.3. The most frequent imbalances in both adenomas and carcinomas were gains of 1p21-p31.2, 2p12-p21 and loss of 20p11.2-p12. The expression of IGF-II mRNA (11p15.5) was higher in samples that presented with a gain of this region. It has been established that great genomic instability exists in pediatric ACT.

Functional and bioinformatics analyses reveal conservation of Cis-regulatory elements between sciaridae and Drosophilidae

The sciarid DNA puff C4 BhC4-1 gene is amplified and transcribed in salivary glands at the end of the larval stage. In transgenic Drosophila, the BhC4-1 promoter drives transcription in prepupal salivary glands and in the ring gland of late embryos. A bioinformatics analysis has identified 162 sequences similar to distinct regions of the BhC4-1 proximal promoter, which are predominantly located either in 5` or 3` regions or introns in the Drosophila melanogaster genome. A significant number of the identified sequences are found in the regulatory regions of Drosophila genes that are expressed in the salivary gland. Functional assays in Drosophila reveal that the BhC4-1 proximal promoter contains both a 129 bp (-186/-58) salivary gland enhancer and a 67 bp (-253/-187) ring gland enhancer that drive tissue specific patterns of developmentally regulated gene expression, irrespective of their orientation.

Tc-99m-labeled dextran for mammary lymphoscintigraphy in dogs

Lymphoscintigraphy is the technique of choice for sentinel lymph node detection in women with early breast cancer, but there is limited information evaluating the value of this technique in animals. We investigated mammary lymphatic drainage in 25 young female mongrel dogs by intramammary injection of 18.5 MBq of Tc-99m-dextran (70,000 Da). Lymph node anatomical referencing was obtained using an external marker, bone scintigraphy, or scintiscanning the body contour. Cranial and caudal thoracic mammary glands drained into the cranial sternal lymph node and axillary lymph center. The cranial thoracic mammary gland also drained into the superficial cervical lymph node in two of five animals. The cranial abdominal gland was drained by the axillary lymph center. The caudal abdominal mammary gland was drained by the superficial inguinal lymph node in all animals and simultaneously by medial iliac lymph nodes in four of five animals. In one dog, this mammary gland was also drained by the mediastinal and the superficial cervical lymph nodes. The inguinal mammary gland was drained by superficial inguinal lymph nodes and simultaneously via the medial iliac lymph node in one animal. Lymphatic communications between lymph nodes were identified in 11 of 25 (44%) animals. Tc-99m-dextran mammary lymphoscintigraphy was easy and rapid to perform and may provide valuable information for further studies.

Macroscopic and microscopic anatomy of the oviduct in the sexually mature rhea (Rhea americana)

The morphological characteristics of the oviduct of 12 sexually mature rheas (Rhea americana) were studied. Only the left oviduct is developed as a long tube with a length of 122 +/- 23.1 cm, and is subdivided into infundibulum (15.2 +/- 4.0 cm), magnum (63.3 +/- 9.4 cm), isthmus (5.6 +/- 3.1 cm), uterus (16.0 +/- 4.2 cm) and vagina (11.5 +/- 1.4 cm). The mucous membrane of the oviduct, as a whole, possesses luminal folds covered by ciliated columnar epithelium with secretory cells. The infundibulum part presents a cranial opening with thin and long fimbriae with few tubular glands in caudal tubular portion. In the magnum, the largest portion of the oviduct, the folds are thicker and are filled with tubular glands. The isthmus is short and presents less bulky folds and a few tubular glands. A bag-shaped uterus in the cranial area shows thin folds, and in the caudal region (shell gland) more ramified folds with few tubular glands. The vagina has long luminal folds and a thick muscular tunic; no glands with sperm-storage characteristics have been observed. In conclusion, the oviduct in sexually mature rhea has morphological similarities with the other species of birds already described; however it presents its own characteristics to produce a big egg.

