Reliable observation of ECT-induced hormone release requires that other processes that affect hormone levels remain constant and not obscure it. This article reviews principles and pitfalls in making such observations. Clinical applicability and limitations of measurements of prolactin, cortisol, oxytocin, in vasopressin, and other hormones are described. Applications, include elucidation of ECT physiology and seizure quality, comparison of ECT techniques, and description of illness severity. Accounting for each of these different effects can be needed to characterize any of them. An important but unrealized application of neuroendocrine measurement is prediction of the stability of individual ECT response.

The gastrointestinal tract has a large functional reserve. This is particularly true of the small intestine, and early studies by Flint in 1912, showed that dogs could withstand 50%-70% small intestinal resection, returning to normal health after an initial period of weight loss and malabsorption. No doubt, this reserve is in part due to the very high rate of epithelial proliferation in small bowel mucosa. Intestinal adaptation is the result of morphological and functional changes, and while these parameters can be accurately appreciated, the mechanisms by which these changes take place, are still under active investigation. This section summarises the changes, both structural and functional, in the adaptive process, and this is followed by a review of the background work done on the possible mechanism of adaptation. The normal anatomy of intestinal mucosa is however, considered first. Most of the work done to date in the field of intestinal adaptation, involves the small bowel, and this part of the gut will be discussed predominantly, but data available on colonic growth will be mentioned.

No description available.

No description available.

Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2011 / Oestrogen receptor (ER) mutations have been identified for both ERα and ERβ in previous studies. The effects of the deletion variants due to splice mutations on clinical parameters, prognosis and treatment were examined in 61 breast carcinoma patients and 13 control samples from elective reduction mammoplasty procedures, respectively. RNA extracted from fine needle aspirates (FNAs) of breast tissue was reverse transcribed and using nested PCR and sequence analysis the presence of these variants elucidated. Using Χ2 and Fisher’s exact tests their significance with respect to clinical parameters such as tumour size, nodal involvement, stage, presence or absence of metastases, menstrual status and hormone responsiveness was examined. Kaplan-Meier survival analysis was also determined. The T-47D breast cancer cell line was cloned with two clones being selected for further analysis, namely TCA3 (hormone sensitive) and TCC1 (hormone resistant). These clones were treated for ten passages with oestrogen metabolites, 17-β- oestradiol and oestriol; oestrogen precursors, androstenedione and cholesterol; an anti-oestrogen, 4-hydroxy-tamoxifen; and the aromatase inhibitor aminoglutethimide, respectively. RNA was extracted from the cells initially and after the tenth passage and the ERα and ERβ exon profiles were examined using RT-PCR and sequence analysis. After the tenth passage hormone response tests were performed every 24 hours (up to 96 hours) with cell number being determined using the MTT assay. The results indicate that ERα and ERβ variants do not have any affect with respect to menstrual status and nodal involvement (N). Expression of ERα2 and ERα4 are required by the mouse monoclonal antibody (DAKO ® Clone 1D5) in the immunocytochemical assay used for the recognition of the protein in order to assess ER status and therefore show significance. ERαΔ2 and, contrary to previous investigations, the variant ERαΔ3 were not found to play a role in tumourigenesis. ERαΔ5 was observed to be more prevalent in ERα-positive patients and was usually co-expressed with the complete ERα5 indicating heterodimerization. ERαΔ5 showed no significance with respect to progression of disease or response to hormone treatment. An increase in the ratio of ERαΔ4: wild-type ERα4 indicated an increase in metastatic potential of diseased tissue. ERα4 and ERαΔ4 heterodimers were present in both T-47D clones and after 10 passages the TCA3 clone grown in 10-8M aminoglutethimide indicated a complete loss of ERα4 without altering hormone responsiveness. These results suggest that ERαΔ4 may play a role in progression of disease but not in the acquisition of tamoxifen resistance. ERαΔ6 was observed in 15% of patients but not in the T-47D clones or the control samples. An increase in the expression of ERαΔ6 among patient samples significantly increased their metastatic potential (p=0.018). ERαΔ6 was also observed as significant with respect to stage of disease (p=0.023) indicating the possible relevance of ERαΔ6 in progression of the disease. ERαΔ7 was the most frequently observed variant and did not show any significance with regard to any of the clinical parameters examined. The presence of ERαΔ7 did not show significance with regard to hormone response in vivo but in vitro the presence of this variant, expressed as a heterodimer with the wild-type ERα7, conferred greater sensitivity to tamoxifen in the tamoxifen resistant clone TCC1. Multiple exon deletions of ERα were also observed. The two more significant multiple deletion variants were those involving ERαΔ4, namely, ERαΔ2-ERαΔ6 and ERαΔ4-ERαΔ6. The multiple variant ERαΔ4-ERαΔ6 may be involved in tumour progression. ERβ variants were not examined in as much detail as ERα variants due to insufficient material available for analysis. The two domains, the DNA binding domain and the ligand binding domain, of ERβ were analyzed in a few of the patients and in the T-47D clones. They were not found to be significant with respect to the clinical parameters investigated and the ERβ profiles of the TCA3 and TCC1 clones remained unchanged after 10 passages under varying growth conditions.

