Metabolic variables and plasma leptin concentrations in dairy cows exhibiting reproductive cycle abnormalities identified through milk progesterone monitoring during the post partum period.

We have used milk progesterone analysis to monitor reproductive function in lactating dairy cows and have then related this reproductive function to a variety of metabolic variables. Monitoring of cows (n = 41) during the period of onset of luteal function (first milk progesterone reading>5 ng/ml) revealed that delayed onset was associated with increased milk yield and greater loss of body weight and body condition but was not related to plasma metabolite or leptin concentrations. Further monitoring of reproductive function in these 41 cows and an additional 33 cows (total n = 74) during the mating period (from weeks 6 to 14 post partum) identified reproductive cycle abnormalities in 29 (39.2% of animals). The occurrence of cycle abnormalities was associated with increased milk yield (P < 0.05), elevated plasma beta hydroxybutyrate (P < 0.05) and reduced plasma leptin (P < 0.01) concentrations as well as a lower (P < 0.05) rate of gain of body weight and condition score but was not associated with plasma urea or glucose concentrations. Furthermore, cows exhibiting cycle abnormalities had a longer (P < 0.01) interval to first service and a smaller percentage had conceived by 100 days post partum (34.5% versus 66.7%; P < 0.01). These results provide further evidence that impaired reproductive function during the post partum period in dairy cows is caused by a poor energy status and not elevated urea concentrations. Reduced plasma leptin concentrations in animals suffering reproductive dysfunction further supports this view.

Characterisation of long term cat placental explant cultures: uptake of taurine by system beta.

Dietary taurine is essential for cats and deficiency during pregnancy may lead to abortion, growth restriction or impaired neurological function of kittens. We previously described Na(+)- and Cl(-)-dependent taurine transport by system beta in fragments of freshly isolated cat placenta [Champion EE, Bailey SJ, Glazier JD, Jones CJP, Mann SJ, Rawlings JM, et al. Taurine uptake into cat placental tissue fragments. Placenta 2001;22:A.42]. Here we evaluate long term culture of cat placental explants as a model for the future study of chronic nutrient regulation of amino acid transport in this species. The cat placental explants displayed (i) Na(+)-dependent [(3)H]taurine uptake and (ii) taurine transporter protein on day 7 of culture, as observed in fresh cat placental fragments. The explants had preserved the ability to secrete PGF(2alpha) hormone until day 11 of culture and remained morphologically largely intact until day 7 of culture. This model of placental explant culture will provide an important in vitro method for the study of chronic regulation of amino acid transport in the cat.

System beta and system A amino acid transporters in the feline endotheliochorial placenta.

There is no knowledge of the transport mechanisms by which solutes cross the cat placenta or any other endotheliochorial placenta. Here, we investigated whether the amino acid transport systems beta and A are present in the cat placenta using a placental fragment uptake technique. Data were compared with studies in the human placenta, in which the presence of these two transport systems has been well established. A time course of [(3)H]taurine (substrate for system beta) and [(14)C]MeAIB (nonmetabolizable substrate for system A) uptake was determined in the term cat and human placental fragments in the presence and absence (choline substituted) of Na(+), and further studies were carried out over 15 min. Taurine uptake into both cat and human placenta fragments was found to be Na(+) and Cl(-) dependent, and Na(+)-dependent taurine uptake was blocked by excess beta-alanine. MeAIB uptake was found to be Na(+) dependent, and Na(+)-dependent MeAIB uptake was blocked by excess MeAIB or glycine. Western blotting and immunohistochemistry performed on cat and human placenta showed expression of TAUT and ATA2 (SNAT2), proteins associated with system beta and system A activity, respectively. This study therefore provides the first evidence of the presence of amino acid transport systems beta and A in the cat placenta.

Localization of alkaline phosphatase and Ca2+-ATPase in the cat placenta.

We localized alkaline phosphatase and plasma membrane calcium-ATPase (PMCA) in the cat placental syncytiotrophoblast to address their polarized distribution and their potential as markers for specific plasma membrane purification. We used enzyme- (alkaline phosphatase) and immuno- (PMCA) histochemistry and, for alkaline phosphatase, compared data to observations on the human placenta. Alkaline phosphatase activity in the cat was localized to the decidual cell membranes, to within the associated interstitial space and on the subjacent apical (maternal facing) plasma membrane of the syncytiotrophoblast. Occasional maternal capillaries were positive on their basal surface and there was focal staining within the syncytiotrophoblast. This widespread distribution is less specific than in the human placenta where alkaline phosphatase was restricted to the apical and basal plasma syncytiotrophoblast membranes, with much greater density on the apical membrane. Expression of PMCA in the cat was restricted to the basal membrane of the syncytiotrophoblast only. This specific localization of PMCA is identical to the human placenta and all other species in which its placental localization has been studied. We conclude that the plasma membranes of the cat syncytiotrophoblast show a broadly similar functional polarization to the human and that PMCA would prove a useful marker in isolation of the cat syncytiotrophoblast basal plasma membrane.

