High follicle density does not decrease sweat gland density in Huacaya alpacas.

When exposed to high ambient temperatures, mammals lose heat evaporatively by either sweating from glands in the skin or by respiratory panting. Like other camelids, alpacas are thought to evaporate more water by sweating than panting, despite a thick fleece, unlike sheep which mostly pant in response to heat stress. Alpacas were brought to Australia to develop an alternative fibre industry to sheep wool. In Australia, alpacas can be exposed to ambient temperatures higher than in their native South America. As a young industry there is a great deal of variation in the quality and quantity of the fleece produced in the national flock. There is selection pressure towards animals with finer and denser fleeces. Because the fibre from secondary follicles is finer than that from primary follicles, selecting for finer fibres might alter the ratio of primary and secondary follicles. In turn the selection might alter sweat gland density because the sweat glands are associated with the primary follicle. Skin biopsy and fibre samples were obtained from the mid-section of 33 Huacaya alpacas and the skin sections were processed into horizontal sections at the sebaceous gland level. Total, primary, and secondary follicles and the number of sweat gland ducts were quantified. Fibre samples from each alpaca were further analysed for mean fibre diameter. The finer-fibred animals had a higher total follicle density (P<0.001) and more sweat glands (P<0.001) than the thicker-fibred animals. The fibre diameter and total follicle density were negatively correlated (R(2)=0.56, P<0.001). Given that the finer-fibred animals had higher follicle density and more sweat glands than animals with thicker fibres, we conclude that alpacas with high follicle density should not be limited for potential sweating ability.

Rumen-protected methionine supplementation and fibre production in alpacas (Vicugna pacos).

Sulphur-containing amino acids are a crucial requirement for fibre production and may be supplemented in the diet of fibre-producing animals to stimulate fibre growth. The alpaca fibre industry is a developing industry in Australia with high variability in fibre production. To date, there is no evidence whether supplementing the diet of alpacas with sulphur amino acids improves fibre production. We hypothesised that supplementation with the rumen-protected sulphur amino acid, methionine would increase fibre growth in alpacas. Three groups of eight huacaya alpaca wethers were fed daily a maintenance diet supplemented with 0, 2 or 4 g of rumen-protected methionine for 7 weeks. Fibre samples were taken at the beginning and end of the study with a blood sample taken by jugular venipuncture prior to feeding on the first day of each week. Methionine supplementation had no effect on fibre diameter (p = 0.92), fibre length (p = 0.91) or fibre yield (p = 0.33). The change of season over the study affected plasma glucose (p < 0.001), plasma urea nitrogen (p < 0.001) and fibre diameter (p < 0.001). The indifference between groups may be due to the maintenance diet supplying sufficient levels of methionine, the lack of genetic potential of the experimental animals to respond to additional methionine or that the supplemental methionine was not protected in alpacas and deaminated for glucose production.

Pathophysiologic characteristics of hypovolemic shock.

In the late 1800s, while caring for a trauma victim, Warren characterized shock as "a momentary pause in the act of death." A great deal about shock has been discovered since this first description. Dorland's Medical Dictionary defines shock as a condition of profound hemodynamic and metabolic disturbance characterized by failure of the circulatory system to maintain adequate perfusion of vital organs. Shock is now being defined at the cellular level as the inadequate delivery of nutrients to the cells of the body. Because oxygen is the only nutrient that cells cannot store in any appreciable quantity, shock is also equivalent to inadequate oxygen delivery (DO2). Although there are many types of shock, this article concentrates on the pathophysiologic characteristics of hypovolemic shock.

Polymyalgia rheumatica and temporal arthritis.

