Treatment with eCG and hCG to induce onset of estrous cycles in ewes during the non-breeding season: Effects on follicular development and fertility.

Although combining of eCG and hCG administrations is known to enhance LH-like actions, there have been few studies where there was comparison of the effects of treatment of anestrous ewes with eCG and hCG and eCG alone. In Experiment 1, 18 ewes in seasonal anestrus were administered an intravaginal device (IVD) containing medroxyprogesterone acetate for 12 days, and at the time of IVD removal (D0), were allocated into the following groups (n = 6/group): no further treatment (control); 400 IU eCG (eCG); or 400 IU eCG and 200 IU hCG (eCG + hCG). There was greater ovarian follicular growth in the groups treated with gonadotropins, compared to the control, and there were greater progesterone concentrations in the eCG + hCG group on D9 (P < 0.05). In Experiment 2, 66 ewe lambs were assigned to the same treatment groups described for Experiment 1, and subsequently there was natural mating with rams. There was a greater rate of behavioral estrous manifestation in the eCG (88.5 %; 23/26) and eCG+hCG (85.2 %; 23/27), than control (30.8 %; 4/13; P < 0.05) group. Pregnancy rate was also greater in the eCG (34.6 %; 9/26) and eCG+hCG (18.6 %; 5/27) than control (0 %; 0/13; P < 0.05) group, whereas conception rate, considering only ewe lambs that were mated, was only greater in the eCG group. Although there were greater progesterone concentrations 9 days after treatment in the eCG+hCG group, there was no difference in follicular growth in anestrous ewes, nor was there an effect on estrous behavior manifestation and pregnancy rates in ewe lambs, compared to treatment with only eCG.

Expression of paraoxonase types 1, 2 and 3 in reproductive tissues and activity of paraoxonase type 1 in the serum and seminal plasma of bulls.

The paraoxonases types 1, 2 and 3 (PON1, PON2 and PON3, respectively) are enzymes that degrade lipid peroxides, preventing oxidative damages relevant for male reproductive function. This study determined the expression of those three paraoxonases in reproductive tissues of bulls and evaluated correlations among the activity of PON1 in the serum and seminal plasma with breeding soundness parameters in bulls. The expression of PON1, PON2 and PON3 was characterised by RT-PCR in samples of testicular parenchyma, vesicular glands and epididymis collected from three slaughtered bulls. All three paraoxonases were expressed in the testicular parenchyma, PON2 and PON3 were both expressed in the epididymis head and PON3 was also expressed in the epididymis tail. The PON1 activity was determined in samples of serum and seminal plasma from 110 bulls submitted to breeding soundness evaluation. There was a strong correlation (r = .90) between the activity of the PON1 in both serum and seminal plasma (p < .0001). The PON1 activity in the seminal plasma was positively correlated with ejaculate's colour, sperm mass activity (p = .04), motility, vigour and viability (all p < .01). Thus, PON1 may be a potential marker for sperm motility and viability in bulls.

Low Impact of Urinary Cortisol in the Assessment of Hydrocortisone Replacement Therapy.

Hydrocortisone replacement therapy is a cornerstone in the treatment of adrenal insufficiency (AI). While urinary cortisol has been used as a diagnostic tool for AI, it remains unclear whether it is a useful parameter to monitor hydrocortisone replacement therapy. Aim of this study was to evaluate possible differences in cortisol metabolism between adrenal insufficient patients and healthy subjects and to assess the value of urinary cortisol in AI management. In a case-control study, urinary cortisol excretion was determined in 14 patients with primary and secondary AI receiving hydrocortisone infusions from midnight to 8:00 AM. Results were correlated with serum cortisol levels and compared to urinary values obtained from 53 healthy volunteers. Urinary cortisol excretion in healthy subjects was 14.0±7.8 µg/8 h (range: 0.24-35.4), levels did not differ between 3 groups aged 20-34 years, 35-49 years, and ≥50 years. Patients with AI receiving hydrocortisone infusions demonstrated significantly higher rates of urinary cortisol excretion (51.6±37.8 µg/8 h; range 17.1-120.0, p<0.001); the values correlated with serum cortisol levels (r(2)=0.98). Of interest, patients with secondary AI showed significantly higher serum cortisol levels after hydrocortisone infusion than those with primary AI, conceivably due to residual adrenal function. In conclusion, we showed that: (i) there is a wide inter-individual variability in urinary cortisol excretion rates; (ii) cortisol metabolism in adrenal insufficient patients differs when compared to controls; (iii) there is a strong correlation between urinary and serum cortisol levels; and (iv) urinary cortisol levels despite their variability may help to discriminate between secondary and primary adrenal insufficiency.