Morphologic study of the pineal gland of the dog

Following the discovery of the melatonin by Lerner et al. (1958), new research and perspectives were developed in order to improve the knowledge regarding the pineal gland. This hormone is not only related to the circadian control but also influences other behavioral functions such as the reproductive cycle and thermoregulation. In this study the morphology of the pineal gland (epiphysis cerebri) from 20 dogs were analyzed by means of macroscopic and microscopic evaluation. The shape of the gland ranged from conic to ""tongue-like shape"" (in relation to human tongue). The gland color ranged from beige to gray-brownish and it had a gelatinous consistency. The width and length of the glands ranged from 1.38 to 2.39 mm and 1.53 to 2.96 mm, respectively. Capsule, septa, pinealocytes, glial cells and pigment granules were microscopically found in all glands. No calcareous concretions were observed.

Light and scanning electron microcopy study of the tongue in Rhea americana

Morphological characteristics of the tongue were studied in adult rhea (Rhea americana). The lingual surface and the surface of epithelium-connective tissue interface of rhea tongue were examined macroscopically and by light and scanning electron microscopy. The rhea tongue revealed a triangular aspect, without adjustment of the inferior bill formation, occupying approximately of the length of the oral cavity. Lingual papilla-like structures were not observed over the lingual surface. The tongue mucosa was composed of a thick non-keratinized stratified squamous epithelium in the dorsal and ventral part, supported by a connective tissue core. The submucosa contained numerous glands with cytoplasmic granules, and luminal secretion was positive for histochemical reaction to Alcian Blue in pH 2.5 and PAS, and negative to Alcian Blue in pH 0.5. Despite the rudimentary characteristic of the tongue in rhea, our results suggest an important role of tongue secretions in food lubrication and humidification during the swallowing process, based on the enormous quantity of lingual glands in the submucosa and the histochemical characteristics of their secretions.

Intramammary infusion of leptin decreases proliferation of mammary epithelial cells in prepubertal heifers

High energy intake and excessive body fatness impair mammogenesis in prepubertal ruminants. High energy intake and excessive fatness also increase serum leptin. Our objective was to determine if an infusion of leptin decreases proliferation of mammary epithelial cells of prepubertal heifers in vivo. Ovine leptin at 100 mu g/quarter per d with or without 10 mu g of insulin-like growth factor (IGF)-I was infused via the teat canal into mammary glands of prepubertal dairy heifers; contralateral quarters were used as controls. After 7 d of treatment, bromodeoxyuridine was infused intravenously and heifers were slaughtered similar to 2 h later. Tissue from 3 regions of the mammary parenchyma was collected and immunostained for bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (Ki-67), and caspase-3. Leptin decreased the number of mammary epithelial cells in the S-phase of the cell cycle by 48% in IGF-I-treated quarters and by 19% in saline-treated quarters. Leptin did not alter the number of mammary epithelial cells within the cell cycle, as indicated by Ki-67 labeling. Caspase-3 immunostaining within the mammary parenchyma was very low in these heifers, but leptin significantly increased labeling in saline-treated quarters. Leptin enhanced SOCS-3 expression in IGF-I-treated quarters but did not alter SOCS-1 or SOCS-5 expression. We conclude that a high concentration of leptin in the bovine mammary gland reduces proliferation of mammary epithelial cells. The reduced proliferation is accompanied by an increase in SOCS-3 expression, suggesting a possible mechanism for leptin inhibition of IGF-I action. Whether leptin might be a physiological regulator of mammogenesis remains to be determined.

In vitro algaecide effect of sodium hypochlorite and iodine based antiseptics on Prototheca zopfii strains isolated from bovine milk

Prototheca zopfii has been considered one of the most important causes of environmental mastitis in Brazil. These algae are refractory to conventional therapy and cause great damage to the mammary gland. The present study evaluated the in vitro algaecide effect of sodium hypochlorite and iodine based antiseptics on 27 P. zopfii strains isolated from the milk of cattle. Low concentrations of sodium hypochlorite (0.0390625-0.15625%) and iodine (0.15625-0.625%) were effective against the isolates. These antiseptics may be recommended for hygiene routines, pre and postdipping and cauterization of bovine mammary glands infected by P. zopfii. (C) 2009 Elsevier Ltd. All rights reserved.