Polymyalgia rheumatica and temporal arteritis are closely related inflammatory conditions that affect different cellular targets in genetically predisposed persons. Compared with temporal arteritis, polymyalgla rheumatica is much more common, affecting one in 200 persons older than 50 years. Temporal arteritis, however, is more dangerous and can lead to sudden blindness. The diagnosis of polymyalgia rheumatica is based on the presence of a clinical syndrome consisting of fever, nonspecific somatic complaints, pain and stiffness in the shoulder and pelvic girdles, and an elevated erythrocyte sedimentation rate. Temporal arteritis typically presents with many of the same findings as polymyalgia rheumatica, but patients also have headaches and tenderness to palpation over the involved artery. Arterial biopsy usually confirms the diagnosis of temporal arteritis. Early diagnosis and treatment of polymyalgia rheumatica or temporal arteritis can dramatically improve patients' lives and return them to previous functional status. Corticosteroid therapy provides rapid and dramatic improvement of the clinical features of both conditions. Therapy is generally continued for six to 24 months. Throughout treatment, clinical condition is assessed periodically. Patients are instructed to see their physician immediately if symptoms recur or they develop new headache, jaw claudication or visual problems.

Age, gender, and bone lamellae elastic moduli.

To enhance preventative and therapeutic strategies for metabolic bone diseases and bone fragility disorders, we began to explore the physical properties of bone tissue at the cellular level. Proximal femurs were harvested from 27 cadavera (16 male and 11 female) for in vitro measurement of the mechanical properties. We measured the variations in lamellar-level elastic modulus and hardness in human bone as a function of age and gender to identify microstructural properties responsible for age and gender-related reductions in the mechanical integrity. The lateral femoral necks were examined, and age, gender, height, body mass, and body mass index were not found to correlate with lamellar-level elastic modulus or hardness. This result was consistent for osteonal, interstitial, and trabecular tissue. These data suggest that increased bone mass maintenance, known to occur in heavier individuals, is not accompanied by increases in the lamellar-level elastic modulus or hardness. The independence of elastic modulus and hardness from age and gender suggests that age and gender-related decreases in mechanical integrity do not involve alterations in elastic modulus or hardness of the extracellular matrix. Lamellar-level ultimate, fatigue, and fracture toughness properties should also be investigated. Other factors, such as tissue mass and organization, may also contribute to age and gender-related decreases in the mechanical integrity.

Health issues in men: Part II. Common psychosocial disorders.

During screening examinations and, when appropriate, other health-related visits, family physicians should be alert for signs and symptoms of common psychosocial disorders in men. Health issues of concern include alcohol and substance abuse, domestic violence, midlife crisis and depression. Alcohol remains the most abused drug in America. The highest rates of alcohol abuse are in men 25 to 39 years of age, although alcoholism is also a considerable problem after 65 years of age. Disulfiram and the opioid antagonist naltrexone are the two medications currently labeled by the U.S. Food and Drug Administration for the treatment of chronic alcohol dependence. Like alcohol abuse, domestic violence is a sign of psychosocial distress in men. Domestic violence may be a problem in up to 16 percent of marriages. Most men move through the midlife period without difficulty. Major depressive illness occurs in about 1 percent of elderly men, whereas minor depression or subsyndromal depression affects 13 to 27 percent of older men. Selective serotonin reuptake inhibitors have become first-line therapy for depression.

Health issues in men: part I: Common genitourinary disorders.

Common genitourinary health issues that arise in the care of male patients include prostatitis, benign prostatic hyperplasia, urogenital cancers, premature ejaculation and erectile dysfunction. Bacterial infections are responsible for only 5 to 10 percent of prostatitis cases. Benign prostatic hyperplasia is present in 90 percent of men by the age of 85. Common urogenital cancers include prostate cancer, transitional cell carcinoma of the bladder and testicular cancer. Although an estimated 10 percent of men eventually develop prostate cancer, screening for this malignancy is one of the most controversial areas of health prevention. Premature ejaculation occurs in as many as 40 percent of men. Treatment with tricyclic antidepressants, selective serotonin reuptake inhibitors, counseling or behavioral therapy may be helpful. Erectile dysfunction affects up to 30 percent of men between 40 and 70 years of age. Stepped therapy is a useful approach to this common malady. Good treatment results have been obtained with orally administered sildenafil and intraurethrally administered alprostadil.

Heterogeneity of bone lamellar-level elastic moduli.

