Effect of Continuous Infusion of Relaxin on Progesterone, Oxytocin, and Relaxin Blood Concentrations and Time of Parturition in Beef Heifers

These studies were designed to determine whether continuous intravenous infusion of increasing dosages of porcine relaxin during late pregnancy in beef heifers would influence circulating blood concentrations of relaxin, progesterone, and oxytocin, and time of onset of parturition. Beef heifers were bred by artificial insemination and, on Day 277, fitted with indwelling jugular cannulas for hormone infusion and blood sampling from Day 277 to 286. Intravenous infusion of purified porcine relaxin (pRLX, 3000 U mg-1) was started in heifers (n = 8) at increasing dosages (200 U h-1 on Days 277 and 278, 300 U h-1 on Days 279 and 280, 500 U h-1 on Day 281, 600 U h-1 on Day 282, and 700 U h-1 on Days 283 to 286). Phosphate buffer saline (PBS, 10 ml h-1) was infused during these same times to control (n = 6) animals. Relaxin treatment steadily increased the circulating plasma concentration of immunoreactive relaxin to more than 120 ng ml-1 compared with less than 0.5 ng ml-1 in PBStreated controls. Relaxin infusion in increasing dosages over the treatment time was associated with a significant decrease (P < 0.01) in plasma progesterone concentration compared with the PBS controls. Plasma levels of oxytocin at 4- hour intervals remained similar (P > 0.05) during the pretreatment period and throughout continuous infusion of pRLX and PBS. Although continuous intravenous infusion of relaxin resulted in a decrease in circulating blood levels of progesterone, it did not significantly reduce the interval between the beginning of pRLX treatment and parturition compared with the PBS-infused control heifers. These results indicate that continuous intravenous infusion of high levels of porcine relaxin resulted in a decrease in progesterone secretion in late pregnant beef heifers.

Correspondence of Gonadotropin-Releasing Hormone and Luteinizing Hormone Secretion during Suckling in Postpartum Cows

The hypothalamus in the lower part of the brain contains neurons that produce a small peptide, gonadotropin- releasing hormone (GnRH, LHRH), that regulates luteinizing hormone (LH) secretion by the anterior pituitary gland. Important functions of LH include induction of ovulation in preovulatory follicles during estrus and the luteinization of granulosa cells lining those collapsed follicles to form corpora lutea that produce progesterone during the luteal phase of the estrous cycle or during pregnancy. The production of progesterone by the corpus luteum conveys a negative feed-back action at the central nervous system (CNS) for further episodic secretion of GnRH and in turn, LH secretion. Gonadal removal (i.e., ovariectomy) allows a greater amount of LH secretion to occur during a prolonged period. The objectives of this study were to characterize the pattern of GnRH secretion in the cerebrospinal fluid (CSF) of the bovine third ventricle region of the hypothalamus, determine its correspondence with the tonic and surge release of LH in ovariectomized cows, and examine the dynamics of GnRH pulse release activity in response to known modulators of LH release (suckling, neuropeptide-Y [NPY]). In ovariectomized cows, both tonic release patterns and estradiol-induced surges of GnRH and LH were highly correlated. A 500-microgram dose of NPY caused an immediate cessation of LH pulses and decreased plasma concentrations of LH for at least 4 hours. This corresponded with a decrease in both GnRH pulse amplitude and frequency. In anestrous cows, GnRH pulse frequency did not change before and 48 to 54 hours after weaning on day 18 postpartum, but GnRH concentration and amplitudes of GnRH pulses increased in association with weaning and heightened secretion of LH. It is clear that high-frequency, highamplitude pulses of LH are accompanied by similar patterns of GnRH in CSF of adult cattle. Yet strong inhibitors of LH pulsatility, putatively acting at the level of the central nervous system (i.e., suckling) or at both the central nervous system and pituitary (NPY) levels, produced periods of discordance between GnRH and LH pulses.

