Duration of treatment with progesterone and regression of persistent ovarian follicles in cattle

The objective of the present study was to determine the duration of elevated concentrations of progesterone necessary to induce atresia of persistent ovarian follicles. Heifers were administered 25 mg of PGF2alpha on d 6 and 7 (d 0 = d of synchronized estrus) and a norgestomet implant from d 6 to 14. Ovaries were monitored by ultrasonography, and blood samples were collected on d 3, 5, 7, 9, 11, and 12 and daily from d 14 until ovulation. On d 12, heifers received either two progesterone-releasing intravaginal devices (PRID) for 6 h (6-h; n = 5), two PRID for 24 h (24-h; n = 5), or no treatment (CON; n = 5). Blood samples were collected at 15-min intervals from h -6 to 30 (PRID insertion = h 0) and analyzed for concentrations of LH. Characteristics of LH secretion were determined for consecutive 6-h periods (Period 0 to 5). Hourly blood samples, collected from h 0 to 29, were analyzed for concentrations of 17beta-estradiol (estradiol) and progesterone. The dominant ovarian follicles present on d 7 increased in size to 15.4+/-.3 mm on d 12 ("persistent follicle"). Following removal of the PRID and norgestomet implants, atresia of persistent follicles and ovulation of new follicles were induced in one of five and in four of five heifers in the 6-h and 24-h treatments, respectively. Persistent follicles ovulated after withdrawal of norgestomet in all other heifers. Concentrations of progesterone were increased from h 1 to 7 in the 6-h and h 1 to 26 in the 24-h treatment. Frequency of LH pulses was reduced (P < .05) during Periods 1 to 2 in the 6-h and Periods 1 to 5 in the 24-h treatment relative to the CON treatment. By h 10, concentrations of estradiol in the 6-h and 24-h treatments were lower (P < . 05) than in the CON treatment. This suppression continued through h 29 in the 24-h treatment (P < .05), whereas concentrations in the 6-h treatment were intermediate to those of the CON and 24-h treatments after h 14. Suppression of pulsatile LH release and estradiol secretion was evident with 6 and 24 h of treatment with progesterone, but only the 24-h treatment induced atresia of persistent follicles in a majority of the heifers.     

Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography

BACKGROUND: Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post-mortem brain tissue of depressed patients. We sought to determine whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [123I] beta-CIT SPECT and platelet [3H]paroxetine binding. METHODS: Drug-free depressed and healthy subjects were injected with 211 +/- 22 MBq [123I] beta-CIT and imaged 24 +/- 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V3" = (brainstem-occipital)/occipital), a measure proportional to the binding potential (Bmax/Kd), was used for all comparisons. RESULTS: Results showed a statistically significant reduction in brainstem V3" values in depressed as compared to healthy subjects (3.1 +/- .9 vs. 3.8 +/- .8, p = .02). Platelet [3H]paroxetine binding was not altered (Bmax = 2389 +/- 484 vs. 2415 +/- 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [123I] beta-CIT binding (r = -0.14, p = .48). CONCLUSIONS: These data are the first to suggest reductions in the density of brain SERT binding sites in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression.     

The multifarious spectrum of ischemic left ventricular dysfunction: relevance of new ischemic syndromes

Ischemic heart disease, once limited to a number of well defined entities such as angina of effort, unstable angina, and myocardial infarction, must now be regarded as a much more complex and elusive entity. Silent ischemia was the first of the new ischemic syndromes to be described. Recently, three further new syndromes have been added, namely stunning, hibernation and preconditioning. All three have one common theme--they can be related to ischemia and reperfusion. In stunning, there is post-reperfusion mechanical dysfunction that recovers. In hibernation, there is prominent contractile dysfunction, apparently out of proportion to the reduction in coronary flow, and the recovery upon reperfusion is good. In preconditioning, severe ischemia followed by reperfusion protects against subsequent ischemia which may modify the severity of ischemic damage in the other ischemic syndromes. Ischemic LV dysfunction as found in post-infarct patients and in the absence of any simple relation to reperfusion, can be either diastolic or systolic or both in nature. In ischemic LV diastolic dysfunction without major systolic dysfunction, calcium antagonists may be appropriate therapy which could point to a role for abnormalities in the regulation of cytosolic calcium. It is proposed that there is potentially a mixed post-infarct syndrome, which may comprise one or more of the new ischemic syndromes (silent ischemia, stunning, hibernation, and preconditioning), as well as a varying degree of systolic and/or diastolic dysfunction. The basis of the systolic dysfunction is, at least in part, post-infarct LV remodeling. Several of these entities could overlap in the same patient. The term "mixed post-infarct ischemic syndrome" is suggested to describe this condition.     

