A Comparative Study of Uterine Artery Doppler Parameters and Endometrial Characteristics in Women with Unexplained Infertility and Fertile Women at a Nigerian Teaching Hospital.

OBJECTIVES: To investigate the uterine artery Doppler parameters and endometrial characteristics in women with unexplained infertility. METHODS: A prospective case-control study of 42 women with unexplained infertility and 42 fertile controls. Their mid-luteal phase transvaginal Doppler parameters of both uterine arteries and endometrial characteristics (endometrial blood flow, thickness and volume) were investigated and analysed. P values < 0.05 was statistically significant. RESULTS: The mean uterine artery pulsatility index (PI) and resistivity index (RI) of the cases (women with unexplained infertility) were significantly higher compared to the values in the fertile controls (PI = 2.81±0.61 vs 2.15±0.65; p=0.001) (RI= 0.87±0.08 vs 0.82±0.07; p=0.003). In addition, the end-diastolic volume (EDV) (6.12±4.17 vs 9.37±5.14; p=0.007) and endometrial-subendometrial blood flow (p=0.036) were significantly lower in the cases compared to the controls. Multivariate logistics analysis showed that PI was independently associated with infertile status (p=0.006). There was no significant difference in the mean PSV (48.69±10.9 vs 50.58±11.30; p=0.602), endometrial thickness (10.30+3.13 vs 10.72+3.10; p=0.544), endometrial volume (7.82+1.56 vs 8.23+1.71; p=0.323), mean age (32.28±4.062 vs 31.91±3.58 years; p=0.502), body mass index (26.15±2.71kg/m2 vs 25.24±2.85 kg/m2; p=0.18) menstrual bleeding days (4.07±0.89 days vs 4.02±0.95 days; p=0.481) duration of menstrual cycle (28.02±1.09 days vs 27.64±1.36 days; p= 0.162), smoking history (p=0.909) and alcohol intake (p=0.507) of the infertile women compared with the fertile controls, respectively. CONCLUSION: Women with unexplained infertility have increased uterine artery Doppler PI and RI and reduced endometrial-subendometrial perfusion compared with fertile controls.

OBJECTIFS: Étudier les paramètres Doppler de l'artère utérine et les caractéristiques de l'endomètre chez les femmes atteintes d'infertilité inexpliquée. MÉTHODES: Une étude cas-témoins prospective de 42 femmes atteintes d' infertilité inexpliquée et 42 témoins fertiles. Leur phase mi-lutéaleles paramètres Doppler transvaginaux des artères utérines et des caractéristiques de l'endomètre (flux sanguin de l'endomètre, épaisseur et volume) ont été étudiés et analysés.Les valeurs P d ¼ 0,05 étaient statistiquement significatives. RÉSULTATS: L'indice moyen de pulsatilité de l'artère utérine (IP) etindice de résistivité (IR) des cas (femmes atteintes d'infertilité inexpliquée)étaient significativement plus élevées par rapport auxvaleurs des témoins fertiles(PI = 2,81±0,61 vs 2,15±0,65; p = 0,001) (RI = 0,87±0,08 vs0,82±0,07; p=0,003). De plus, le volume diastolique final (EDV)(6,12±4,17 vs 9,37±5,14; p = 0,007) et endométrialesous-endomètrele débit sanguin (p = 0,036) était significativement plus faible dans les cas comparésaux contrôles. L'analyse logistique multivariée a montré que PI était indépendamment associé au statut infertile (p = 0,006).Il n'y avait pas de différence significative dans le PSV moyen (48,69±10,9 vs50 h 58±11 h 30; p=0,602), épaisseur de l'endomètre (10,30+3,13 vs10.72+3.10; p = 0,544), volume de l'endomètre (7,82 + 1,56 vs 8,23 + 1,71;p=0,323), âge moyen (32,28±4,062 vs 31,91±3,58 ans; p=0,502),indice de masse corporelle (26,15±2,71 kg/m2 vs 25,24±2,85 kg/m2; p=0,18)jours de saignements menstruels (4,07±0,89 jours vs 4,02±0,95 jours; p = 0,481)durée du cycle menstruel (28,02±1,09 jours vs 27,64±1,36 jours;p= 0,162), antécédents de tabagisme (p = 0,909) et consommation d'alcool (p = 0,507)des femmes infertiles par rapport aux témoins fertiles, respectivement. CONCLUSION: Les femmes atteintes d'infertilité inexpliquée ont augmentation significative de l'artère utérine Doppler PI et RI et réduction perfusion endométriale-sous-endoudo-endométrique par rapport aux témoins fertiles. Mots-clés: Infertilité inexpliquée, Artère utérine, Doppler, Caractéristiques de l'endomètre.