Early life adversity (ELA) is a prevalent experience in young populations worldwide and can come in many forms, including limited access to resources as in many low socio-economic status households. ELA in humans has been linked to a variety of negative psychiatric outcomes including increased risk for psychiatric disorders such as schizophrenia, major depressive disorder (MDD), post-traumatic stress disorder (PTSD) and substance use disorder (SUD). One characteristic that these disorders share is a disruption in motivational processes. Motivation is largely regulated by the mesocorticolimbic dopamine (DA) system but is also modulated by other brain regions including the medial preoptic area (mPOA) and is crucial for processing of natural rewards such as sexual reproduction. This circuitry is sensitive to estrogenic and androgenic signaling in both males and females. Interestingly, estrogens and androgens can be modulated by the experience of ELA, pointing to gonadal hormones as a potential mediator for the impact of ELA on motivation and risk for psychiatric disorders. In the first set of experiments presented here, we characterize the limited bedding and nesting model (LBN) of early life adversity in rodents, in which rat dams and their pups are housed in a limited resource environment from postnatal day (PND) 2 through 9. LBN dams exhibited less self-care behaviors and more pup-directed behaviors, including grooming and nursing, compared to control dams. This type of maternal care is not characteristic of healthy rat dam behavior and may represent a compensatory mechanism to combat the lack of resources. However, LBN-raised pups still exhibit developmental alterations, notably a decrease in body weight that persisted into adulthood and an increase in adult plasma estradiol levels specifically in males. We build on these findings in the second set of experiments, which explores whether changes in development and gonadal hormones may also impact male reproductive behavior. We found that LBN males have a shorter latency to engage in sex behaviors at earlier timepoints in the sex assay compared to controls, suggesting an enhancement in the acquisition of this repertoire of behaviors. This enhancement in behavior was accompanied by highly sex-specific changes in gene transcription in the mPOA which underlies reproductive behaviors. The identification of genes and signaling pathways that are altered by LBN in the male mPOA lays the groundwork for future studies investigating the mechanisms by which ELA alters reproductive behaviors and underlying motivational processes. / Psychology

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No description available.

The Cape ground squirrel, Xerus inauris, is a highly social cooperative breeder that forms groups containing multiple breeding females. While the distribution of reproduction among group members is fairly even (i.e. exhibits low reproductive skew), previous studies of Cape ground squirrels suggest the reproductive development of sub-adult females is inhibited by the presence of adult breeding female group mates. As reproductive delay is known to be influenced by a number of different parameters, my goal was to determine if other factors affected the timing of sexual maturity, and if so, which factors are the most influential. In this study, I simultaneously test the relative power of seven different social and environmental parameters at explaining the variation in the female age of sexual maturity in two populations of Cape ground squirrels. Field work was conducted at two study sites in southern Africa, where trapping, behavioral and hormonal data were collected to determine the timing of reproductive development. Hormonal data was analyzed through the use of steroid enzyme immunoassay analysis to quantify the concentration of gonadal hormone in fecal samples which indicate the onset of sexual maturity. Prior to the start of the field season, I conducted an initial experiment to determine the best alternative form of fecal storage if freezing was unavailable. I found that drying feces provides a more reliable method for long-term preservation of fecal steroid concentrations when compared to storing fecal samples in alcohol. Data associated with each of the seven parameters was analyzed using model selection to simultaneously measure the ability of different combinations of parameters to explain the observed variation in female age of sexual maturity. I found that an increase in the number of adult breeding female group mates and related adult male group mates resulted in a substantial inhibition of female reproductive maturity. I concluded that a female Cape ground squirrel's age of sexual maturity is principally a result of the interaction between adult breeding females' capacity for reproductive suppression and sub-adults' ability to maximize lifetime reproductive success while minimizing inbreeding. The overall reproductive dynamics of each social group results from the tug-of-war between the adult and sub-adult female group mates to control breeding within the group, with minimal direct influence on sexual maturity by environmental factors.