Advances in our ability to assess fracture risk, predict implant success, and evaluate new therapies for bone metabolic and remodeling disorders depend on our understanding of anatomically specific measures of local tissue mechanical properties near and surrounding bone cells. Using nanoindentation, we have quantified elastic modulus and hardness of human lamellar bone tissue as a function of tissue microstructures and anatomic location. Cortical and trabecular bone specimens were obtained from the femoral neck and diaphysis, distal radius, and fifth lumbar vertebra of ten male subjects (aged 40-85 years). Tissue was tested under moist conditions at room temperature to a maximum depth of 500 nm with a loading rate of 10 nm/sec. Diaphyseal tissue was found to have greater elastic modulus and hardness than metaphyseal tissues for all microstructures, whereas interstitial elastic modulus and hardness did not differ significantly between metaphyses. Trabecular bone varied across locations, with the femoral neck having greater lamellar-level elastic modulus and hardness than the distal radius, which had greater properties than the fifth lumbar vertebra. Osteonal, interstitial, and primary lamellar tissues of compact bone had greater elastic moduli and hardnesses than trabecular bone when comparing within an anatomic location. Only femoral neck interstitial tissue had a greater elastic modulus than its osteonal counterpart, which suggests that microstructural distinctions can vary with anatomical location and may reflect differences in the average tissue age of cortical bone or mineral and collagen organization.

Effects of prolactin on expression of Fos-related antigens in tyrosine hydroxylase-immunoreactive neurons in subdivisions of the arcuate nucleus.

Dual immunohistochemistry was employed to determine the effects of prolactin on expression of Fos and its related antigens (FRA) in tuberoinfundibular dopamine (TIDA) neurons located in the dorsomedial (DM) and ventrolateral (VL) subdivisions of the arcuate nucleus (ARC) in the male rat. Systemic administration of the DA receptor antagonist haloperidol caused a sustained (up to 12 h) increase in plasma prolactin concentrations that was accompanied by a transient increase (at 3 h) in the percentage of tyrosine hydroxylase (TH)-immunoreactive (IR) neurons containing FRA-IR nuclei in the DM-ARC. In contrast, haloperidol caused a prolonged (1. 5 to 12 h) decrease in the percentage of TH-IR neurons with FRA-IR nuclei in the VL-ARC. Haloperidol had no effect, however, on the overall number of TH-IR neurons in either of these regions. Co-administration of prolactin antisera (PRL-AB) blocked haloperidol-induced increases in both plasma prolactin concentrations and the percentage of TH-IR neurons expressing FRA in the DM-ARC, but had no effect on haloperidol-induced inhibition of FRA expression in TH-IR neurons in the VL-ARC. Intracerebroventricular (i.c.v.) administration of prolactin also increased the percentage of TH-IR neurons containing FRA-IR nuclei in the DM-ARC, but this effect was of longer duration (up to 6 h) than that of haloperidol in all but the most caudal portion of the DM-ARC. In the VL-ARC, prolactin caused a transient increase (at 1.5 h) in the percentage of TH-IR containing FRA-IR nuclei. These results demonstrate that prolactin regulates immediate early gene expression in TIDA neurons in male rats, and reveal that there are temporal differences in the responsiveness of discrete subpopulations of these neurons to prolactin. Prolactin causes a short-lived increase in FRA expression in TIDA neurons in the VL-ARC which is followed by a more prolonged activation of FRA expression in TIDA neurons in the DM-ARC.

Prolactin regulation of tuberoinfundibular dopaminergic neurons: immunoneutralization studies.