Staufen 1 is expressed by neural precursor cells in the developing murine cortex but is dispensable for NPC self-renewal and neuronal differentiation in vitro.

BACKGROUND: Proper development of the cerebral cortex relies on asymmetric divisions of neural precursor cells (NPCs) to produce a recurring NPC and a differentiated neuron. Asymmetric divisions are promoted by the differential localization of cell-fate determinants, such as mRNA, between daughter cells. Staufen 1 (Stau1) is an RNA-binding protein known to localize mRNA in mature hippocampal neurons. Its expression pattern and role in the developing mammalian cortex remains unknown. RESULTS: Both stau1 mRNA and Stau1 protein were found to be expressed in all cells of the developing murine cortex. Stau1 protein expression was characterized spatially and temporally throughout cortical development and found to be present in all stages investigated. We observed expression in the nucleus, cytoplasm and distal processes of both NPCs and newly born neurons and found it to shuttle between the nucleus and the cytoplasm. Upon shRNA-mediated knock-down of Stau1 in primary cultures of the developing cortex, we did not observe any phenotype in NPCs. They were able to both self-renew and generate neurons in the absence of Stau1 expression. CONCLUSIONS: We propose that Stau1 is either dispensable for the development of the cerebral cortex or that its paralogue, Stau2, is able to compensate for its loss.

Microplastic accumulation and biomagnification in a coastal marine reserve situated in a sparsely populated area.

Toxic chemicals within and adsorbed to microplastics (0.05-5 mm) have the potential to biomagnify in food webs. However, microplastic concentrations in highly productive, coastal habitats are not well understood. Therefore, we quantified the presence of microplastics in a benthic community and surrounding environment of a remote marine reserve on the open coast of California, USA. Concentrations of microplastic particles in seawater were 36.59 plastics/L and in sediments were 0.227 ±â€¯0.135 plastics/g. Densities of microplastics on the surfaces of two morphologically distinct species of macroalgae were 2.34 ±â€¯2.19 plastics/g (Pelvetiopsis limitata) and 8.65 ±â€¯6.44 plastics/g (Endocladia muricata). Densities were highest in the herbivorous snail, Tegula funebralis, at 9.91 ±â€¯6.31 plastics/g, potentially due to bioaccumulation. This study highlights the need for further investigations of the prevalence and potential harm of microplastics in benthic communities at remote locations as well as human population centers.

Preventing adolescent suicide: A systematic review of the effectiveness and change mechanisms of suicide prevention gatekeeping training programs for teachers and parents.

INTRODUCTION: Suicide is a leading cause of death in young people, which may in part be because young people are notoriously poor help-seekers. Improving the identification of at-risk young people and connecting them to appropriate help is needed to prevent suicide in adolescents. The aim of this study is to examine the effectiveness of suicide prevention gatekeeper programs for parents and teachers, which are designed to improve their ability to recognise and respond to risks so that they may intervene before crisis occurs. METHODS: Academic databases and reference lists were searched for gatekeeper training programs involving teachers and parents, and which aimed to prevent youth suicide, between journal inception and May 2018. Information directly reporting on suicide literacy (knowledge, confidence, attitudes) and/or gatekeeper behaviours (identification, referral) was extracted and a qualitative synthesis was conducted. RESULTS: Thirteen studies fulfilled inclusion criteria. Significant moderate-to-large intervention effects were reported for suicide literacy outcomes among teachers and parents, with the largest gains among those with lowest baseline scores. No improvements in identification and referral behaviors among gatekeepers were noted. A need to improve evaluation research designs and outcome measurements was evident. CONCLUSIONS: While gatekeeper programs lead to increased suicide literacy, there is little evidence for behavioural change. There is need to increase the reach and uptake of gatekeeper training by offering digital versions, which may lead to improved behavioural outcomes, and to employ targeted strategies to engage parents in this training as one of the most trusted sources of support for vulnerable youth.