Host-parasite relationships are one of the most common symbiotic relationships present in a diverse array of ecosystems. There are numerous factors that impact the dynamics of these relationships. Major factors that can influence the degree of parasitism include host sex, hormonal state, reproductive condition, and behavior. It has been observed in several vertebrate taxa that males have higher ectoparasite intensities than females and males with increased testosterone have increased ectoparasite intensities. One potential reason for these observations is that testosterone concentrations are elevated in males, particularly during the breeding season, and when circulating concentrations increase males become more vulnerable to ectoparasitism. Here I first tested the hypothesis that higher circulating testosterone concentrations in male western fence lizards (Sceloporus occidentalis) induce higher tick intensities. To examine this hypothesis I implanted male lizards with either testosterone or blank implants in the field. The testosterone-implanted males had significantly higher tick intensities compared to the control males. However, in contrast, control males had significantly higher mite intensities compared to testosterone-implanted males. These results are consistent with other studies suggesting that testosterone impacts certain aspects of host-parasite relationships. However, the exact mechanism for how testosterone influences parasite intensities remains unclear. There are two major current hypotheses for how testosterone influences ectoparasite intensities on males, the first involving immunosuppression and the second involving behavioral patterns and movement. However, another potential reason for why male lizards, particularly those with high circulating testosterone, have higher ectoparasite intensities than female and low testosterone male lizards is that the parasites preferentially choose their host. Furthermore, it has been demonstrated that vitellogenic female lizards have diminished immune function and this could potentially lead to increased ectoparasitism in much the same way that testosterone does in male lizards. Therefore, it is possible that a host preference is also present with vitellogenic versus non-vitellogenic female lizards. Although there have been a few interspecific studies done on this topic there have been no such studies on parasite host preference in reptiles to date. Here I tested three hypotheses: 1. Ticks prefer male lizards to female lizards. 2. Ticks prefer male lizards with high testosterone concentrations to male lizards with normal testosterone concentrations. 3. Ticks prefer vitellogenic female lizards to non-vitellogenic female lizards. All three experiments demonstrated no preference of host by ticks, which suggests they will attach to any suitable host they come across. However, during the male versus female host choice experiment ticks fed faster on vitellogenic female lizards than male lizards and non-vitellogenic female lizards. These results, taken together with previous studies showing higher tick intensities on male lizards, lizards with experimentally elevated testosterone, and reproductive female lizards, provide evidence that ticks do not preferentially choose their host, but instead are found in higher numbers on certain hosts due to some other reason. Other potential explanations include differences in immune function, microhabitat use, and behavioral patterns. One of the major hypotheses as to why male lizards, particularly those with high testosterone concentrations, have higher ectoparasite intensities than female lizards and male lizards with low testosterone concentrations is that these lizards perform more territorial behaviors, have increased movements, and larger home range sizes, thus exposing them to more parasites. Several studies have shown testosterone to increase the frequency of behaviors, movement, and home range size in lizards, but few, if any, have related it to ectoparasite intensities. Here I tested two hypotheses: 1. High testosterone male lizards have larger home ranges than male lizards with lower testosterone concentrations and female lizards. 2. High testosterone male lizards perform a higher frequency of territorial behaviors than male lizards with lower testosterone concentrations and female lizards. To test these hypotheses I implanted male lizards with either testosterone or blank-control implants, left female lizards unaltered, and performed behavioral observations in the field for 25 days. At the end of this time period, home range sizes were calculated as minimum convex polygons and ectoparasite intensities were quantified. Results of this study revealed no significant difference in ectoparasite intensities between high and low testosterone male lizards, but male lizards did have significantly higher ectoparasite intensities than female lizards. Furthermore, home range size and frequencies of territorial behaviors were not significantly different between high and low testosterone male lizards. However, male lizards did have larger home ranges and performed more territorial behaviors and movements than female lizards. These results suggest that home range, movement, and territorial behavior frequency contribute to higher ectoparasite intensities on male lizards, particularly those on males with high circulating testosterone. However, future studies need to address the behavioral and physiological mechanisms responsible for the observed effects of testosterone on parasitism, including parasite intensity, immunosuppression, and parasitic effects on host fitness.