Production of recombinant ovine interferon tau using a Bombyx mori nuclear polyhedrosis baculovirus expression system.

Ovine interferon tau (oIFN-tau) is an embryonic protein of critical importance in the establishment of pregnancy in the sheep. We have produced recombinant (r) oIFN-tau using a baculovirus expression system and demonstrated the biological activity of the protein produced. Bombyx mori larvae were infected with B. mori nuclear polyhedrosis virus (BmNPV), modified by inserting a cDNA coding for oIFN-tau downstream of the strong polyhedron promoter. Following infection, antiviral activity of the haemolymph rose to a maximum of 3.6 x 10(8) u/mL (equivalent to 3 mg roIFN-tau/mL) by day 5, when haemolymph was collected and stored frozen. Control haemolymph, collected from uninfected insects at an equivalent time, contained no antiviral activity. The roIFN-tau was partially purified by gel filtration column chromatography and the presence of roIFN-tau confirmed by western blotting. The biological activity of the partially purified roIFN-tau was tested in ewes. Treatment with roIFN-tau caused a significant delay in luteolysis confirming biological potency. The results demonstrate that this system can be successfully used to produce large quantities of roIFN-tau.

Treatment of atheroembolization with corticosteroids.

Aortic atheroembolization is a feared complication of invasive procedures such as arteriography, often leading to devastating complications including renal insufficiency. To date, even in cases with evolving renal failure, there is no recommended treatment. This case report describes the successful treatment with corticosteroids of a patient with deteriorating renal function after renal arteriography and angioplasty, resulting in rapid and sustained improvement in renal function. The implications of this observation are discussed.

Low-dose alpha/beta blockade in the treatment of essential hypertension.

Despite the recent emphasis on combination drug therapy for hypertension, little attention has been given to alpha/beta blockade using agents other than labetalol. The purpose of this study was to 1) compare the efficacy of low-dose alpha/beta blockade using doxazosin + betaxolol, versus monotherapy with an angiotensin converting enzyme inhibitor (quinapril) and a diuretic (hydrochlorothiazide [HCTZ]), and 2) assess the efficacy of low-dose doxazosin. In a crossover study, 21 hypertensive subjects were treated for 3 weeks each with HCTZ, 12.5 to 25 mg/day, quinapril, 10 to 40 mg/day, and a combination of doxazosin, 1 to 4 mg + betaxolol, 5 to 10 mg daily. Doses were titrated to achieve a systolic pressure <130 mm Hg, as assessed by self-recorded home measurements. Home blood pressure decreased 11.5/7.5 mm Hg after HCTZ, 12.9/8.8 mm Hg after quinapril, and 21.2/16.5 mm Hg after doxazosin + betaxolol (P < .001/< .001 v HCTZ and P < .002/< .001 v quinapril). The target systolic pressure was achieved by 33%, 43%, and 71% of subjects, respectively (P = .04 v HCTZ, and .03 v quinapril). Among the 8 subjects in whom doxazosin dosage was increased to the maximum of 4 mg, the mean blood pressure achieved at 4 mg did not differ from that achieved at 2 mg (136/87 v 136/88 mm Hg). We conclude that oral alpha/beta blockade is superior to monotherapy with an angiotensin converting enzyme inhibitor or a diuretic and that maximal or near maximal efficacy can be achieved at a 2-mg dose of doxazosin. Low-dose oral alpha/beta blockade merits greater consideration in the drug therapy of essential hypertension.

The mind/body link in essential hypertension: time for a new paradigm.

The origin of essential hypertension is believed by many to be at least partially emotion-related. A widely held paradigm is that perceived emotional distress raises blood pressure and leads eventually to sustained hypertension. However, decades of research have not provided strong or consistent support for this view. The purpose of this article is to briefly review this research, and to present a very different view of the mind-body link of hypertension. This view focuses on the role of emotions that are not consciously perceived, emotions that are unknowingly kept from conscious awareness, and largely ignored by patients, physicians and research. It suggests that the mind/body connection is often operative when we least suspect it. The evidence for this understanding, and the important implications regarding treatment of hypertension and other unexplained medical conditions with a suspected mind/body link, are discussed.

Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin-aldosterone system in normotensive and hypertensive subjects.

