Effects of the estrous cycle stage on the prolactin secretory response to dopamine in vitro

Dopamine (DA) will both stimulate and inhibit prolactin (PRL) secretion from the anterior pituitary gland in vitro and in vivo. The present study was designed to determine if there are selected times during the estrous cycle of the rat when one function is favored over the other. Anterior pituitary glands collected on diestrus-1 (D1), diestrus-2 (D2), the morning of proestrus (Pro-AM), the afternoon of proestrus (Pro-PM), and estrus (E) were enzymatically dissociated and placed in monolayer culture. On the fourth day in culture, cells were challenged for 10, 20, 30, 60, 120, 180, or 240 min with media alone or media containing either 100 pM or 1 μM DA. The concentration of PRL in the media was determined by radioimmunoassay. Regression analysis revealed that in the absence of DA, PRL secretion from cultured cells differed significantly depending on the stage of the estrous cycle during which they were obtained. Cells obtained during the morning of diestrus-2 secreted PRL at the greatest rate compared to other stages of the cycle. When all stages were compared, the rates of PRL secretion were: D2>E>D1>Pro-AM>Pro-PM (each significantly different from the others,P<0.01). By 20–30 min of exposure to 100 pM DA, the rate of PRL secretion from cells obtained during each stage of the cycle was significantly enhanced. This enhanced secretion persisted in cells obtained during D2 and Pro-PM but was short-lived in cells obtained during other stages. No inhibition of PRL secretion was induced by this dose of DA. PRL secretion was inhibited when treated with 1 μM DA in cells obtained at all stages of the estrous cycle. Inhibition was more prolonged in cells obtained on D1, D2, and Pro-AM. DA was least effective as an inhibitor of PRL secretion in cells obtained during Pro-PM and E. Prior to inhibiting PRL secretion in cells obtained during Pro-PM, 1 μM DA rapidly stimulated PRL secretion. This effect persisted for 60 min. These data suggest that in the absence of DA, the dynamics of PRL secretion from anterior pituitary cells in vitro differ depending on the stage of the estrous cycle during which the cells were obtained. Moreover, the in vivo environment of the cell determines the direction and magnitude of the PRL-secretory response to DA.     

The safety and pharmacokinetics of recombinant soluble CD4 (rCD4) in subjects with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase 1 study

STUDY OBJECTIVE: To evaluate the safety and pharmacokinetics of recombinant, soluble human CD4 (rCD4) in subjects with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. The protein rCD4 binds to envelope protein, gp120, of the human immunodeficiency virus (HIV) and blocks HIV infection of CD4 lymphocytes in vitro. DESIGN: Phase 1 trial with dose escalation. SETTING: Two university-affiliated hospital clinics. SUBJECTS: Of 42 subjects enrolled, 29 had AIDS and 13 had AIDS-related complex. INTERVENTIONS: The rCD4 was administered by rapid intravenous infusion on day 1, followed by a 3-day washout, then once a day for 10 days, followed by a 7-day washout, and then three times a week for 8 weeks. Doses of 1, 10, 30, 100, and 300 micrograms/kg body weight per day of rCD4 were administered intravenously to 6 subjects at each dose level. Twelve additional patients received 300 micrograms/kg.d of rCD4: 6 by intramuscular and 6 by subcutaneous injection. All subjects were monitored for toxicity. Immunologic and virologic variables were also monitored. MEASUREMENTS and MAIN RESULTS: Administration of rCD4 was not associated with important toxicity as determined by clinical monitoring or by serum chemistry, hematologic, or immunologic variables. No subjects required dose reduction or discontinuation of therapy due to rCD4-related toxicity. No consistent or sustained changes in CD4 lymphocyte populations or HIV antigen levels were observed. The volume of distribution of rCD4 was small, and clearance remained constant over the dose range studied. The bioavailability of intramuscular injection and subcutaneous injection was 51% and 45%, respectively. CONCLUSIONS: At the dose levels used in this study, rCD4 appears safe and well tolerated. Serum concentrations of rCD4 were achieved that were comparable to concentrations shown to have antiviral activity in vitro. Further studies are indicated to determine whether rCD4 or related molecules will be useful in treating HIV infection.     