Brain Regulation of Growth in Beef Calves

Small peptide hormones produced in the lower part of the brain (hypothalamus) regulate episodic and basal secretion of hormones from the anterior pituitary gland that affect metabolism and growth in cattle. This study focused on long-term growth in young calves subjected to hypophysectomy (HYPOX), hypophyseal stalk transection (HST), and sham operation control (SOC). Crossbred (Hereford x Aberdeen Angus) and Hereford, and Aberdeen Angus calves were HYPOX (n = 5), HST (n = 5), or SOC (n = 8) at 146 days of age, whereas another group was HST (n = 5) or SOC (n = 7) at 273 days of age. Body weight was determined every 21 days from birth to 1008 days of age. From day 146-1008, growth was arrested (P < 0.001) in HYPOX (0.06 kg/day) compared with SOC (0.50 kg/day) calves. Growth continued but at a significantly lower rate (P < 0.05) in calves HST at 146 days (0.32 kg/day) and 273 days (0.32 kg/day) compared with SOC (0.50 kg/day). Although episodic growth hormone (GH) secretion was abolished and peripheral blood serum GH concentration remained consistently lower in HST calves (2.4 ng/ml) than in the SOC (5.5 ng/ml; P < 0.01), the calves continued to grow throughout 1008 days. Peripheral serum thyroid stimulating hormone (TSH) concentration was less (P < 0.05) in HST compared with SOC calves. There was an abrupt decrease (P < 0.001) in serum thyroxine (T4) (4-fold) and triiodothyronine (T3) (3-fold) concentration after surgery that remained to 360 days in HST compared with SOC calves. At sacrifice, pituitary gland weight was markedly reduced (P < 0.001) in HST (0.18 g/100 kg body weight) compared with SOC (0.55 g/100 kg body weight) calves. Histological examination of pituitary glands from HST calves indicated the persistence of secretory GH and TSH cells in the same areas of the anterior pituitary gland as SOC calves. Coronal sections of the gland revealed GH and TSH secreting cells in HST calves that were similar to the controls. These results indicate that long-term growth continues, but at a slower rate, after hypophyseal stalk transection of immature calves in spite of complete abolition of episodic GH secretion and consistently decreased basal secretion of GH, TSH, T4, and T3 compared with sham-operated animals. Growth was abolished after hypophysectomy of immature calves in which circulating GH and TSH was undetectable.

Superovulation of Beef Heifers with Follicle Stimulating Hormone or Human Menopausal Gonadotropin: Acute Effects on Hormone Secretion

The effects of superovulatory treatment (follicle stimulating hormone [FSH] versus human menopausal gonadotropin [HMG]) and of route of administration (intramuscular versus intravenous) of prostaglandin F2a (PGF2a) on hormonal profiles were determined in 32 Angus x Hereford heifers for breeding and subsequent embryo collection and transfer. Heifers were superstimulated either with FSH (total of 26 milligrams) or HMG (total of 1,050 international units) beginning on days 9 to 12 of an estrous cycle and PGF2a (40 milligrams) was administered at 60 and 72 hours after the beginning of superovulatory treatments. Heifers were artificially inseminated three times at 12-hour intervals beginning 48 hours after PGF2a treatment. Blood serum samples were collected immediately before treatments began and at frequent intervals until embryo collection 288 hours later. Concentrations of luteinizing hormone (LH) and FSH were not affected by hormone treatments, route of PGF2a injection, or interactions between them. Estradiol-17ß (E2-17ß) levels were higher in HMG- than in FSH-treated heifers 60 hours after gonadotropin treatment. Peak concentration of E2-17ß occurred earlier in HMGthan in FSH-treated heifers and earlier in heifers injected with PGF2a intramuscularly than those injected intravenously. Progesterone concentrations were not influenced by treatment or route of PGF2a administration. The progesterone:E2-17ß ratio was higher in FSH- than in HMG-treated heifers 24 hours after the LH peak. The high steroid hormone concentrations in superovulated beef heifers before and after ovulation may lead to asynchrony between stages of embryonic development, a situation that may interfere with the pregnancy outcome of superovulated embryos in recipient animals.