The purpose of this study was to determine the effects of acute hypoprolactinemia on tuberoinfundibular dopamine (DA) neurons using a rabbit anti-rat prolactin antiserum (PRL-AB) to immunoneutralize circulating prolactin under basal conditions and at various times after haloperidol-induced hyperprolactinemia. The specificity of PRL-AB for prolactin was determined by examining the ability of unlabelled hormone to displace binding of 125I-labelled prolactin to PRL-AB. Tuberoinfundibular DA neuronal activity was estimated by measuring the concentrations of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence which contains terminals of these neurons. Systemic (i.v.) administration of 200 microl of PRL-AB decreased plasma prolactin concentrations below detectable levels for at least 4 h, and this was accompanied by a pronounced decrease in DOPAC concentrations in the median eminence of females, but not males. Central (i.c.v.) administration of 2 microl PRL-AB diluted up to 1:100 mimicked the inhibitory effect of systemic administration of PRL-AB on median eminence DOPAC concentrations suggesting that the tonic stimulatory effect of prolactin on the basal activity of tuberoinfundibular DA neurons in females occurs via a central site of action. In male rats, blockade of anterior pituitary DA receptors with haloperidol (1 mg/kg; s.c.) caused an prompt (by 1 h) increase in plasma prolactin concentrations which was maintained for at least 12 h. Haloperidol-induced hyperprolactinemia also caused a delayed (at 6 and 12 h) increase in median eminence DOPAC concentrations in these animals which was blocked by PRL-AB. Exposure of rats to initial priming periods of endogenous hyperprolactinemia of up to 6 h duration (followed by 6 h or more of PRL-AB-induced hypoprolactinemia) failed to alter median eminence DOPAC concentrations unless prolactin exposure was reinstated by an i.c.v. injection of prolactin. These results confirm that prolactin mediates the stimulatory effects of haloperidol on tuberoinfundibular DA neurons, and reveal that delayed induced activation of these neurons by prolactin is dependent upon a priming period of sustained hyperprolactinemia longer than 3 h for initiation and maintenance of this response.

Elastic modulus and hardness of cortical and trabecular bone lamellae measured by nanoindentation in the human femur.

The mechanical properties of bone tissue are determined by composition as well as structural, microstructural and nanostructural organization. The aim of this study was to quantify the elastic properties of bone at the lamellar level and compare these properties among osteonal, interstitial and trabecular microstructures from the diaphysis and the neck of the human femur. A nanoindentation technique with a custom irrigation system was used for simultaneously measuring force and displacement of a diamond tip pressed 500 nm into the moist bone tissue. An isotropic elastic modulus was calculated from the unloading curve with an assumed Poisson ratio of 0.3, while hardness was defined as the maximal force divided by the corresponding contact area. The elastic moduli ranged from 6.9 +/- 4.3 GPa in trabecular tissue from the femoral neck of a 74 yr old female up to 25.0 +/- 4.3 GPa in interstitial tissue from the diaphyseal cortex of a 69 yr old female. The mean elastic modulus was found to be significantly influenced by the type of lamella (p < 10(-6)) and by donor (p < 10(-6)). The interaction between the type of lamella and the donor was also highly significant (p < 10(-6)). Hardness followed a similar distribution as elastic modulus among types of lamellae and donor, but with lower statistical contrast. It is concluded that the nanostructure of bone tissue must differ substantially among lamellar types, anatomical sites and individuals and suggests that tissue heterogeneity is of potential importance in bone fragility and adaptation.

Opposing roles for dopamine D1 and D2 receptors in the regulation of hypothalamic tuberoinfundibular dopamine neurons.

The purpose of the present study was to characterize pharmacologically dopamine D1 receptor-mediated inhibition of tuberoinfundibular dopamine neurons in males rats, and to determine if inhibitory dopamine D1 receptors oppose stimulatory dopamine D2 receptors and account for the inability of mixed dopamine receptor agonists to alter the activity of these neurons. Tuberoinfundibular dopamine neuronal activity was estimated by measuring the concentrations of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the median eminence, the region of the hypothalamus containing terminals of these neurons. Administration of the dopamine D1 receptor agonist (+/-)-1 phenyl-2,3,4,5-tetrahydro-(1 H)-3-benzazepine-7,8-diol (SKF38393) decreased median eminence DOPAC and increased plasma prolactin concentrations, whereas administration of the dopamine D1 receptor antagonist ((-)-trans,6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo[d]naphtho-[2,1 b]azepine (SCH39166) increased median eminence DOPAC concentrations but had not effect on plasma prolactin. The inhibitory effect of SKF38393 on median eminence DOPAC concentrations was blocked by SCH39166. These results demonstrate that acute activation of dopamine D1 receptors inhibits the activity of tuberoinfundibular dopamine neurons and thereby increases prolactin secretion, and that under basal conditions dopamine D1 receptor-mediated inhibition of tuberoinfundibular dopamine neurons is tonically active. Administration of the dopamine D2 receptor agonist (5aR-trans)-5,5a,6,7,8,9,9a,10-octahydro-6-propyl-pyridol[2, 3-g]quinazolin-2-amine (quinelorane) increased median eminence DOPAC concentrations, and SKF38393 caused a dose-dependent reversal of this effect. Administration of the mixed dopamine D1/D2 receptor agonist R(-)-10,11-dihydroxy-apomorphine (apomorphine) had no effect per se, but blocked quinelorane-induced increases in DOPAC concentrations in the median eminence. These results reveal that concurrent activation of dopamine D1 and D2 receptors nullifies the actions of each of these receptors on tuberoinfundibular dopamine neurons, which likely accounts for the lack of an acute effect of mixed dopamine D1/D2 receptor agonists on these hypothalamic dopamine neurons.

