Diabetes (db/db) mutation-induced endometrial epithelial lipoapoptosis: Ultrastructural and cytochemical analysis of reproductive tract atrophy

BACKGROUND: The diabetes (db/db) mutation in C57BL/KsJ mice promotes a progressive cytolipidemia within the endometrial epithelial (EE) layer of the female reproductive tract which results in premature cellular and organ atrophy. The current studies focus on the ultrastructural and cytochemical changes which promote nuclear apoptosis and cytostructural disruption following the expression of endometrial hypercytolipidemia which promotes diabetes-associated organoinvolution and manifest infertility. METHODS: Control (normal:+/+) and diabetes (db/db) genotype groups were prepared for high resolution light microscopic analysis of cytolipidemia and nuclear apoptosis (TUNEL-labeled 3'-DNA fragmentation) indices and compared to the transmission electron (TEM) microscopic analysis of endometrial tissue samples collected from 8–16 week-old groups. RESULTS: Compared to controls, db/db mutation expression induced a dramatic increase in EE cytolipid vacuole volume and density within the epithelial endometrial layer. TEM analysis revealed that cytolipid vacuole accumulations initially aggregated at the baso-polar regions of UEE cells in response to the systemic hyperglycemic/hypertriglyceridemic conditions which characterized the (db/db) groups. Progressive cytoplasmic movement of the lipid pools into perinuclear compartments of affected EE cells induced nuclear isolation from organelles that were displaced towards peripheral cytoplasmic compartments. Cytochemical analysis of lipid vacuole accumulations indicated attraction towards, and incorporation within, the nuclear envelope of hyperlipidemic cells. Co-localization of nuclear apoptotic 3'-DNA fragments within identified hyperlipidemic EE cells was coincident with the cytochemical and ultrastructural identification of lipid penetration through the nuclear envelope in db/db mutants. CONCLUSION: These results are the first cytochemical indication that the metabolic disturbances in db/db mutants which promote hypercytolipidemia are coincident with lipoapoptosis-induced nuclear dissolution, as denoted by DNA fragmentation analysis. The lipidemia-induced alterations in intracellular organelle and nuclear architectures suggests that the metabolic disturbances in glucose and lipid metabolic cascades in diabetes (db/db) mutants disrupts cytointegrity, culminating in nuclear disregulation (as indicated by lipoapoptosis) and eventual premature reproductive tract organoinvolution and resultant, manifest, reproductive sterility

Habitat Utilization and Movement Ecology of Black Bears in Cherokee National Forest

Home range, movements, and habitat use of black bears in the Cherokee National Forest were monitored from June 1980 through December 1981. In 1980, home range sizes averaged 192 km2 for male bears and 23 km2 for females, whereas the average range in 1981 for males was 60 km2 and 15 km2 for females. Larger ranges for males likely reflect a social structure that enhances reproduction. Differences in home range sizes between years was attributed to the availability and abundance of hard mast, especially acorns. Both sexes exhibited seasonal shifts in range use between summer and fall. Males traveled greater distances between summer and fall ranges than female bears. Diel movements were affected by time of year, different foraging strategies between seasons, and mating activities. Both sexes moved greater distances in diurnal periods than nocturnal periods. Nocturnal movements were extensive only during fall. Increased nocturnal movements in fall were associated with seasonal changes in food sources, preparation for denning, and the influence of human-related activities. Bears exhibited crepuscular patterns of activity that were modified seasonally. Activities of bears were affected by weather factors, distribution and availability of foods, seasonal changes in foraging strategies, and denning. Sex, age, and reproductive classes also affected activity patterns. Adult male bears were the most active group, whereas females with cubs were the least active. The pattern of activity for bears in the CNF suggests that breeding may occur in early August. Factors affecting habitat use included season, individual behavioral differences among bears, reproductive classes, and variations in hard mast production between years. Occurrence of bears in hardwoods increased significantly during 1980 when acorns and hickory nuts were scarce. Habitat preference was also determined by a utilization-availability analysis. Hardwoods were preferred, although some variations in habitat use were sex related. Male bears used hardwoods (chiefly oaks) more than expected in terms of their availability, whereas females occurred more than expected in softwoods (chiefly pines)