Effects of Novel Growth Hormone Secretagogues on Growth Hormone Secretion in Farm Animals

The requirement for growth hormone (GH) secretion by the anterior pituitary gland in beef calves is demonstrated by a complete lack of long bone-growth and muscle accretion after hypophysectomy (surgical removal of the pituitary gland). When the connecting link (hypophyseal stalk) to the basal region (hypothalamus) of the brain is surgically severed, long bone growth and body weight gain are greatly limited compared with sham-operated controls. This limited growth results from obliteration of episodic GH secretion and reduced basal blood concentration of the hormone compared with sham-operated controls. Thus, the hypophyseal stalk-transected (HST) calf provides an appropriate model to determine mechanisms by which hypothalamic neuropeptides from the brain regulate GH secretion, and thereby growth in the young calf. Neuropeptides have been isolated and characterized in bovine hypothalamus that stimulate GH secretion (GH-releasing hormone [GHRH]) or factor [GHRF] and inhibit GH secretion (GH release-inhibiting hormone [GHRIH] or somatostatin [SRIH]). A dose of .067 micrograms of GHRF per kilogram of body weight injected intravenously in HST calves abruptly increased plasma GH concentration to 55 nanograms per milliliter from the control period mean of 5 nanograms per milliliter. HST calves then were infused intravenously with .033 and .067 microgram somatostatin per kilogram of body weight, during which a pulse injection of .067 microgram of GHRF was administered. GH increase was limited to 9 and 5 micrograms per kilogram body weight during the .033- and .067 microgram SRIH infusions after GHRF; no GH rebound was observed after the SRIH was discontinued. GHRF from humans contains 40 to 44 amino acids. Rat hypothalamic GHRF analogs containing 29 to 32 amino acids elicited dose-dependent GH peak release in these HST calves. In 1977, Bowers and Monomy isolated novel GH releasing peptides consisting of only six amino acids; they caused GH release by isolated pituitary cells in culture and acute GH release when administered intravenously. We recently have utilized a novel nonpeptidyl GH secretagogue of low molecular weight in the pig to determine its mechanisms of action within the central nervous system.

Role of the Central Nervous System in the Regulation of Pregnancy, Parturition and Lactation in Beef Heifers

Progesterone secretion is crucial for maintaining pregnancy to parturition in mammalian species, and in cattle the corpus luteum is the primary source of this hormone. This study determined the roles of prolactin (PRL), growth hormone (GH) and luteinizing hormone (LH) in the luteotropic process in beef heifers hypophyseal stalk-transected (HST, n = 7) or sham operated on (SOC, n = 9) during midgestation. The main finding was that endogenous PRL and GH maintained progesterone secretion in HST heifers similar to that in SOC throughout pregnancy. Serum PRL averaged 37 vs 187 and GH 2 vs 4 ng/ml in HST compared with SOC, whereas LH abruptly decreased to undetectable levels after HST compared with a modest 0A4 ng/ml in SOC heifers. The second finding was that parturition and lactation occurred in HST heifers with calf delivery induced to occur at the same time as SOC. Milk production in HST animals was severely limited, and postpartum estrus obliterated compared with SOC. The suckling stimulus sustained milk ejection in HST heifers in spite of diminished PRL and GH secretion. The results suggest that PRL, GH and possibly placental lactogen are luteotropic during pregnancy in cattle.

Role of the Central Nervous System in the Regulation of Pregnancy, Parturition and Lactation in Beef Heifers

Progesterone secretion is crucial for maintaining pregnancy to parturition in mammalian species, and in cattle the corpus luteum is the primary source of this hormone. This study determined the roles of prolactin (PRL), growth hormone (GH) and luteinizing hormone (LH) in the luteotropic process in beef heifers hypophyseal stalk-transected (HST, n = 7) or sham operated on (SOC, n = 9) during midgestation. The main finding was that endogenous PRL and GH maintained progesterone secretion in HST heifers similar to that in SOC throughout pregnancy. Serum PRL averaged 37 vs. 187 and GH 2 vs. 4 ng/ml in HST compared with SOC, whereas LH abruptly decreased to undetectable levels after HST compared with a modest 0.4 ng/ml in SOC heifers. The second finding was that parturition and lactation occurred in HST heifers with calf delivery induced to occur at the same time as SOC. Milk production in HST animals was severely limited and postpartum estrus obliterated compared with SOC. The suckling stimulus sustained milk ejection in HST heifers in spite of diminished PRL and GH secretion. The results suggest that PRL, GH, and possibly placental lactogen are luteotropic during pregnancy in cattle.