Contribution of dopamine neurons in the medial zona incerta to the innervation of the central nucleus of the amygdala, horizontal diagonal band of Broca and hypothalamic paraventricular nucleus.

Results of previous studies suggested that incertohypothalamic dopamine (IHDA) neurons located in the medial zona incerta (MZI) project to the central nucleus of the amygdala (cAMY), horizontal diagonal band of Broca (HDB), and paraventricular nucleus (PVN). The overall goal of the present study was to determine the relative contribution of IHDA neurons to the DA innervation of these brain regions. A combined fluorescent and in situ hybridization histochemical procedure was employed to localize the retrograde tracer fluoro-gold (FG) in cells expressing tyrosine hydroxylase (TH) mRNA in the MZI following its iontophoretic injection into either the cAMY, HDB or PVN. For comparison, the numbers of dual labeled FG/TH mRNA neurons in the midbrain were also determined. One week after unilateral injection of FG into the cAMY, cells containing FG+TH mRNA were found in the ipsilateral MZI, substantia nigra zona compacta (SNC) and ventral tegmental area (VTA). The total numbers of cells labeled with FG varied with the size of the injection site, but the ratio of dual labeling in the MZI to that of the SNC-VTA remained constant across animals at approximately 1:6. FG injections into the HDB resulted in a ratio of dual labeled cells in the ipsilateral MZI and VTA of approximately 1:2, but no dual labeled cells were found in the SNC. Dual labeled cells were only found in the ipsilateral MZI in animals receiving FG injections in the PVN. Thus, DA terminals in the PVN originate exclusively from IHDA neurons in the MZI, whereas these neurons provide only a portion of the DA innervation of the cAMY and HDB. The similar distribution of dual labeled cells in the MZI following FG injections into the cAMY, HDB and PVN suggests that perikarya of IHDA neurons projecting to these regions are not organized into distinct groups.

Pharmacological evidence that neurotensin mediates prolactin-induced activation of tuberoinfundibular dopamine neurons.

The purpose of this study was to investigate the role of neurotensin (NT) receptors in mediating the stimulatory effects of prolactin on the activity of tuberoinfundibular dopamine (TIDA) neurons in male and female rats. TIDA neuronal activity was estimated by measuring concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in terminals of these neurons in the median eminence (ME). Haloperidol activates TIDA neurons indirectly by blocking D2 receptors on pituitary lactotropes, thereby increasing secretion of prolactin. Twelve hours after administration of haloperidol (1 mg/kg, s.c.), DOPAC concentrations in the ME were increased. Blockade of NT receptors with the selective antagonist SR-48692 had no effect per se on basal DOPAC concentrations in the ME but produced a dose-related (10-1,000 microg/kg, i.p.; 1 h) reversal of haloperidol-induced increases in ME DOPAC concentrations. In contrast, SR-48692 had no effect on either basal or haloperidol-induced increases in plasma prolactin. SR-48692 also blocked the stimulatory effects of prolactin (10 microg/rat, i.c.v.; 12 h) on ME DOPAC concentrations. SR-48692 was equally effective in blocking the stimulatory effects of haloperidol and prolactin on TIDA neurons in male and female rats. These results suggest that NT mediates the induced stimulatory effect of hyperprolactinemia on the activity of TIDA neurons in both males and females, whereas the tonic regulation of these neurons by prolactin in females occurs via an NT-independent mechanism.