Headache and Depression in Patients with Hypothalamic-pituitary Disorders-etiology and Risk Factors.

INTRODUCTION: Headache and depression are common problems in patients with hypothalamic-pituitary disorders (HPD). AIM: To determine the prevalence of headache and depression in patients with HPD and the specific characteristics in affected individuals in comparison to patients with cardiovascular problems (CD). METHODS: Patients with HPD and CD were asked to complete a questionnaire regarding headache and depression. RESULTS: There were no significant differences between the HPD and the CD group. Prevalence of headache was not associated with the treatment modality of pituitary disease, hormone excess syndromes or any hormonal replacement therapy. However, ACTH, TSH and GH deficiency were associated with less headache when compared to patients with adequate secretion. Interestingly, patients who had prior surgery suffered significantly more often from depression. In addition, headache and depression were significantly more common in patients with microadenomas than in macroadenomas. DISCUSSION: The risk for headache and depression is mainly influenced by a combination of factors, but a specific pituitary hormone deficiency may decrease risk for headache.

A hypertensive emergency with acute visual impairment due to excessive liquorice consumption.

Hypokalaemic hypertension is the classical presentation of primary hyperaldosteronism but may also result from other mineralocorticoid activity, such as liquorice ingestion. Onset of hypertension as well as serum renin and aldosterone levels are central for the diagnosis. Liquorice ingestion has been reported to induce hypertension, hypokalaemia and metabolic alkalosis due to inhibition of the enzyme 11-ß-hydroxy steroiddehydrogenase 2. Here, we report the case of a hypertensive emergency with acute visual impairment due to hypertensive retinopathy in clear conjunction with a considerable consumption of liquorice.

[Hyponatremia: differential diagnosis and therapy]. / Hyponatriämie: Differenzialdiagnose und Therapie.

Hyponatremia is the most commonly occurring electrolyte disorder and is associated with increased morbidity and mortality­independent of the underlying disease. Despite its high prevalence, hyponatremia is often underestimated and inadequately addressed in clinical routine. Depending on disease stage and severity, the electrolyte disorder can present with a wide spectrum of neurological signs and symptoms, ranging from adynamia and gait disturbances, to syncope or coma. While the underlying causes of hyponatremia may be manifold, their identification is crucial to initiating adequate therapeutic measures for symptomatic and causal therapy. The syndrome of inappropriate antidiuretic hormone (ADH) secretion (SiADH) is the most common cause of hyponatremia, present in 1/3 of hyponatremic patients and usually a result of medication, neurological, respiratory or malignant disease. A differential diagnostic approach using a simple algorithm that includes clinical and laboratory parameters is essential for identifying the underlying cause of hyponatremia and administering goal-directed therapy. The development of vaptans has provided new options in the treatment of SiADH-associated hyponatremia.

Lack of nidogen-2 increases blood pressure, glomerular and tubulointerstitial damage in DOCA-salt hypertension.

BACKGROUND: Nidogen-2, an extracellular matrix protein, is ubiquitous in renal basement membranes linking the laminin and collagen IV networks. Nidogen-2-deficient (nidogen-2(-/-)) mice do not exhibit a phenotype, and renal basement membranes appear normal. The functional role of nidogen-2 in the adult kidney under pathological conditions however remains unclear. We tested the hypothesis that nidogen-2 mediated cell-matrix interactions are important to maintain glomerular integrity and structure in renal hyperperfusion and hypertension. MATERIALS AND METHODS: Two weeks after unilateral nephrectomy (UNX), desoxycorticosterone (DOCA)-salt hypertension was induced in nidogen-2(-/-) mice and their wild type littermates for 6 weeks. Renal damage was assessed by means of semiquantitative scoring, morphometric analysis, immunohistochemistry and measurement of serum creatinine and albumin excretion. RESULTS: UNX alone resulted in a very mild increase in renal damage in nidogen-2(-/-) mice compared to wild type animals. Following DOCA-salt treatment, blood pressure, serum creatinine and albumin excretion were significantly higher in nidogen-2(-/-) than in wild type mice. In addition, nidogen-2(-/-) mice showed increased mesangial cell hyperplasia and matrix expansion with higher expression of fibronectin and its receptor alpha8 integrin. Glomerular capillaries were significantly reduced in size and number. CONCLUSIONS: We demonstrate that in both mild and severe glomerular damage, lack of nidogen-2 is associated with: (i) increased mesangioproliferation; (ii) higher mesangial matrix expansion; and (iii) reduction in glomerular capillary supply. These findings suggest a critical role for nidogen-2 in the maintenance of glomerular structure in the diseased kidney.