Although beta-adrenergic-blocking drugs suppress the renin system (RAAS), plasma angiotensin II (Ang II) responses during beta-blockade have not been defined. This study quantifies the effects of beta-blockade on the RAAS and examines its impact on prorenin processing by measuring changes in the ratio of plasma renin activity (PRA) to total renin. In normotensive (N = 14) and hypertensive (N = 16) subjects, blood pressure (BP), heart rate, PRA, plasma prorenin, plasma total renin (prorenin + PRA), ratio of PRA to total renin (%PRA), plasma Ang II, and urinary aldosterone were measured before and after 1 week of beta-blockade. Plasma renin activity, Ang II, and urinary aldosterone levels were similar for normotensive and hypertensive subjects. Plasma renin activity correlated with Ang II. Total renin, which is proportional to (pro)renin gene expression, was lower in hypertensive subjects and was inversely related to BP. Beta-blockade decreased BP and heart rate in both groups, with medium- and high-renin hypertensive subjects responding more frequently than those with low renin. Beta-blockade consistently suppressed PRA, Ang II, and aldosterone. Total renin was unchanged, thus, %PRA fell. These results indicate that beta-blockers suppress plasma angiotensin II levels, in parallel with the marked reductions in PRA and urinary aldosterone levels in normotensive and hypertensive subjects. The suppression of Ang II levels was comparable to that produced during angiotensin converting enzyme (ACE) inhibition. However, by reducing prorenin processing to renin, beta-blockers do not stimulate renin secretion, unlike ACE inhibitors and Ang II receptor antagonists. This unique action of beta-blockers has important implications for the treatment of cardiovascular disease.

Severe paroxysmal hypertension (pseudopheochromocytoma): understanding the cause and treatment.

Severe, symptomatic paroxysmal hypertension always generates suspicion of a pheochromocytoma, a catecholamine-secreting tumor. However, most patients with this disorder do not have this tumor and their condition remains undiagnosed and ineffectively treated. This case series, summarizing the course of 21 such patients, suggests a cause and an effective treatment approach. All 21 patients insisted that the paroxysms were not related to stress or emotional distress, initially discouraging consideration of a link to emotions. Nevertheless, with careful psychosocial interviewing, the disorder could be attributed to emotions patients were not aware of, and, therefore, unable to report. Such emotions were related either to previous severe emotional trauma or to a general tendency to keep distressful emotions out of awareness. With treatment based on this understanding, further paroxysms were eliminated in 13 (62%) of 21 patients. Alpha- plus beta-blockade was used, combined, when necessary, with an antidepressant agent, with or without an anxiolytic agent. In 3 cases, the disorder was cured with psychotherapy alone. Because the presenting symptoms are physical rather than emotional, patients present to internists and primary care physicians rather than to psychotherapists. For this reason, more awareness of this disorder in the medical community is needed.

Defensiveness and essential hypertension.

The purpose of this study was to investigate the association between essential hypertension and defensiveness. Fifty normotensive and 74 hypertensive subjects completed the State-Trait Personality Inventory (STPI) and State-Trait Anger Expression Inventory (STAXI) to assess perceived anger and anxiety, and the Marlowe-Crowne Scale of Social Desirability as an indicator of defensiveness. Hypertensive and normotensive groups did not differ in their scores on the anger, anger expression, and anxiety scales. In contrast, Marlowe-Crowne scores were higher in the hypertensive group (18.1+/-5.5 vs. 15.4+/-5.1) (p=0.006). Stepwise logistic regression that included age, gender, BMI, and Marlowe-Crowne scores (dichotomized at 18) showed that a high Marlowe-Crowne score was associated with a relative risk of 3.63 (CI 1.49-8.83) of being hypertensive, independent of age, gender, and BMI. Anger and anxiety scores did not predict hypertensive status and did not affect the relationship between Marlowe-Crowne score and hypertensive status. We conclude that defensiveness is more closely related to essential hypertension than is self-reported anger or anxiety. Better understanding of conscious and unconscious mechanisms of defensiveness are likely to be important in clarifying the link between emotions and hypertension.

Prospective study of simultaneous orthoiodohippurate and diethylenetriaminepentaacetic acid captopril renography. The Einstein/Cornell Collaborative Hypertension Group.