Mechanical properties of human trabecular bone lamellae quantified by nanoindentation.

Improved preventive and therapeutic strategies for skeletal diseases such as osteoporosis rely on a better understanding of the mechanical properties of trabecular bone and their influence on cell mediated adaptation processes. The mechanical properties of trabecular bone are determined by composition as well as structural (trabecular architecture), microstructural (trabecular packets) and nanostructural (lamellae) organization. Density is the major predictor of the mechanical properties of trabecular structures and has been extended to the concept of fabric to include architectural anisotropy and improve even further the power of prediction. Recent advances in QCT and MRI technologies allow for precise assessment of 3D trabecular architecture and the mechanical consequences of structural changes can be increasingly well quantified by the means of computational methods. While single trabeculae have been tested using various techniques with contrasting results, little is known about the intrinsic mechanical properties of trabecular bone lamellae on which these computational methods rely. For instance, water and mineral content have a significant effect on the elastic, viscous, yield and postyield properties of bone tissue. In addition, collagen fiber orientation affects the mechanics of single remodeling units. Variations in composition and organization determined by age, accumulated damage or disease may therefore reduce the mechanical integrity of trabecular bone and deserve more attention. The aim of this work was to utilize a nanoindentation technique to quantify elastic modulus and hardness of human trabecular bone lamellae.

Effects of selective activation of dopamine D2 and D3 receptors on prolactin secretion and the activity of tuberoinfundibular dopamine neurons.

Dopamine agonists with activity at both dopamine D2 and D3 receptor subtypes stimulate tuberoinfundibular dopamine neurons and inhibit prolactin secretion from the anterior pituitary. The purpose of the present study was to identify the dopamine receptor subtypes mediating these effects using recently developed selective agonists for dopamine D2 (PNU-95,666) and D3 (PD128907) receptors. The activity of tuberoinfundibular dopamine neurons was estimated by measuring either the synthesis (accumulation of 3,4-dihydroxyphenyl-alanine [DOPA] following inhibition of decarboxylase activity) or metabolism (3,4-dihydroxyphenylacetic acid [DOPAC] concentrations) of dopamine in the median eminence, the region of the hypothalamus containing axon terminals of these neurons. In one experiment, the activity of mesolimbic dopamine neurons was also determined by measuring DOPA accumulation in terminals of these neurons in the nucleus accumbens. Activation of dopamine D2 receptors with PNU-95,666 caused dose- and time-related increases in DOPAC concentrations in median eminence which were temporally correlated with decreases in plasma prolactin concentrations. Activation of dopamine D3 receptors with PD128907 decreased DOPA concentrations in the nucleus accumbens, but had no effect on concentrations of DOPAC or DOPA in the median eminence or prolactin in plasma. These results reveal that tuberoinfundibular dopamine neurons are regulated by dopamine D2 rather than D3 receptors, and suggest that the ability of mixed dopamine D2/D3 receptor agonists to increase the activity of these neurons is mediated by an action at dopamine D2 receptors. Furthermore, these results confirm that tuberoinfundibular dopamine neurons are not regulated by inhibitory dopamine D2 or D3 autoreceptors.

Role of gonadal steroids in determining sexual differences in expression of Fos-related antigens in tyrosine hydroxylase-immunoreactive neurons in subdivisions of the hypothalamic arcuate nucleus.

Dual immunohistochemistry was employed to examine the role of gonadal steroids in determining sexual differences in the expression of Fos and its related antigens (FRA) in tuberoinfundibular dopaminergic (TIDA) neurons located in the dorsomedial (DM-) and ventrolateral (VL-) subdivisions of the arcuate nucleus (ARC). In the DM-ARC, there was no sexual difference in the number of tyrosine hydroxylase (TH)-immunoreactive (-IR) perikarya, but the number of these containing FRA-IR was greater in females than in males in all but the most caudal region. In the VL-ARC, there were more TH-IR perikarya in males than in females, but there was no sexual difference in the numbers of those containing FRA-IR throughout the entire rostrocaudal extent of this nucleus. Ovariectomy decreased the number of TH-IR perikarya containing FRA-IR in the DM-ARC, but not in the VL-ARC, whereas orchidectomy increased the number of TH-IR perikayra containing FRA-IR in both the DM-ARC and VL-ARC. These gonadectomy-induced effects were reversed by estrogen and testosterone, respectively. These results reveal gonadal steroid-dependent sexual differences in the regulation of immediate early gene expression in anatomically discrete subpopulations of TIDA neurons. In females, estrogen stimulates FRA expression in TIDA neurons in the DM-ARC, whereas in males, testosterone inhibits FRA expression in TIDA neurons in both the DM-ARC and the VL-ARC.