Effect of stocking density on performance, diet selection, total-tract digestion, and nitrogen balance among heifers grazing cool-season annual forages.

Grazing annual cool-season forages after oat grain harvest in South Dakota may allow an opportunity to increase efficient use of tillable land. However, data are limited regarding effects of stocking density on diet selection, nutrient digestion, performance, and N retention by cattle grazing annual cool-season forage. Heifers were blocked by initial BW (261 ± 11.7 kg) and randomly assigned to 1 of 12 paddocks (1.1 ha) to graze a mixture of grass and brassica for 48 d. Each paddock contained 3, 4, or 5 heifers to achieve 4 replicates of each stocking density treatment. Ruminally cannulated heifers were used to measure diet and nutrient intake. Effects of stocking density on diet and nutrient selection were measured after 2, 24, and 46 d of grazing, and BW was measured at the beginning, middle, and end of the experiment as the average of d 1 and 2, d 22 and 23, and d 47 and 48 BW, respectively. Measures of DMI and DM, OM, NDF, and ADF digestion were collected from d 18 to 23. Increased stocking density increased intake of brassica relative to grass on d 24 (quadratic, = 0.02), but increased stocking density decreased (linear, ≤ 0.01) intake of brassica compared with grass on d 48 (stocking density × time, < 0.01). Increased stocking density increased DM (quadratic, < 0.01), OM (quadratic, = 0.01), and NDF (quadratic, = 0.05) digestion, and stocking density tended to increase DMI (quadratic, = 0.07). Additionally, increased stocking density quadratically increased ( = 0.05) N retention but did not affect overall BW gains. Increased stocking density did, however, contribute to linearly decreased ( = 0.05) BW gains from d 1 to 22 of grazing, but BW gains during the latter half of the experiment were greater than BW gains from d 1 to 22. Ruminal concentration of acetate:propionate was least on d 24 of grazing, and ruminal nitrate concentration tended to linearly decrease ( = 0.06) with greater amounts of time on pasture. Ruminal liquid and particulate fill and amounts of VFA were less (quadratic, ≤ 0.01) with greater amounts of time on pasture. Apparently, binary mixtures of brassica and grass planted after oat grain harvest can provide an opportunity to increase efficient use of land by providing forage resources. Increased stocking density may facilitate a more rapid adaptation to and intake of brassica among cattle grazing brassica-grass-based pastures.

Molecular survey of trichostrongyle nematodes in a Bison bison herd experiencing clinical parasitism, and effects of avermectin treatment.

North American bison (Bison bison) producers face many challenges, including the potential clinical and economics problems caused by trichostrongyle nematodes within their herds. Little is known about the prevalence, intensity, geographical distribution and clinical significance of these parasites in commercial bison herds, even from regions where bison production has become popular. This study involved a large herd of bison from eastern South Dakota that was experiencing clinical parasitism due to a temporary over-stocking problem. After documenting fecal egg counts (FECs) and trichostrongyle genera present among the 3 main age-categories (i.e. adults, yearlings, calves) of bison during this heavily infected grazing season, the effects of doramectin treatment on the different age groups was also evaluated. This is the first bison study using PCR to identify genera of trichostrongyles in fecal samples. Virtually all 103 bison fecal samples from all 3 age classes were shedding trichostrongyle eggs by the end of the season, and the mean FECs were 34 eggs/g (EPG) among the cows, 125 EPG in the yearlings, and 186 EGP among calves. Based upon this heavily-infected herd, there is evidence that the susceptibility of bison to trichostrongyles is more similar to beef cattle than to sheep. Other parasites such as Moniezia, Nematodirus, Trichuris, and coccidians were also identified in these samples. All but 3 of the 51 samples analyzed with PCR shown at least 1 trichostrongyle genera. Ostertagia was detected in 68.6% of the samples, Cooperia in 80.39%, Haemonchus in at least 73% and Trichostrongylus in 16% of the herd. Most commonly, bison were infected with combinations of Haemonchus/Ostertagia/Cooperia. After treatment with doramectin, the mean FECs dropped by 99.9% for all of the bison age classes.

