Fur seal adaptations to lactation: insights into mammary gland function

The fur seal (Arctocephalus spp. and Callorhinus spp., members of the pinniped family) is a mammal with the unusual capability to modulate its lactation cycle by turning milk production on and off without the typical mammalian regression and involution of the mammary gland. Lactation has evolved from constraints arising from the spatial and temporal separation of infant nursing and maternal foraging as the mother gives birth and feeds the pup on land while acquisition of nutrients for milk production occurs at sea. The lactation cycle begins with the female fur seal undergoing a perinatal fast of approximately 1 wk, after which time she departs the breeding colony to forage at sea. For the remainder of the long lactation period (116–540 days), the mother alternates between short periods ashore suckling the young with longer periods of up to 4 wk of foraging at sea. Milk production continues while foraging at sea, but at less than 20% the rate of production on land. Fur seals produce one of the richest milk reported, with a very high lipid content contributing up to 85% of total energy. This feature serves as an adaptation to the young's need to produce an insulating blubber layer against heat loss and to serve as an energy store when the mother is away foraging at sea. This atypical pattern of lactation means mothers have long periods with no suckling stimulus and can transfer high-energy milk rapidly while on land to minimize time away from foraging grounds. The absence of suckling stimulus and milk removal during foraging does not result in the onset of involution with associated apoptosis of mammary secretory cells and a subsequent progressive breakdown of the cellular structure of the mammary gland. The mechanisms controlling lactation in the fur seal mammary gland have been investigated using molecular and cellular techniques. These findings have shed light on the processes by which the unique features of lactation in the fur seal are regulated.

Growth and development in a child with resistance to thyroid hormone and ectopic thyroid gland

Resistance to thyroid hormone is an uncommon problem, which has rarely been associated with thyroid dysgenesis. We report a case with both thyroid gland ectopy and resistance to thyroid hormone and, thus, a reduced capacity to produce and respond to thyroid hormone. The patient presented at 2 years of age with developmental delay, dysmorphic features, and elevation in both thyroxine and thyrotropin. We document her response to therapy with thyroxine, with particular regard to her growth and development. Persistent elevation of thyrotropin is commonly recognized during treatment of congenital hypothyroidism. Resistance to thyroid hormone may be an important additional diagnosis to consider in cases where thyrotropin remains persistently elevated.

Comparative analysis of caveolins in mouse and tammar wallaby: role in regulating mammary gland function.

Recent studies using the mouse showed an inverse correlation between the Caveolin 1 gene expression and lactation, and this was regulated by prolactin. However, current study using mammary explants from pregnant mice showed that while insulin (I), cortisol (F) and prolactin (P) resulted in maximum induction of the β-casein gene, FP and IFP resulted in the downregulation of Caveolin 1. Additionally, IF, FP and IFP resulted in the downregulation of Caveolin 2. Immunohistochemistry confirmed localisation of Caveolin 1 specific to myoepithelial cells and adipocytes. Comparative studies with the tammar wallaby showed Caveolin 1 and 2 had 70-80% homology with the mouse proteins. However, in contrast to the mouse, Caveolin 1 and 2 genes showed a significantly increased level of expression in the mammary gland during lactation. The regulation of tammar Caveolin 1 and 2 gene expression was examined in mammary explants from pregnant tammars, and no significant difference was observed either in the absence or in the presence of IFP.

Thyroid function testing in an inpatient mental health unit

OBJECTIVE: Thyroid function tests are a common screening investigation for patients admitted to a psychiatric inpatient unit. METHOD: This study aimed to retrospectively assess the clinical utility of routine thyroid function testing performed on newly admitted psychiatric patients over a 4-year period in Victoria, Australia via chart review of all abnormal results identified. RESULTS: Our retrospective audit revealed only two cases where identification of thyroid dysfunction informed patient management. In each case, the patient had a known history of thyroid disease. In this audit period, 893 patients required screening to yield one clinically relevant abnormal result, costing AU$24,975.57. CONCLUSION: Such low clinical utility does not support routine admission thyroid function tests for psychiatric inpatients. We conclude that thyroid function tests should only be performed where the history and clinical signs suggest a likely contribution of thyroid dysfunction to the psychiatric presentation.

The relationship between milk, mammary adipocytes and ECM in regulating murine mammary gland involution

 This thesis investigated the role of milk, extracellular matrix and mammary adipocytes in regulating mammary gland function during involution in mice and explored the use of an in vitro culture model, the mammosphere model system to study the same.

Changes in bacterial concentration in the liver correlate with that in the hepaticojejunostomy after bile duct reconstruction: implication in the pathogenesis of postoperative cholangitis

Postoperative cholangitis is a frequent and unpredictable complication of unknown etiology following bile duct reconstruction (BDR), particularly for biliary atresia. This study was undertaken to correlate the growth of bacteria in the hepaticojejunostomy with that in the liver after BDR. Quantitative bacterial culture was done on the specimens taken from the liver and from the hepaticojejunostomy at 1 week (group 1, n = 7), 1 month (group 2, n = 7), and 2 months (group 3, n = 7) following BDR with Roux-en-Y hepaticojejunostomy in piglets after 2 weeks of common bile duct ligation. The histological examination of the liver and the hepaticojejunostomy, as well as serial monitoring of hemogram and liver function tests, were performed to correlate the findings with the bacterial concentration of the liver and the hepaticojejunostomy following BDR. The bacterial concentration of the hepaticojejunostomy, expressed as log10 colony-forming units per gram (log10 CFU/g) of the hepaticojejunostomy, showed a progressive decrease from 8.38 ± 1.36 in group 1, 7.07 ± 2.54 in group 2, to 3.56 ± 1.31 in group 3 (p = 0.001). The log10 CFU/g of the liver also showed a progressive decrease from 5.02 ± 1.59 in group 1, 3.16 ± 1.56 in group 2, to 2.19 ± 1.09 in group 3 (p = 0.006). There was a significant positive correlation of the log10 CFU/g of the liver (n = 21) with that of the hepaticojejunostomy (n = 21) following BDR (r = 0.600, p = 0.004). Most of the infectious pathogens isolated from the liver were also isolated from the hepaticojejunostomy. The changes in hemoglobin, bilirubin, albumin, and ammonia significantly correlated with the changes of the bacterial concentration of the liver. The results of the study suggests that hepatic bacterial proliferation after BDR is significantly affected by microbial overgrowth in the bilioenteric anastomosis and is associated with deteriorated liver function and hemogram.