Toward clinical care guidelines for supporting rehabilitative vaginal dilator use with women recovering from cervical cancer

Purpose

Building upon the findings of a recent qualitative investigation of women’s experiences with rehabilitative vaginal dilator use, the primary goal of this article is to outline a set of preliminary clinical care recommendations that health care professionals may draw upon in addressing women’s unique experiences with vaginal dilator use including their multifaceted struggles with the procedure, possibly enhancing adherence to this practice.

Methods

Ten women participated in in-depth interviews regarding their experiences with using the dilator as prescribed by their health care providers. Following the analysis of these interviews, members of the interdisciplinary research team met to review and discuss the development of clinical care recommendations stemming from these findings.

Results

Eight care recommendations aimed at addressing the concerns expressed by the women interviewed and at improving women’s overall experiences with rehabilitative dilator use emerged: (1) introduce the dilator in a light and straightforward manner; (2) enhance dilator accessibility; (3) introduce the vaginal dilator early on in treatment; (4) emphasize health maintenance over intercourse as a benefit of dilator use; (5) explore and acknowledge women’s values and views of sexuality; (6) increase awareness and sensitivity to emotional reactions; (7) enhance psychoeducational resources for supporting vaginal dilator use; and (8) ensure consistent institutional practice when introducing the dilator.

Conclusion

The clinical care recommendations proposed here reflect the various challenges women may encounter when using the vaginal dilator—which vary from practical to, for some, profoundly emotional—and are designed to better position health care providers to help women navigate these challenges.     

Possible association between passive smoking and lower exhaled nitric oxide in asthmatic children

In adults, both active and passive smoking reduce levels of exhaled nitric oxide (eNO); however, to date, passive exposure to environmental tobacco smoke (ETS) has not been shown to affect eNO in children. The authors recruited 174 asthmatic children (96 male, 78 female) and 79 nonasthmatic controls (46 male, 33 female) from a group of children aged 5 to 14 yr who attended a children's hospital for an outpatient visit or elective surgery. Each subject's exposure to ETS was ascertained by questionnaire, and their eNO levels were measured. Asthmatic children had higher eNO levels (ppb) than nonasthmatic children (p = 0.04), and asthmatic children exposed to ETS had significantly lower eNO levels than unexposed children (p = 0.005). Exposure to ETS did not alter eNO levels in nonasthmatic children (p = 0.4). Results of the study suggest that ETS exposure is associated with lower eNO levels among childhood asthmatics. Consequently, ETS exposure may need to be considered when physicians interpret eNO levels in asthmatic children. Further study of the effects of ETS on eNO levels is recommended.     

The hemodynamic effects of internal carotid artery stenosis and occlusion

The purpose of this study was to determine in subhuman primates whether hemodynamic mechanisms (as compared with embolic mechanisms) contribute to cerebral ischemia following carotid artery occlusion or stenosis. Following carotid artery occlusion there was loss of cerebral autoregulation: cerebral blood flow (CBF) measured with the xenon-133 technique became passively dependent upon the mean arterial blood pressure (MABP) over an MABP range of 30 to 110 mm Hg. By contrast, autoregulation was preserved in normal animals and in animals with a 90% carotid artery stenosis. Regional CBF was measured with carbon-14-labeled iodoantipyrine autoradiography in normotensive baboons, in hypotensive animals, and in hypotensive animals with carotid artery occlusion or stenosis. With carotid artery occlusion and hypotension, reduced levels of local CBF were seen ipsilaterally in the boundary zones between the anterior and middle cerebral arteries with 35% of the area of an anterior section through the hemisphere displaying a CBF value of less than 20 ml/100 gm/min. Comparable values with hypotension were 21% with carotid artery stenosis, 20% with no proximal vascular lesion, and 1% in normotensive animals. These areas of reduced CBF corresponded with areas of boundary-zone ischemia seen with light microscopy. The study suggests that while hemodynamic ischemia develops with carotid artery occlusion, it does not occur with even a 90% carotid artery stenosis or in normal animals.     