Outcome of surgery for chronic patellar tendinopathy: A systematic review.

There is no consensus on how to best surgically treat chronic patellar tendinopathy. This systematic review investigates the surgical treatment for chronic patellar tendinopathy, and the outcomes. A database search was performed to identify all relevant articles, to which exclusion criteria were then applied. Data was extracted from 24 studies, and the outcomes were then systematically reviewed. The results showed that the success rate of surgery for patellar tendinopathy is generally over 77%. Return to sports rates are better for proximal tendon patients who undergo bony procedures. Patients return to sports faster if they undergo arthroscopic procedures, and fewer complications are described. Studies that did not involve any procedure on the proximal tendon did not produce a different result to studies where the tendon was operated on. We found no effect of post-operative immobilisation on outcome. Based on the included studies, surgery gives satisfactory results in the treatment of patellar tendinopathy. There is a lack of high-quality evidence on the effects of surgery and post-operative rehabilitation regime on chronic patellar tendinopathy, as well as lack of objective outcome measures.

Influence of feeding various quantities of wet and dry distillers grains to finishing steers on carcass characteristics, meat quality, retail-case life of ground beef, and fatty acid profile of longissimus muscle.

Two hundred forty Angus crossbred steers were used to determine the influence of feeding various quantities of wet and dry distillers grains to finishing steers on carcass characteristics, meat quality, retail-case life of ground beef, and fatty acid profile of LM. Three replications of 5 dietary treatments were randomly applied to 15 pens in each of 2 yr. A finishing diet containing dry-rolled corn, soybean meal, and alfalfa hay was fed as the control diet. Wet distillers grains with solubles (DGS) or dry DGS was added to the finishing diets at either 20.0 or 40.0% of the dietary DM to replace all soybean meal and part of the cracked corn in treatment diets. Carcasses of steers fed DGS had greater (P < 0.05) fat thickness (1.47 vs. 1.28 cm), greater (P < 0.05) USDA yield grades (3.23 vs. 2.94), and smaller (P < 0.05) percentage of yield grades 1 and 2 (41.1 vs. 60.4%) than carcasses of steers fed the control diet. Longissimus muscle from steers fed dry DGS had greater (P < 0.05) ultimate pH values (5.52 vs. 5.49) than LM from steers fed wet DGS. Ground beef from steers fed DGS had greater (P < 0.05) concentrations of α-tocopherol (1.77 vs. 1.43 µg/g) than ground beef from steers fed the control diet. Ground beef from steers fed 40% DGS had greater (P < 0.05) thiobarbituric acid-reactive substances (2.84 vs. 2.13 mg/kg) on d 2 of retail display than ground beef from steers fed 20% DGS. Longissimus muscle of steers fed DGS had less (P < 0.05) C17:0 and more (P < 0.05) C18:0, C18:1t, C16:1c9, C18:2c9c12 (where t is trans and c is cis), and total PUFA than LM of steers fed the control diet. Feedlot steers fed DGS may need to be marketed earlier than normal to avoid excess external fat and carcasses with a greater numerical yield grade. These data suggest feeding DGS to finishing steers will have no adverse or beneficial effects on glycolytic variables (dark cutters), retail display life of ground beef, or meat tenderness. However, beef from cattle finished on diets containing DGS will likely have a greater proportion of PUFA and therefore may be more susceptible to oxidative rancidity.

Circulating ghrelin concentrations fluctuate relative to nutritional status and influence feeding behavior in cattle.