Brain Neuropeptides That Control Prolactin Secretion in Cattle

The objective was to test the hypothesis that dopamine regulates prolactin (PRL) secretion by determining acute changes in catecholamine concentrations in hypophyseal portal blood of cattle and their relation to peripheral blood concentration of PRL in hypophyseal stalk-transected (HST) and sham-operated control (SOC). Holstein heifers were subjected to neurosurgery to collect hypophyseal portal blood with a stainless steel cannula designed with a cuff placed under the pituitary stalk and peripheral blood via a jugular vein catheter. PRL plasma concentration was measured by radioimmunoassay, and dopamine and norepinephrine in portal plasma by radioenzymatic assay. During anesthesia before HST or SOC, PRL plasma concentration ranged from 20–40 ng/ml throughout 255 minutes. PRL abruptly increased and remained above 90 ng/ml after HST, compared with a steady decrease to <20 ng/ml in SOC heifers throughout 440 minutes. Within 5 minutes after severing of the hypophyseal stalk, dopamine in portal blood (>8 ng/ml) was significantly increased (P<0.05) compared with peripheral blood (<2 ng/ml). Norepinephrine concentration in portal blood was significantly greater (P<0.05) than in peripheral blood during the first 60 minutes. The sustained high PRL level in peripheral plasma after severing the hypophyseal stalk stimulated hypothalamic dopamine secretion from hypophyseal portal vessels during the prolonged period of blood collection. Norepinephrine concentration in these cattle was greater in hypophyseal portal blood than in peripheral blood, implicating both an important hypothalamic source of the catecholamine as well as an adrenal gland contribution during anesthesia.

Impact of Baseline Renal Function on Tenofovir-containing Antiretroviral Therapy Outcomes in Zambia

Background. Although tenofovir (TDF) use has increased as part of first-line antiretroviral therapy (ART) across sub-Saharan Africa, renal outcomes among patients receiving TDF remain poorly understood. We assessed changes in renal function and mortality in patients starting TDF- or non-TDF-containing ART in Lusaka, Zambia. Methods. We included patients aged ≥16 years who started ART from 2007 onward, with documented baseline weight and serum creatinine. Renal dysfunction was categorized as mild (eGFR 60-89 mL/min), moderate (30-59 mL/min) or severe (<30 mL/min) using the CKD-EPI formula. Differences in eGFR during ART were analyzed using linear mixed-effect models, the odds of developing moderate or severe eGFR decrease with logistic regression and mortality with competing risk regression. Results. We included 62,230 adults, of which 38,716 (62%) initiated a TDF-based regimen. The proportion with moderate or severe renal dysfunction at baseline was lower in the TDF compared to the non-TDF group (1.9% vs. 4.0%). Among patients with no or mild renal dysfunction, those on TDF were more likely to develop moderate (adjusted OR: 3.11; 95%CI: 2.52-3.87) or severe eGFR decrease (adjusted OR: 2.43; 95%CI: 1.80-3.28), although the incidence of such episodes was low. Among patients with moderate or severe renal dysfunction at baseline, renal function improved independently of ART regimen and mortality was similar in both treatment groups. Conclusions. TDF use did not attenuate renal function recovery or increase mortality in patients with renal dysfunction. Further studies are needed to determine the role of routine renal function monitoring before and during ART use in Africa.

Current Resources

Reviews of: Kaplan, L., & Girard, J. L. (1994). Strengthening high-risk families: A handbook for practitioners. New York: Lexington. Reviewed by June Lloyd Schuerman, J.R., Rzepnicki, T. L., & Littell, J. H. (1994). Putting families first: An experiment in family preservation. New York: Aldine de Gruyter. Reviewed by Anthony Maluccio and Kristine Nelson Behavioral Sciences Institute, HOMEBUILDERS Training Division. (1992). Skills for Family and Community Living. Federal Way, WA: Author. Reviewed by Pat Sandau-Beckler

Conceptual Bases of the Planning Process in Family Preservation/Family Support State Plans

Congress and the Department of Health and Human Services (DHHS) intend for the Family Preservation and Support Act of 1993 (P.L. 103-66) to catalyze major reforms in state human services systems. DHHS and numerous other institutions developed conceptual and procedural guidance for the states' planning processes. Review of the planning dimensions of participation and expertise reveals that major emphases on stakeholder participation and technical planning processes obscure the need for expertise in family preservation and family support.