The role of "indirect" recognition in initiating rejection of skin grafts from major histocompatibility complex class II-deficient mice

In vitro studies have revealed several pathways by which T cells can respond to alloantigens, including CD4+ direct responses to allogeneic class II antigens, CD8+ direct responses to allogeneic class I antigens, and CD4+ "indirect" responses to peptides of alloantigens presented in association with responder class II molecules. In vivo studies of skin graft rejection, however, have so far provided clear evidence for the contribution of only the two direct pathways and not for indirect recognition. We have used major histocompatibility complex class II-deficient mice as donors to test the role of indirect recognition in rejection of skin grafts. Class II-deficient skin was always rejected without delay by normal recipients. Removal of recipient CD8+ cells (to leave the animals dependent on CD4+ function) or depletion of recipient CD4+ cells revealed that CD4+ cells were usually involved and sometimes absolutely required in this rapid rejection. Since the donor grafts lacked class II antigens, the CD4+ cells must have recognized donor antigens presented in association with recipient class II molecules. These results therefore indicate that indirect recognition can initiate rapid skin graft rejection.     

Encoding Abstract Syntax Without Fresh Names

This paper introduces a variant of nominal abstract syntax in which bindable names are represented by normal meta-variables as opposed to a separate class of globally fresh names. Distinct meta-variables can be instantiated with the same concrete name, which we call aliasing. The possible aliasing patterns are controlled by explicit constraints on the distinctness (freshness) of names. This approach has already been used in the nominal meta-programming language ??ML. We recap that language and develop a theory of contextual equivalence for it. The central result of the paper is that abstract syntax trees (ASTs) involving binders can be encoded into ??ML in such a way that ??-equivalence of ASTs corresponds with contextual equivalence of their encodings. This is novel because the encoding does not rely on the existence of globally fresh names and fresh name generation, which are fundamental to the correctness of the pre-existing encoding of abstract syntax into FreshML.     

Evaluating overflow probability for voice over internet protocol buffer dimensioning

The provision of quality of service to different service types in broadband packet networks requires techniques for the evaluation of the probabilities of packet delays and loss. The authors analyse the multiplexing of independent and homogeneous Markovian ON-OFF traffic sources into a single buffer, extending earlier work. The resulting closed-form equation provides a virtually zero-complexity approach to the calculation of the buffer overflow probability via the burst-scale decay rate of the buffer state probabilities. Graphical results are provided, comparing our expression with the results from simulations and the -standard- formula of Anick, Mitra and Sondhi. These show that our new formula provides excellent accuracy for medium to high loads, i.e. those load values at which queuing becomes important. This makes it ideal for quick calculations, with practical utility when dimensioning checks are required in many networking situations involving the accurate estimation of loss probabilities in e.g. buffer multiplexing VoIP traffic sources.     

Modelling of the disulphide-swapped isomer of human insulin-like growth factor-1: implications for receptor binding

Insulin-like growth factor-1 (IGF-1) is a serum protein whichunexpectedly folds to yield two stable tertiary structures withdifferent disulphide connectivities; native IGF-1 [18–61,6–48,47–52]and IGF-1 swap [18–61,6–47, 48–52]. Here we demonstratein detail the biological properties of recombinant human nativeIGF-1 and IGF-1 swap secreted from Saccharomyces cerevisiae.IGF-1 swap had a ~30 fold loss in affinity for the IGF-1 receptoroverexpressed on BHK cells compared with native IGF-1.The parallelincrease in dose required to induce negative cooperativity togetherwith the parallel loss in mitogenicity in NIH 3T3 cells impliesthat disruption of the IGF-1 receptor binding interaction ratherthan restriction of a post-binding conformational change isresponsible for the reduction in biological activity of IGF-1swap. Interestingly, the affinity of IGF-1 swap for the insulinreceptor was ~200 fold lower than that of native IGF-1 indicatingthat the binding surface complementary to the insulin receptor(or the ability to attain it) is disturbed to a greater extentthan that to the IGF-1 receptor. A 1.0 ns high-temperature moleculardynamics study of the local energy landscape of IGF-1 swap resultedin uncoiling of the first A-region -helix and a rearrangementin the relative orientation of the A- and B-regions. The modelof IGF-1 swap is structurally homologous to the NMR structureof insulin swap and CD spectra consistent with the model arepresented. However, in the model of IGF-1 swap the C-regionhas filled the space where the first A-region -helix has uncoiledand this may be hindering interaction of Val44 with the secondinsulin receptor binding pocket.     

Role of cytosolic calcium balance on cell injury in cultured bovine aortic endothelial cells during hypoxia and reoxygenation]

The integration of pharmacological therapies for comorbid disorders requires an acceptance of independence and interactions of respective addictive and psychiatric disorders. At the same time, alcohol and other drugs induce psychiatric states that are indistinguishable from psychiatric disorders. On the other hand, while psychiatric disorders do not induce addictive use of alcohol and drugs, they do pose vulnerabilities to the development of addictive disorders. Generally, the treatment of comorbid disorders begins with abstinence and evaluation of the effects of alcohol and other drugs in contributing to the psychiatric picture. In the case of comorbid disorders, stabilization and standard treatments can be employed with certain cautions, namely, to avoid the use of addicting medications such as benzodiazepines and opiates beyond the detoxification stage. High potency neuroleptics and antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) can be used to treat continuing psychiatric states after the exclusionary criteria in DSM-IV for substance-related disorders have been applied to the clinical case. If the psychiatric symptoms clear with sustained abstinence, little or no medications may be required. Specific treatment of the addictive disorders will often determine the extent that addictive disorders are responsible for psychiatric symptomatology. Alternatively, treatment of the psychiatric disorder will enhance compliance with addiction treatment.