UNLABELLED: Captopril renography (CR) has been established in the past 10 yr as a useful diagnostic test for renovascular hypertension. However, direct comparison of tubular and glomerular tracers, quantitative criteria, comparison of quantitative and qualitative results and the reliability of the results in renal failure have not been described in a systematic, prospective fashion. METHODS: Same-day baseline and CR using 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) and [131I]orthoiodohippurate (OIH) were simultaneously performed in two groups of hypertensive subjects, one with demographically defined essential hypertension (n = 43) and the other (n = 60) with a high prevalence of renovascular disease, defined with angiograms. Quantitative criteria for abnormal CR were derived from results among the subjects with essential hypertension. Qualitative analysis was performed using widely established criteria. RESULTS: There were no statistically significant differences between quantitative and qualitative accuracy, between OIH and DTPA or among quantitative parameters. The best accuracies for quantitative CR were 56% with DTPA (n = 57) and 60% with OIH (n = 60), in both cases using the relative renal uptake parameter. Qualitative CR (n = 60) had accuracies of 43% (DTPA) and 50% (OIH), both hindered by 29 (DTPA) and 25 (OIH) abnormal but nondiagnostic studies. Two false-positive studies were detected. Twenty-seven of 29 nondiagnostic studies were associated with a glomerular filtration rate of <50 ml/min (n = 17), one small kidney (n = 17) and/or bilateral renal artery stenosis (n = 16). Supplemental measurement of in vitro stimulated plasma renin activity insignificantly (p > 0.10) and improved accuracies to 63% (DTPA) and 70% (OIH), without introducing additional false-positive tests. CONCLUSION: Orthoiodohippurate and DTPA have comparable accuracy in prospective simultaneous evaluation of CR. False-positive studies are fewer than 5%. The accuracies of quantitative and qualitative criteria do not differ significantly but may be improved by supplemental use of the in vitro stimulated plasma renin activity. In individuals with renal insufficiency, small kidneys and/or bilateral renal artery disease, up to 48% of CR studies are abnormal but nondiagnostic.

Lacunar stroke in a hypertensive football player: implications in managing hypertension in athletes.

PURPOSE: A 28-year-old hypertensive professional football player suffered a lacunar stroke. Given the rarity of stroke at this young age, the contributory roles of hypertension and competitive athletics merit consideration. CASE SUMMARY: A 28-year-old defensive lineman, with long-standing, albeit recently well-controlled hypertension, experienced slurred speech and veering to his right after a game. Computerized tomography revealed a small internal capsule infarct. Diagnostic investigation, including coagulation profiling, sickle screen, antiphospholipid antibody, carotid imaging, and echocardiography did not reveal a cause. The patient recovered within days with no residual impairment. DISCUSSION: Despite the extreme blood pressure elevation associated with isometric straining in young athletes, stroke almost never occurs. Vascular changes resulting from chronic hypertension and/or marked volume depletion, and hemoconcentration resulting from restricted salt intake, diuretic use, and heavy sweating, offer the only explanations for this stroke. RELEVANCE: The case suggests physicians should exercise caution in using diuretics and salt-restricted diets to treat hypertensive athletes. Guidelines for treatment are discussed.

Severe paroxysmal hypertension. An automatic syndrome and its relationship to repressed emotions.

In most patients with severe and symptomatic paroxysmal hypertension, a pheochromocytoma or other medical cause is rarely identified. This article presents the psychosocial assessment of 10 such patients, in whom the absence of any emotional distress preceding paroxysms had discouraged consideration of any psychological basis. However, a causative role of repressed unreported emotions was strongly suggested by 1) a history of unusually severe emotional trauma in 8 of 10 patients, 2) the absence of feelings related to the trauma, and 3) the prompt and sustained response of 3 patients to psychotherapeutic or psychopharmacologic intervention. These observations suggest that some cases of unexplained paroxysmal hypertension have a psychosomatic etiology and result from repressed rather than perceived and reported emotions. Treatment options are explored.

Isolated elevation of diastolic blood pressure. Real or artifactual?

Not infrequently, blood pressure measurement by the standard auscultatory technique yields a normal systolic pressure with an elevated diastolic pressure. The relatively narrow pulse pressure of such a measurement raises concern about the accuracy of the blood pressure measurement. The purpose of this study was to assess the accuracy of auscultatory blood pressure measurements in patients with an uncommonly narrow pulse pressure, particularly patients with an elevated diastolic but normal systolic pressure. Auscultatory blood pressure measurements were compared with an objective noninvasive standard, called K2 analysis, which has been shown to be more accurate than the auscultatory technique. Blood pressure was measured simultaneously by auscultatory and K2 techniques in 175 subjects. Comparisons were performed (1) in the group as a whole, (2) in four clinical subgroups (normotensive [< 140/< 90 mm Hg, n = 69], hypertensive [> or = 140/> or = 90 mm Hg, n = 53], isolated systolic hypertensive [> or = 140/< 90 mm Hg, n = 38], and isolated diastolic hypertensive [< 140/> or = 90 mm Hg, n = 15]), and (3) in two subgroups whose ratio of pulse pressure to diastolic pressure was greater than or equal to 0.45 (n = 151) or less than 0.45 (n = 24). Subjects in the isolated diastolic hypertensive group and in the group with a pulse pressure ratio less than 0.45 were considered to have a narrow pulse pressure. In the group as a whole, consistent with previous auscultatory-K2 comparisons, systolic pressure was slightly higher and diastolic pressure slightly lower when measured by K2 versus the auscultatory technique (auscultatory, 145/85 mm Hg; K2, 147/83 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)