The objective of these experiments was to establish the relationship of plasma ghrelin concentrations with feed intake and hormones indicative of nutritional state of cattle. In Exp.1, 4 steers (BW 450 +/- 14.3 kg) were used in a crossover design to compare plasma ghrelin concentrations of feed-deprived steers with those of steers allowed to consume feed and to establish the relationship of plasma ghrelin concentrations with those of GH, insulin (INS), glucose (GLU), and NEFA. After adaptation to a once-daily feed offering (0800), 2 steers continued the once-daily feeding schedule (FED), whereas feed was withheld from the other 2 steers (FAST). Serial blood samples were collected via indwelling jugular catheter from times equivalent to 22 h through 48 h of feed deprivation. Average plasma ghrelin concentrations were greater (P < 0.001) in FAST compared with FED (690 and 123 +/- 6.5 pg/mL) steers. Average plasma ghrelin concentrations for FED steers prefeeding were elevated (P < 0.001) when compared with those postfeeding (174 and 102 +/- 4.2 pg/mL, respectively). Average plasma GH concentration was elevated (P < 0.05) for FAST steers compared with FED steers. Plasma GLU concentrations were not different; however, for FAST steers, NEFA concentrations were elevated (P < 0.001) and INS concentrations were decreased (P < 0.001). In Exp. 2, 4 steers (BW 416 +/- 17.2 kg) were used in a crossover design to determine the effects of i.v. injection of bovine ghrelin (bGR) on plasma GH, INS, GLU, and NEFA concentrations; length of time spent eating; and DMI. Steers were offered feed once daily (0800). Serial blood samples were collected from steers via indwelling jugular catheter. Saline or bGR was injected via jugular catheter at 1200 and 1400. A dosage of 0.08 microg/kg of BW bGR was used to achieve a plasma ghrelin concentration similar to the physiological concentration measured in a FAST steer in Exp. 1 (1,000 pg/mL). Injection of bGR resulted in elevated (P < 0.005) plasma GH concentrations after the 1200 but not the 1400 injection. Plasma INS, GLU, and NEFA concentrations were not affected by bGR injection. For the combined 1-h periods postinjection, length of time spent eating was greater (P = 0.02) and DMI tended to be increased (P = 0.06) for bGR steers. These data are consistent with the hypothesis that ghrelin serves as a metabolic signal for feed intake or energy balance in ruminants.

Photon correlation and scattering: introduction to the feature issue.

This feature issue of Applied Optics contains 31 research papers on photon correlation and scattering, many of which were presented at an OSA Topical Meeting that was held 21-23 August 2000 in Whistler, British Columbia, Canada. These papers focus on research in dynamic light scattering, surface light scattering, photon correlation, and laser velocimetry and their applications to physical, chemical, and biological processes.

Quantitative simulation of errors in correlation analysis.

Bounding the errors of measurements derived from correlation functions of light scattered from some physical systems is typically complicated by the ill conditioning of the data inversion. Parameter values are estimated from fitting well-chosen models to measurements taken for long enough to look acceptable, or at least to yield convergence to some reasonable result. We show some simple numerical simulations that indicate the possibility of substantial and unanticipated errors even in comparatively simple experiments. We further show quantitative evidence for the effectiveness of a number of ad hoc aspects of the art of performing good light-scattering experiments and recovering useful measurements from them. Separating data-inversion properties from experimental inconsistencies may lead to a better understanding and better bounding of some errors, giving new ways to improve overall experimental accuracy.

Human skin absorption and metabolism of the contact allergens, cinnamic aldehyde, and cinnamic alcohol.

trans-Cinnamaldehyde and trans-cinnamic alcohol have been commonly reported to cause allergic contact dermatitis (ACD) in humans. Cinnamaldehyde is a more potent skin sensitizer than cinnamic alcohol. It has been hypothesized that cinnamic alcohol is a "prohapten" that requires metabolic activation, presumably by oxidoreductase enzymes such as alcohol dehydrogenase (ADH) or cytochrome P450 2E1 (CYP2E1), to the protein-reactive cinnamaldehyde (a hapten). In this study, the in vitro percutaneous absorption and metabolism of cinnamaldehyde and cinnamic alcohol (78 micromol dose) has been examined using freshly excised, metabolically viable, full-thickness breast and abdomen skin from six female donors. Penetration rates and total cumulative recoveries of cinnamic compounds that were present in receptor fluid, extracted from within the skin, evaporated from the skin surface, or remained unabsorbed on the skin surface after 24 h were quantified by reversed-phase high-performance liquid chromatography. Biotransformation of cinnamaldehyde to both cinnamic alcohol and cinnamic acid was observed. Topically applied cinnamic alcohol was converted to cinnamaldehyde (found on the skin surface only) and cinnamic acid. To establish whether these biotransformations were enzymatic, experiments were performed in the absence and presence of varying concentrations (80-320 micromol) of the ADH/CYP2E1 inhibitors pyrazole or 4-methylpyrazole. The observation that pyrazole significantly reduced (p < 0.05) the total penetration of cinnamic metabolites into receptor fluid, following either cinnamaldehyde or cinnamic alcohol treatment, but did not significantly affect parent chemical penetration, suggests that we are measuring cutaneous metabolic products of ADH activity. The skin absorption and metabolism of cinnamaldehyde and cinnamic alcohol will play an important role in the manifestation of ACD following topical exposure to these compounds.