Corpus callosum: Demasculinization via perinatal anti-androgen

The male rat's corpus callosum is significantly larger than the female's. This dimorphism depends in part on the early presence of testosterone, since postnatal administration of testosterone to female pups enlarges their callosa in adulthood to the size of males. However, castrating males on day 1 is ineffective in reducing (demasculinizing) the size of their callosa as adults. We then addressed the question as to whether testosterone acts prior to day 1 to enlarge the callosa of males. To investigate this hypothesis pregnant rats were administered a non-steroidal androgen blocker, flutamide, during the last 5 days of pregnancy, while controls received vehicle only. Male pups from flutamide litters were castrated on day 3 to prevent postnatal recovery following clearance of flutamide, while others received sham surgery. Callosal sex differences were found between males and females of control litters, but not between males and females from flutamide litters. The absence of sex effects among flutamide litters was a consequence of small callosal size in flutamide-castrated males as compared to control males. We concluded that the prenatal production of testosterone in the male rat pup contributes to sexual dimorphism in the callosa of adult rats.     

Nucleotide sequence and genomic organization of feline immunodeficiency virus.

An infectious molecular clone of the Petaluma strain of feline immunodeficiency virus (FIV) was isolated from a recombinant bacteriophage library containing genomic DNA prepared from FIV-infected Crandall feline kidney (CRFK) cells. The integrated provirus has a total length of 9472 base pairs. Three long open reading frames corresponding to GAG, POL, and ENV gene coding frames are evident. In addition, an open reading frame overlaps the 3' end of POL, in the region that encodes viral infectivity factor in the primate viruses. Several short open reading frames are present in the intergenic region between POL and ENV and within ENV, which may serve as exons for production of TAT and REV equivalents in FIV. Alignment of the predicted amino acid sequences of the FIV proteins with those of other lentiviruses indicates that FIV did not arise recently from any other characterized lentivirus.     

Transesophageal echocardiography interpretation: a comparative analysis between cardiac anesthesiologists and primary echocardiographers.

Diagnostic interpretation of intraoperative transesophageal echocardiography (TEE) examinations may vary, particularly when the echocardiographer is also the anesthesiologist. We therefore evaluated the concordance of TEE interpretation as part of a process of continuous quality improvement (CQI). Ten cardiac anesthesiologists participating in a CQI program conducted 154 comprehensive TEE examinations, each consisting of 16 major fields describing cardiac anatomy and function. These examinations were subsequently interpreted off-line by two primary echocardiographers (a radiologist and a cardiologist). Agreement was assessed using the kappa coefficient and percent agreement. Overall kappa and percent agreement were 0.58 and 83% for anesthesiologists versus radiologist, 0.57 and 80% for anesthesiologists versus cardiologist, and 0.60 and 82% for radiologist versus cardiologist. Anesthesiologists with longer than 5 yr of TEE experience had higher levels of agreement with the radiologist when assessing the aorta, right atrium, pulmonary vein flow, transmitral flow, and fractional area change. Cardiac anesthesiologists supported by a CQI program interpret TEE examinations at a level comparable with physicians whose primary practice is echocardiography. Thus, the anesthesiologist and the intraoperative echocardiographer need not be mutually exclusive. IMPLICATIONS: Interpretation of intraoperative transesophageal echocardiograms can be reliably performed by cardiac anesthesiologists.     

Analysis of influenza A virus nucleoproteins for the assessment of molecular genetic mechanisms leading to new phylogenetic virus lineages

Summary The nucleoprotein (NP) gene of influenza A viruses is decisive for separating two large individually evolving reservoirs in birds and humans. A phylogenetic analysis of the NP gene revealed that all mammalian influenza viruses originated — directly or indirectly — from an avian ancestor. The stable introduction of an avian influenza A virus into a mammalian species seems to be a relatively rare event, the latest one occurred in 1979 when such an avian virus was introduced into pigs in Northern Europe which gave rise to a new lineage. At least two concomitant events are required for such a new and stable introduction: (1) The new species has to become infected, and (2) a mutation in the polymerase complex has to establish a labile variant, which is prone to provide a large number of different variants, from which some can adapt rapidly to the new host (or to any unusual environments). Since such mutator mutations might be advantageous only during stress periods, variants with a less error prone polymerase might emerge again after adaptation. Examples for such fluctuations in terms of mutational and evolutionary rates are discussed in this brief review.