Dopamine receptor-mediated regulation of expression of Fos and its related antigens (FRA) in somatostatin neurons in the hypothalamic periventricular nucleus.

Somatostatin (SS)-containing perikarya located within the hypothalamic periventricular nucleus (PeVN) comprise a heterogenous population of neurons with both local intrahypothalamic and distant extrahypothalamic axonal projection sites. The close proximity of SS perikarya and their dendrites to dopaminergic (DA) neuronal processes in the PeVN suggests that these peptidergic neurons may be regulated by DA receptor-mediated mechanisms. To test this, the effects of the D1 agonist SKF 38393 and D2/3 agonist quinelorane were examined on expression of the immediate early gene products Fos and its related antigens (FRA) in SS-immunoreactive (IR) neurons in the PeVN. SS-IR neurons were located in the most medial portion of the PeVN bordered medially by the third ventricle and laterally by tyrosine hydroxylase (TH)-IR neurons. In control rats, 10-15% of all SS-IR neurons contained FRA-IR. Activation of D1 receptors with SKF 38393 had no effect on either the total number of SS-IR neurons or the number of SS-IR neurons containing FRA-IR. In contrast, activation of D2/3 receptors with quinelorane decreased the number of SS-IR neurons containing FRA-IR, without affecting the total number of SS-IR neurons. The D2/3 antagonist raclopride had no effect per se, but prevented the quinelorane-induced decrease in the number of SS neurons expressing FRA-IR. These results reveal that activation of D2/3 (but not D1) receptors inhibits expression of the immediate early gene products FRA in SS-containing neurons in the PeVN, but expression of FRA in SS neurons is not tonically inhibited by dopamine acting on D2/3 receptors.

Experimental analysis of fluid mechanical energy losses in aortic valve stenosis: importance of pressure recovery.

Current methods for assessing the severity of aortic stenosis depend primarily on measures of maximum systolic pressure drop at the aortic valve orifice and related calculations such as valve area. It is becoming increasingly obvious, however, that the impact of the obstruction on the left ventricle is equally important in assessing its severity and could potentially be influenced by geometric factors of the valve, causing variable degrees of downstream pressure recovery. The goal of this study was to develop a method for measuring fluid mechanical energy losses in aortic stenosis that could then be directly related to the hemodynamic load placed on the left ventricle. A control volume form of conservation of energy was theoretically analyzed and modified for application to aortic valve stenosis measurements. In vitro physiological pulsatile flow experiments were conducted with different types of aortic stenosis models, including a venturi meter, a nozzle, and 21-mm Medtronic-Hall tilting disc and St. Jude bileaflet mechanical valves. The energy loss created by each model was measured for a wide range of experimental conditions, simulating physiological variation. In all cases, there was more energy lost for the nozzle (mean = 0.27 J) than for any other model for a given stroke volume. The two prosthetic valves generated approximately the same energy losses (mean = 0.18 J), which were not statistically different, whereas the venturi meter had the lowest energy loss for all conditions (mean = 0.037 J). Energy loss correlated poorly with orifice pressure drop (r2 = 0.34) but correlated well with recovered pressure drop (r2 = 0.94). However, when the valves were considered separately, orifice and recovered pressure drop were both strongly correlated with energy loss (r2 = 0.99, 0.96). The results show that recovered pressure drop, not orifice pressure drop, is directly related to the energy loss that determines pump work and therefore is a more accurate measure of the hemodynamic significance of aortic stenosis.