Renin expression in COX-2-knockout mice on normal or low-salt diets.

Experiments were performed in mice to investigate whether cyclooxygenase-2 (COX-2) in epithelial cells near the tubulovascular contact point (macula densa and TAL cells) may regulate renin gene expression in juxtaglomerular granular cells. Renin activity, afferent arteriolar granularity, and renin mRNA were determined in wild-type mice and in COX-2-knockout mice on control and low-NaCl diets. Renin activity in microdissected glomeruli assessed as angiotensin I formation in the presence of excess substrate and afferent arteriolar granularity determined by direct visualization and immunostaining were significantly reduced in COX-2 -/- compared with wild-type animals. Similarly, renal cortical mRNA levels were lower in COX-2 -/- than in wild-type mice. Maintaining mice on a low-salt diet for 14 days induced an increase in renin mRNA, afferent arteriolar granularity, and renin activity in wild-type mice. In contrast, renin mRNA and renin granularity did not significantly increase in low-salt-treated COX-2 -/- mice, whereas the increase in juxtaglomerular renin enzyme activity was markedly attenuated, but not fully blocked. In additional experiments we found that COX-2 mRNA was increased in angiotensin type 1A receptor-knockout mice compared with wild-type mice. We conclude that COX-2 in the tubulovascular contact region is a critical determinant of renin synthesis in granular cells under resting conditions and that it participates in the stimulation of renin expression caused by a low-NaCl intake.

Thyroid hormone resistance and increased metabolic rate in the RXR-gamma-deficient mouse.

Vitamin A and retinoids affect pituitary-thyroid function through suppression of serum thyroid-stimulating hormone (TSH) levels and TSH-beta subunit gene expression. We have previously shown that retinoid X receptor-selective (RXR-selective) ligands can suppress serum TSH levels in vivo and TSH-beta promoter activity in vitro. The RXR-gamma isotype has limited tissue distribution that includes the thyrotrope cells of the anterior pituitary gland. In this study, we have performed a detailed analysis of the pituitary-thyroid function of mice lacking the gene for the RXR-gamma isotype. These mice had significantly higher serum T4 levels and TSH levels than did wild-type (WT) controls. Treatment of RXR-gamma-deficient and WT mice with T3 suppressed serum TSH and T4 levels in both groups, but RXR-gamma-deficient mice were relatively resistant to exogenous T3. RXR-gamma-deficient mice had significantly higher metabolic rates than did WT controls, suggesting that these animals have a pattern of central resistance to thyroid hormone. RXR-gamma, which is also expressed in skeletal muscle and the hypothalamus, may have a direct effect on muscle metabolism, regulation of food intake, or thyrotropin-releasing hormone levels in the hypothalamus. In conclusion, the RXR-gamma isotype appears to contribute to the regulation of serum TSH and T4 levels and to affect peripheral metabolism through regulation of the hypothalamic-pituitary-thyroid axis or through direct effects on skeletal muscle.

Expression of peroxisomal proliferator-activated receptors and retinoid X receptors in the kidney.

The discovery that 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) is a ligand for the gamma-isoform of peroxisome proliferator-activated receptor (PPAR) suggests nuclear signaling by prostaglandins. Studies were undertaken to determine the nephron localization of PPAR isoforms and their heterodimer partners, retinoid X receptors (RXR), and to evaluate the function of this system in the kidney. PPARalpha mRNA, determined by RT-PCR, was found predominately in cortex and further localized to proximal convoluted tubule (PCT); PPARgamma was abundant in renal inner medulla, localized to inner medullary collecting duct (IMCD) and renal medullary interstitial cells (RMIC); PPARbeta, the ubiquitous form of PPAR, was abundant in all nephron segments examined. RXRalpha was localized to PCT and IMCD, whereas RXRbeta was expressed in almost all nephron segments examined. mRNA expression of acyl-CoA synthase (ACS), a known PPAR target gene, was stimulated in renal cortex of rats fed with fenofibrate, but the expression was not significantly altered in either cortex or inner medulla of rats fed with troglitazone. In cultured RMIC cells, both troglitazone and 15d-PGJ2 significantly inhibited cell proliferation and dramatically altered cell shape by induction of cell process formation. We conclude that PPAR and RXR isoforms are expressed in a nephron segment-specific manner, suggesting distinct functions, with PPARalpha being involved in energy metabolism through regulating ACS in PCT and with PPARgamma being involved in modulating RMIC growth and differentiation.