Influences of obese (ob/ob) and diabetes (db/db) genotype mutations on lumber vertebral radiological and morphometric indices: Skeletal deformation associated with dysregulated systemic glucometabolism

BACKGROUND: Both diabetes and obesity syndromes are recognized to promote lumbar vertebral instability, premature osteodegeneration, exacerbate progressive osteoporosis and increase the propensity towards vertebral degeneration, instability and deformation in humans. METHODS: The influences of single-gene missense mutations, expressing either diabetes (db/db) or obese (ob/ob) metabolic syndromes on vertebral maturation and development in C57BL/KsJ mice were evaluated by radiological and macro-morphometric analysis of the resulting variances in osteodevelopment indices relative to control parameters between 8 and 16 weeks of age (syndrome onset @ 4 weeks), and the influences of low-dose 17-B-estradiol therapy on vertebral growth expression evaluated. RESULTS: Associated with the indicative genotypic obesity and hyper-glycemic/-insulinemic states, both db/db and ob/ob mutants demonstrated a significant (P ≤ 0.05) elongation of total lumbar vertebrae column (VC) regional length, and individual lumbar vertebrae (LV1-5) lengths, relative to control VC and LV parameters. In contrast, LV1-5 width indices were suppressed in db/db and ob/ob mutants relative to control LV growth rates. Between 8 and 16 weeks of age, the suppressed LV1-5 width indices were sustained in both genotype mutant groups relative to control osteomaturation rates. The severity of LV1-5 width osteosuppression correlated with the severe systemic hyperglycemic and hypertriglyceridemic conditions sustained in ob/ob and db/db mutants. Low-dose 17-B-estradiol therapy (E2-HRx: 1.0 ug/ 0.1 ml oil s.c/3.5 days), initiated at 4 weeks of age (i.e., initial onset phase of db/db and ob/ob expressions) re-established control LV 1–5 width indices without influencing VC or LV lengths in db/db groups. CONCLUSION: These data demonstrate that the abnormal systemic endometabolic states associated with the expression of db/db and ob/ob genomutation syndromes suppress LV 1–5 width osteomaturation rates, but enhanced development related VC and LV length expression, relative to control indices in a progressive manner similar to recognized human metabolic syndrome conditions. Therapeutic E2 modulation of the hyperglycemic component of diabetes-obesity syndrome protected the regional LV from the mutation-induced osteopenic width-growth suppression. These data suggest that these genotype mutation models may prove valuable for the evaluation of therapeutic methodologies suitable for the treatment of human diabetes- or obesity-influenced, LV degeneration-linked human conditions, which demonstrate amelioration from conventional replacement therapies following diagnosis of systemic syndrome-induced LV osteomaturation-associated deformations

Putting the Patient Back in Patient Care: Health Decision-Making from the Patient’s Perspective

This research explored health decision-making processes among people recently diagnosed with type 2 diabetes. Our analysis suggested that diagnosis with type 2 was followed by a period of intense emotional and cognitive disequilibrium. Subsequently, the informants were observed to proceed to health decision-making which was affected by three separate and interrelated factors: knowledge, self-efficacy, and purpose. Knowledge included cognitive or factual components and emotional elements. Knowledge influenced the degree of upset or disequilibrium the patient experienced, and affected a second category, agency: the informants’ confidence in their ability to enact lifestyle changes. The third factor, purpose, summarized the personal and deeply held reasons people gave as they made decisions concerning their health, eating and exercising. We propose this model, grounded in informant stories, as a heuristic, to guide further inquiry. From these stories, the patient is seen as more active and the interrelated influences of knowledge, agency, and purpose, synergistically interact to explain changes in health behaviors