Benign recurrent intrahepatic cholestasis with secondary renal impairment treated with extracorporeal albumin dialysis

Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive condition characterized by intermittent episodes of pruritis and jaundice that may last days to months. Treatment is often ineffective and symptoms, particularly pruritis, can be severe. Extracorporeal albumin dialysis (molecular adsorbent recycling system, MARS) is a novel treatment which removes albumin bound toxins including bilirubin and bile salts. We describe a case of a 34-year-old man with BRIC and secondary renal impairment who, having failed standard medical therapy, was treated with MARS. The treatment immediately improved his symptoms, renal and liver function tests and appeared to terminate the episode of cholestasis. We conclude that MARS is a safe and effective treatment for BRIC with associated renal impairment.

A haemodialysis exercise program using novel exercise equipment

This study explored whether an exercise programme for haemodialysis patients, including the use of a purpose built dialysis exercise machine, would improve quality of life (QoL), nutrition, physical function and biochemical indices. QoL, and biochemical indices were measured at 6 months and nutrition was measured at 12 months. Physical function was measured at 4, 8 and 12 months. Results showed improvement in physical function tests a decrease in serum phosphate. The QoL health and physical functioning domain improved also. Conclusions The development of a structured exercise programme can improve quality of life, physical functioning, PO4 levels and urea clearances of dialysis patients.

Malondialdehyde plasma concentration correlates with declarative and working memory in patients with recurrent depressive disorder

Oxidative stress has been implicated in the cognitive decline, especially in memory impairment. The purpose of this study was to determine the concentration of malondialdehyde (MDA) in patients with recurrent depressive disorders (rDD) and to define relationship between plasma levels of MDA and the cognitive performance. The study comprised 46 patients meeting criteria for rDD. Cognitive function assessment was based on: The Trail Making Test , The Stroop Test, Verbal Fluency Test and Auditory-Verbal Learning Test. The severity of depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Statistically significant differences were found in the intensity of depression symptoms, measured by the HDRS on therapy onset versus the examination results after 8 weeks of treatment (P < 0.001). Considering the 8-week pharmacotherapy period, rDD patients presented better outcomes in cognitive function tests. There was no statistically significant correlation between plasma MDA levels, and the age, disease duration, number of previous depressive episodes and the results in HDRS applied on admission and on discharge. Elevated levels of MDA adversely affected the efficiency of visual-spatial and auditory-verbal working memory, short-term declarative memory and the delayed recall declarative memory. 1. Higher concentration of plasma MDA in rDD patients is associated with the severity of depressive symptoms, both at the beginning of antidepressants pharmacotherapy, and after 8 weeks of its duration. 2. Elevated levels of plasma MDA are related to the impairment of visual-spatial and auditory-verbal working memory and short-term and delayed declarative memory.

Laboratory features of common causes of fever in returned travelers

There can be considerable overlap in the clinical presentation and laboratory features of dengue, malaria, and enteric fever, three important causes of fever in returned travelers. Routine laboratory tests including full blood examination (FBE), liver function tests (LFTs), and C-reactive protein (CRP) are frequently ordered on febrile patients, and may help differentiate between these possible diagnoses.

Upregulation of sodium iodide symporter (NIS) protein expression by an innate immunity component: promising potential for targeting radiosensitive retinoblastoma

Retinoblastoma (RB), a malignant tumour of the eye arising from developing retina, is the most frequent primary intraocular malignancy of childhood. Its primary management with chemotherapy involves combination regimen of etoposide, vincristine and carboplatin and intra vitreal chemotherapy using melphalan when vitreous seeds develop. Radiotherapy is another effective mode in treating RB. We recently explored the notion if radiotherapy in RB can be mediated via Sodium Iodide Symporter (NIS), an intrinsic membrane glycoprotein which is a key regulator of iodide access to thyroid gland. Its expression has been exploited successfully for diagnostic imaging and molecular radionuclide-based therapy of thyroid cancer. We determined that NIS is expressed endogenously in RB tumour tissues, and in retinoblastoma cell lines Y79 and Weri-Rb-1, and therefore made an attempt to enhance the endogenously low expression of NIS protein in both Y79 and Weri-Rb-1 cells. Here we report about the potential of bovine lactoferrin (bLf) which is a known chemo preventive and emerging safe anti-cancer bio drug, as well as a natural transcriptional activator of genes, to enhance the endogenous expression of NIS in Y79 and Weri-Rb-1 cells. Real time PCR revealed that both cell lines express mRNA of lactoferrin receptors while flow cytometry and confocal microscopy showed the cells efficiently internalize bLf which upregulates NIS expression. These findings highlight an important step that could be taken towards the development of less harmful approaches for the treatment of RB by employing natural supplement bLf (with its clinically proven safe profile), and warrants further studies in future, focussing on enhancing NIS expression in RB cells and NIS functional assays in these cells.