Inhibition of macula densa-stimulated renin secretion by pharmacological blockade of cyclooxygenase-2.

Previous results from our laboratory have shown that in the isolated perfused juxtaglomerular apparatus, nonselective inhibitors of cyclooxygenase (COX) activity prevent the stimulation of renin secretion by a reduction in luminal NaCl concentration at the macula densa. The present studies were performed to examine which COX isoform is involved in NaCl-dependent renin secretion. In the absence of COX inhibitors, a reduction in luminal NaCl (from Na 141/Cl 120 mM to Na 26/Cl 7 mM) caused an increase in renin secretion rate from 4.5 +/- 1.8 to 26.1 +/- 7.4 nGU/min (P < 0.01, n = 19). The presence of the COX-1 inhibitor valerylsalicylate (500 microM) in lumen and bath did not affect the stimulation of renin secretion by a reduction in luminal NaCl concentration (5 +/- 1.8 nGU/min at high NaCl, and 30.5 +/- 9.4 nGU/min at low NaCl; P < 0.01, n = 8). In contrast, the specific COX-2 inhibitor NS-398 (50 microM) in lumen and bath abolished the stimulating effect of low luminal NaCl (12.8 +/- 3.9 nGU/min at high NaCl, and 10.7 +/- 3.1 nGU/min at low NaCl; NS, n = 15). The finding that COX-2 is critically involved in macula densa control of renin secretion indicates that the COX-2-expressing epithelial cells in the tubuloglomerular contact area are a likely source of prostaglandins participating in the signaling pathway between the macula densa and renin-producing granular cells.

Differential regulation of COX-2 expression in the kidney by lipopolysaccharide: role of CD14.

Induction of the inducible cyclooxygenase isoform COX-2 is likely to be an important mechanism for increased prostaglandin production in renal inflammation. We examined the effect of lipopolysaccharide (LPS) on regional renal COX-2 expression in the rat. In the inner medulla, LPS injection (4 mg/kg ip) induced a twofold and 2.5-fold increase in the levels of COX-2 mRNA and COX-2 protein, respectively. In contrast, COX-2 expression in the renal cortex was not significantly altered. COX-2 promoter transgenic mice were created using the 2.7-kb flanking region of the rat COX-2 gene. In these animals, LPS injection induced reporter gene expression predominately in the inner medulla. The LPS receptor CD14, usually regarded as a monocyte/macrophage-specific marker, was found to be abundantly expressed in the inner medulla and in dissected inner medullary collecting duct (IMCD) cells, suggesting that it may mediate medullary COX-2 induction. CD14 was present only at low levels in cortex and cortical segments, including glomeruli. In cultured cells, it was abundant in mouse IMCD (mIMCD-K2) cells and renal medullary interstitial cells, but largely undetectable in mesangial cells and M1 cells, a cell line derived from mouse cortical collecting ducts. In the mIMCD-K2 cell line, LPS significantly induced COX-2 mRNA expression, with concomitant induction of CD14. LPS-stimulated COX-2 expression was reduced by the addition of an anti-CD14 monoclonal antibody to the culture medium. These results demonstrate that LPS selectively stimulates COX-2 expression in the renal inner medulla through a CD14-dependent mechanism.

Metanephric rat-mouse chimeras to study cell lineage of the nephron.