TRANSformation; Affecting Transgender Prejudice in the Classroom

Social discrimination is a common experience with measurable consequences for those affected. The effects include poorer mental health and poverty, issues which are commonly addressed by human service professionals. People who are transgender are particular targets of discrimination and, as such, find themselves in need of human service assistance at levels disproportionate to the larger population. Research from social psychology suggests that intergroup contact reduces prejudice. This quasi-experiment explored the effect a transgender speaker, followed by informal social interaction, had on measures of transgender prejudice in a sample of college student

Modification of the Haag-Streit design slit-labp biomicroscope for ocular photography of the anterior and posterior segments

Modification of the Haag-Streit design slit-labp biomicroscope for ocular photography of the anterior and posterior segment

iBusy: Research on children, families, and smartphones

Within the past 10 years, mobile devices have been widely adopted by adults and are now present in the lives of almost all U.S. children. While phones are common, our understanding of what effect this technology has upon children\u27s development is lagging. Bioecological theory and attachment theory suggest that this new technology may be disruptive, especially to the degree to which it interferes with the parent-child relationship. This article reflects a National Organization for Human Services conference presentation and shares preliminary results from semi-structured interviews conducted with 18 youth, ages 7 through 11. Only four of eighteen interviewees voiced any negative thoughts concerning their parents’ use of mobile devices. However, those who reported feeling ignored by their parents experienced the negative emotions deeply. Themes that emerged from analysis of transcripts included devices as tools and boundaries

Different kinetics govern dopaminergic transmission in the amygdala, prefrontal cortex, and striatum: an in vivo voltammetric study

The regulation of extracellular dopamine (DA) concentrations was examined and compared in vivo in four projection fields of mesotelencephalic dopaminergic neurons with fast-scan cyclic voltammetry at carbon-fiber microelectrodes. Transient electrical stimulation of ascending DA fibers in a near physiological range of frequencies (10-20 Hz) elicited similar levels of extracellular DA in the medial prefrontal cortex (MPFC), basal lateral amygdaloid nucleus (BAN), caudate-putamen (CP), and nucleus accumbens (NAc) despite the documented 90-fold disparity in DA tissue levels and terminal density. However, marked differences were observed in the dynamics and overall frequency dependence of the evoked synaptic overflow of DA. These differences are due to the significantly different rates of release and uptake found in each of the four regions. For example, rate constants for the release of the four regions. For example, rate constants for the release and uptake of DA were similar in the MPFC and BAN but approximately 8 and 50 times less, respectively, than that in the CP and NAc. When the parameters were normalized to endogenous DA tissue content, a unique picture emerged: compared to all other regions, relative release was 10-fold greater in the MPFC while relative uptake was at least 10 times less in the BAN. The results further differentiate the functional characteristics of mesotelencephalic dopaminergic systems and demonstrate the regiospecific nature of DA neural transmission in the brain. In addition, the regulation of extracellular DA levels in the MPFC and BAN is suitable for the "long-range" transfer of chemical information in the brain and is consistent with a hypothesis of extrasynaptic neurotransmission

Estrogen Modulation of Uterine Adrenergic-Cholinergic Interaction: Effects on Vasoactivity and Adrenergic Receptors in the Guinea Pig1

ABSTRACT ABBREVIATIONS: UBF, uterine blood flow; NE, norepinephrine; DHA, dihydroalprenolol; DHE, dihydroergocryptine; OVX, ovanectomized; ACh, acetylchohine; 5-HT, 5-hydroxytryptamine

PII: S0166-2236(99)01425-3

Recent experimental findings show that fast synaptic transmission can extend its actions beyond the immediate synaptic cleft.Whether this phenomenon results in significant crosstalk between typical neighbouring synapses remains unclear. This article considers two areas of the hippocampus, the CA1 and dentate gyrus, where important neural processing occurs.The results discussed do not provide a simple answer to the question of whether synapses can 'talk' to their neighbours, but they do reveal crucial physiological constraints that determine the significance of synaptic crosstalk, thus adding considerably to our understanding of chemical synaptic transmission