Family Preservation Journal, 1997, Volume 2, Issue 1. (Entire issue)

Entire issue (large pdf file) Articles include: What's Working in Family-Based Services?--or, What's Left to Believe in During a Time of Such Doubt? Roger Friedman The Family Preservation Philosophy and Therapy With Lesbian Clients. Pamela de Santa Parenting Pioneers and Parenting Teams: Strengthening Extended Family Ties in Family Support Programs. Susan Whitelaw Downs Conceptual Bases of the Planning Process in Family Preservation/Family Support State Plans. June Lloyd

Regulation and function of {\it Xparaxis\/} during the development of paraxial mesoderm in {\it Xenopus laevis\/}

Genes of the basic helix-loop-helix transcription factor family have been implicated in many different developmental processes from neurogenesis to myogenesis. The recently cloned bHLH transcription factor, paraxis, has been found to be expressed in the paraxial mesoderm of the mouse suggesting a role for paraxis in the development of this mesodermal subtype which gives rise to the axial muscle, skeleton, and dermis of the embryo. In order to perform in vivo gain of function assays and obtain a better understanding of the possible roles of paraxis in mesodermal and somitic development, we have successfully identified homologues of paraxis in the frog, Xenopus laevis, where the process of mesodermal induction and development is best understood. The two homologues, Xparaxis-a and Xparaxis-b, are conserved with respect to their murine homologue in structure and expression within the embryo. Xparaxis genes are expressed immediately after gastrulation in the paraxial mesoderm of Xenopus embryos and are down regulated in the myotome of the mature somite with continued expression in the undifferentiated dermatome. Overexpression of Xparaxis-b in Xenopus embryos caused defects in the organization and morphology of the somites. This effect was not dependent on DNA binding of Xparaxis but is likely due to its dimerization with other bHLH factors. Co-injections with XE12 did not diminish the effects indicating that the defects were not the result of limiting amounts of XE12. We also demonstrated that Xparaxis does not cause obvious defects in the cell adhesions and movements required for proper mesoderm patterning during gastrulation. The paraxis proteins also lacked the ability to activate transcription as GAL4 fusion proteins in a GAL4 reporter assay, indicating that the genes may function more as modulators of the activity of dimerization partners than as positively acting cell determination factors. In agreement with this, Xparaxis is regulated in response to other pathways of bHLH gene action, in that XE12 can activate Xparaxis-b, in vivo. In addition we show regulation of Xparaxis in response to mMyoD induced myogenesis pathways, again suggesting Xparaxis plays an important role in the patterning and organization of the paraxial mesoderm. ^

A new rechargeable device for deep brain stimulation: a prospective patient satisfaction survey

Background: Deep brain stimulation (DBS) is highly successful in treating Parkinson's disease (PD), dystonia, and essential tremor (ET). Until recently implantable neurostimulators were nonrechargeable, battery-driven devices, with a lifetime of about 3-5 years. This relatively short duration causes problems for patients (e.g. programming and device-use limitations, unpredictable expiration, surgeries to replace depleted batteries). Additionally, these batteries (relatively large with considerable weight) may cause discomfort. To overcome these issues, the first rechargeable DBS device was introduced: smaller, lighter and intended to function for 9 years. Methods: Of 35 patients implanted with the rechargeable device, 21 (including 8 PD, 10 dystonia, 2 ET) were followed before and 3 months after surgery and completed a systematic survey of satisfaction with the rechargeable device. Results: Overall patient satisfaction was high (83.3 ± 18.3). Dystonia patients tended to have lower satisfaction values for fit and comfort of the system than PD patients. Age was significantly negatively correlated with satisfaction regarding process of battery recharging. Conclusions: Dystonia patients (generally high-energy consumption, severe problems at the DBS device end-of-life) are good, reliable candidates for a rechargeable DBS system. In PD, younger patients, without signs of dementia and good technical understanding, might have highest benefit.