The nephron is derived from the ureteric bud and metanephric mesenchyme and develops into a complex epithelial structure with a wide variety of phenotypes along its length. This segmental variation in expression of molecules provides an approach to understand the lineage of unique segments. The present study evaluated the expression of four relatively well-localized molecules--renin, Tamm-Horsfall protein (THP), oxytocin receptor (OTR), and the vasopressin type 2 receptor (V2R)--in cultured mouse-rat chimeric metanephric kidneys using reverse transcription-polymerase chain reaction (RT-PCR). Chimeric kidneys were formed by 1) separating the ureteric bud (U) from the metanephric mesenchyme (M) of mouse (m) at E11 and rat (r) at E13 days of gestation and 2) recombining the ureteric bud of one species with the metanephric mesenchyme of the other species (i.e., UrMm and UmM(r), followed by filter culture until differentiated. Species-specific restriction enzymes for all four genes were chosen to digest the PCR product from either rat or mouse. RT-PCR was performed for each mRNA species and the products digested. The V2R product from the UrMm chimera was cleaved by a restriction enzyme known to digest only rat product, suggesting the PCR product was produced predominantly by cells derived from the ureteric bud. The renin, OTR, and THP products from both chimeras were cleaved equally well by species-specific restriction enzymes, suggesting the products were made by cells originating from both the ureteric bud and the metanephric mesenchyme. These studies demonstrate that the cultured chimeric metanephric model is useful to study segment lineage. The results suggest that the lineage of at least certain portions of the nephron is heterogenous.

Hypertension management of medical aid patients attending private practices.

OBJECTIVES: The study aimed to describe the treatment status of hypertensive patients and the prescribing patterns of private medical practitioners treating medical aid scheme patients with hypertension. METHOD: Data on hypertensive patients belonging to medical aid schemes were provided to the drug utilisation review consultancy, Quality Health Services (QHS), by private medical practitioners. The data were computerised and included the age and gender of the patient, the diastolic and systolic blood pressure (BP), the medication prescribed for the condition and the qualifications of the reporting doctor. All the prescribed drugs were categorised into 12 drug classes and combination preparations had each constituent categorised. The level of BP allowed the degree of BP control to be described as controlled (< 140/90 mmHg), borderline (140/90-< 160/95 mmHg) and uncontrolled (> or = 160/95 mmHg). RESULTS: Included in the study were 11,696 hypertensive patients (46.3% male and 53.7% female) and the 3,503 doctors who cared for them. The systolic BP showed an age-related increase, but the diastolic BP did not. The level of BP control was high, with less than a quarter of patients having uncontrolled hypertension. The most frequently prescribed drug class was angiotensin-converting enzyme (ACE) inhibitors (32.2%). Beta-blockers accounted for 20.8% and calcium antagonists for 14% of all prescriptions. Thiazide and thiazide-like diuretics on their own accounted for only 7.8% of prescriptions. However, a further 13.8% of prescriptions contained this class of diuretics in combination with other drug classes. Diuretics of all classes taken on their own or in combination were used by 33.9% of patients. CONCLUSIONS: Good levels of hypertension control were reported for hypertensive patients by their private practitioners. Almost half of all prescriptions were for the newer and more costly antihypertensive drugs (ACE inhibitors and calcium antagonists), although their effectiveness in reducing long-term complications of hypertension is still unproven. Furthermore, these prescribing patterns do not conform to those recommended by the Southern African Hypertension Society's hypertension management guidelines.

Particle sizing in strongly turbid suspensions with the one-beam cross-correlation dynamic light-scattering technique.

The utility of the one-beam cross-correlation dynamic light-scattering system for sizing small particles in suspension was previously limited by its small-intensity signal-to-baseline ratio for strongly turbid suspensions. We describe three improvements in the optical system and sample cell that raise the ratio to a value comparable with that of other cross-correlation dynamic light-scattering systems. These improvements are (i) using a square cross-sectional sample cell to minimize the attenuation of the incident beam and singly scattered light, (ii) placing a 200-microm-wide slit between the sample cell and the detector fibers to mask off the region of weak single scattering and strong multiple scattering from the detectors' field of view, and (iii) aligning the center of the detectors' field of view with the region of strongest single scattering. We analyze a number of suspensions of polystyrene latex spheres with a diameter between 65 and 562 nm in water using this improved one-beam instrument and find that the measured radius is determined in a 2-min data collection time to better than +/-10% for volume fractions of the suspended polystyrene latex spheres up to a few percent.