[Renal lesions of paraproteinemias and fibrillary glomerulopathies]. / Nierenbefunde bei Paraproteinämien und fibrillären Glomerulopathien.

The term "paraproteinemia" or dysproteinemia" refers to a group of diseases caused by specific proteins that very often leads to kidney disease. In these cases a kidney biopsy is often the first diagnostic procedure leading to the diagnosis of a systemic disease. Due to the very variable presentation of the kidney disease in paraproteinemias a diagnosis is often very difficult without specific clinical data. Therefore, we recommend systematic investigation of the kidney biopsy including routine immunohistochemical stains for kappa- and lambda-light chains and electron microscopy in elderly patients with proteinuric kidney disease of unknown origin. In the following we will briefly discuss renal manifestations and clinical symptoms in multiple myeloma with light- or heavy chain deposition (LCDD: light chain deposition disease, HCDD: heavy chain deposition disease), macroglobulinemia Waldenström (Morbus Waldenström), primary amyloidosis or so called monoclonal gammopathy of uncertain dignity (benign monoclonal gammopathy) and fibrillary glomerulopathies.

Laser capture microdissection and real-time PCR for analysis of glomerular endothelin-1 gene expression in mesangiolysis of rat anti-Thy 1.1 and murine Habu Snake Venom glomerulonephritis.

Molecular analysis of pathologic changes in glomeruli requires methods allowing rapid and exact detection of alterations in gene expression. Here, we analyzed endothelin-1 (ET-1) mRNA expression in mesangiolytic glomeruli during the course of a rat and murine model of mesangioproliferative glomerulonephritis (GN). A novel method combining laser capture microdissection (LCM), which permits the precise removal of selected mesangiolytic glomeruli, with a highly sensitive real-time RT-PCR technique was used. Anti-Thy 1.1. GN was introduced in male Sprague-Dawley rats (1.0 mg/kg body weight of OX-7 IV) and Habu Snake Venom GN was introduced in C57BL6 mice (habu snake venom toxin 6 mg/kg body weight IV). The degree of mesangiolysis during both GNs was analyzed using a semiquantitative scoring system. Mesangiolytic glomeruli were microdissected at different days of the diseases (day 2, 6, and 12 in anti-Thy 1.1 GN and days 1, 3, 7, and 14 in Habu Snake Venom GN) and from normal control animals. After RNA extraction and cDNA synthesis, ET-1 gene expression was measured by real-time RT-PCR. In parallel, in anti-Thy 1.1. GN ET-1 mRNA expression was analyzed using semiquantitative nonradioactive in situ hybridization; ET-1 protein expression was investigated by immunohistochemistry. Mesangiolysis peaked at day 6 in anti-Thy1.1 GN and at day 1 in Habu Snake Venom GN. Mesangiolytic glomeruli were easily microdissected on cryostat sections in both models; quantification of mRNA with RT-PCR was reliable and reproducible. Glomerular ET-1 mRNA expression increased during the course of anti-Thy 1.1 GN and Habu Snake Venom GN peaked when mesangiolysis was most pronounced. This was seen by RT-PCR after glomerular LCM and by in situ hybridization; in parallel, glomerular ET-1 protein expression was increased. Combination of LCM and RT-PCR is a reliable method for quantification of localized gene expression in isolated renal structures. The above data argue for an important role of ET-1 in pathogenesis and/or repair of mesangiolysis in experimental mesangioproliferative GN.

Regulatory mechanism in glomerular mesangial cell proliferation.

Glomerular mesangial cells have a central function in maintaining structure and function of the glomerular capillary ultrafiltration apparatus. Regardless of the type of glomerular injury, imbalances in the control of mesangial cell replication appear to play a key role in the pathogenesis of progressive renal failure. The available evidence from in vitro and in vivo studies indicates that such regulatory mechanisms include specific soluble and non-soluble extracellular factors and a complex array of receptor-mediated signals which control cell proliferation, survival and apoptosis. This review summarizes results from recent investigations concerning regulation of cell cycle progression in mesangial cells. In addition to results from cell culture studies, descriptive findings on expression and regulation of cell cycle-regulatory proteins and their potential role for altered mesangial cell behaviour in glomerular disease are considered. We believe that better understanding of processes which regulate mesangial cell replication could lead to novel diagnostic as well as therapeutic strategies and, thus, help control better proliferative glomerulonephritis.