Effects of individual housing on behavior and resistance to Ehrlich tumor growth in mice

This study analyzed in Balb/C mice the effects of individual housing on behavior, serum corticosterone and resistance to Ehrlich tumor growth. Mice (60 days old) were individually (IH) or grouped housed (G) (10-12 animals/cage) for 14-21 days. The 1st day of the housing condition was considered experimental day 1 (ED1). Results showed that on ED21, IH mice, when compared to G mice, presented no differences on corticosterone serum levels when kept undisturbed; however, an increased level of this hormone was observed in IH mice after an immobilization stress challenge. An increased time spent in the plus-maze closed arms and a decreased time in the open arms were also observed in IH mice. When compared to G animals, after inoculation with 105 Ehrlich tumor cells on ED1, IH mice presented an increase in volume of ascitic fluid and number of tumor cells. The survival time of IH mice was also shorter than that measured in G animals. Furthermore, IH mice injected with a different number of tumor cells on ED1 always presented increased Ehrlich tumor cells than G group. Interestingly. these effects were not observed when the tumor cells injection was done on ED4. These results suggest that individual-housing conditions induce an altered immune-endocrine response and, at the same time, decrease animals` resistance to Ehrlich tumor growth. It is proposed that the neural link between the behavioral and immunological changes observed after the stress of individual housing might involve the activation of the HPA axis. (C) 2008 Elsevier Inc. All rights reserved.

Insulin Affects Tissue Organization and the Kinetics of Epithelial Cell Death in the Rat Ventral Prostate After Castration

Prostate growth and physiology are regulated by steroid hormones and modulated by multiple endocrine factors We investigated the action of insulin on the tissue organization and kinetics of epithelial cells in the rat ventral prostate (VP) in response to castration up to 120 hours after surgery by using an acute protocol of alloxan induced diabetes Diabetes caused a reduction in volume density (Vv(o)/) and volume of the epithelium The effects of castration on the epithelium were accelerated in the diabetic animals as determined by changes in V(o)/, and volume The smooth muscle cells became atrophic and apparently relaxed in response to castration in contrast to the spinous aspect observed in nondiabetic castrated rats Counting of apoptotic nuclei in the epithelium showed the classical apoptosis peak at 72 hours in nondiabetic rats and an advance of the apoptosis peak to 48 hours after castration in diabetic rats Insulin restored the time of the peak to 72 hours These results were confirmed after immunostaining for cleaved caspase 3 and suggest a survival and antiapoptotic effect on VP epithelial cells in both the presence and absence of androgen stimulation This idea is supported by the observation that insulin also reduced the overall rate of apoptosis at all experimental points analyzed before and after castration

Coordinated regulation of follicle development by germ and somatic cells

The continuum of folliculogenesis begins in the fetal ovary with the differentiation of the oogonia and their isolation within the primordial follicles. Primordial follicle activation is an enigmatic process, whereby some follicles enter the growing pool to become primary follicles, thereby embarking on an irreversible progression towards ovulation or atresia. This process is under the coordinated regulation of factors from the oocyte itself, as well as from the somatic cells of the ovary, in particular the theca and granulosa cells, which are structural components of the follicle. These two influences provide the principal stimuli for the growth of the follicle to the late preantral or early antral stage of development. The endocrine effects of the gonadotrophins FSH and LH are essential to the continued progression of the follicle and most atresia can be attributed to the failure to receive or process the gonadotrophin signals. The peri-ovulatory state has received intensive investigation recently, demonstrating a coordinated role for gonadotrophins, steroids, epidermal growth factor family proteins and prostaglandins. Thus, a complex programme of coordinated interaction of governing elements from both germ and somatic cell sources is required for successful follicle development.