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Biomedical subjects

M Ludwig

Publications and source records attributed to M Ludwig.

At least 91 records · Page 5Linked to original sources

Taurine selectively modulates the secretory activity of vasopressin neurons in conscious rats.

Previous experiments have shown that a 10-min forced swimming session triggers the release of vasopressin from somata and dendrites, but not axon terminals, of neurons of the hypothalamic-neurohypophysial system. To further investigate regulatory mechanisms underlying this dissociated release, we forced male Wistar rats to swim in warm (20 degrees C) water and monitored release of the potentially inhibitory amino acids gamma amino butyric acid (GABA) and taurine into the hypothalamic supraoptic nucleus using microdialysis. Forced swimming caused a significant increase in the release of taurine (up to 350%; P < 0.05 vs. prestress release), but not GABA. To reveal the physiological significance of centrally released taurine, the specific taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide was administered into the supraoptic nucleus via retrodialysis. Administration of this antagonist caused a significant increase in the release of vasopressin within the supraoptic nucleus and into the blood both under basal conditions and during stress (up to 800%; P < 0.05 vs. basal values), without affecting hypothalamic or plasma oxytocin. Local administration of the GABA(A) receptor antagonist bicuculline, in contrast, failed to influence vasopressin secretion at either time point. In a separate series of in vivo electrophysiological experiments, administration of the same dosage of the taurine antagonist into the supraoptic nucleus via microdialysis resulted in an increased electrical activity of identified vasopressinergic, but not oxytocinergic, neurons. Taken together our data demonstrate that taurine is released within the supraoptic nucleus during physical/emotional stress. Furthermore, at the level of the supraoptic nucleus, taurine inhibits not only the electrical activity of vasopressin neurons but also acts as an inhibitor of both central and peripheral vasopressin secretion during different physiological states.

Action Potentials↗

The role of gonadotropin-releasing hormone antagonists in in vitro fertilization.

Gonadotropin-releasing hormone (GnRH)-antagonists can suppress the pituitary hormone secretion completely within a few hours, allowing the avoidance of premature luteinization within controlled ovarian hyperstimulation (COH) for assisted reproductive technologies (ART) by midcycle administration. Two different protocols were described, which were widely used in COH in several phase II and III studies as well as in clinical practice since the GnRH-antagonists Cetrorelix (Cetrotidesound recording copyright sign; Serono International S.A., Geneva, Switzerland) and Ganirelix (Orgalutansound recording copyright sign, Antagonsound recording copyright sign; Organon, Oss, The Netherlands) are available on the market. Cetrorelix was applied in single- and multiple-dose protocols; Ganirelix was used until now only according to the multiple-dose protocol. Fertilization rates of >60% as well as clinical pregnancy rates of about 30% per transfer sound most promising. Estradiol secretion is not compromised by the GnRH-antagonists using recombinant follicle-stimulating hormone (FSH) for COH. The incidence of a premature leutinizing hormone (LH) surge is far below 2% while the pituitary response remains preserved, allowing the induction of ovulation by GnRH or GnRH-agonists. However, luteal phase support remains mandatory. The incidence of severe ovarian hyperstimulation syndrome (OHSS) seems to be lower under antagonist treatment than in the long agonistic protocol. Treatment time is significantly shortened. Without any doubt GnRH-antagonists have the potential to become the new standard for controlled ovarian hyperstimulation.

Embryo Transfer↗

Uterine artery Doppler velocimetry and the outcome of pregnancies resulting from ICSI.

BACKGROUND: An increased incidence of pregnancy complications following assisted reproduction has been reported. The use of uterine artery Doppler ultrasound may aid the prediction of such complications. METHODS: Doppler was performed at 18-24 weeks gestation in 114 singleton and 32 twin pregnancies after intracytoplasmic sperm injection (ICSI) and compared with a control group matched for age, parity and plurality. Outcome variables included gestational age at delivery, prematurity, preterm premature rupture of membrane (PPROM), birth weight, birth weight discordance of >20% in twins, small for gestational age (SGA), mode of delivery, development of pre-eclampsia and placental abruption. RESULTS: Compared with the controls, there were no significant differences concerning uterine Doppler parameters, pregnancy complications and the neonatal outcome, either in singleton or in twin pregnancies. According to Doppler results and/or risk factors by medical history, 42% of singleton ICSI and 39% of spontaneous singleton pregnancies were considered as high risk. In singletons, abnormal Doppler findings were associated with pre-eclampsia in 22% and SGA in 26% of ICSI patients, compared with 33 and 21% in controls; in contrast, 0 and 10% in ICSI and 3 and 6% in controls showed these complications but no risk factors respectively. No correlation was found between PPROM, prematurity, the rate of Caesarean section and pathological Doppler results. CONCLUSIONS: Uterine Doppler examination holds the potential to identify patients with an increased risk for developing pregnancy complications. According to our results, this risk is not elevated after ICSI treatment, therefore the decision of offering an intensified antenatal care should be based on the results of Doppler examination or risks by medical history rather than the mode of conception.

Abruptio Placentae↗

Recent developments in diagnosis and therapy of the prostatitis syndromes.

Chronic pelvic pain syndromes, including prostatitis, remain a difficult clinical entity in terms of diagnosis and treatment to both urologists and patients. This review attempts to highlight the most recent developments and advances in the field of chronic pelvic pain syndromes in terms of prevalence, aetiology, pathogenesis, diagnosis, and current approaches to treatment.

Humans↗

NO inhibits supraoptic oxytocin and vasopressin neurons via activation of GABAergic synaptic inputs.

To study modulatory actions of nitric oxide (NO) on GABAergic synaptic activity in hypothalamic magnocellular neurons in the supraoptic nucleus (SON), in vitro and in vivo electrophysiological recordings were obtained from identified oxytocin and vasopressin neurons. Whole cell patch-clamp recordings were obtained in vitro from immunochemically identified oxytocin and vasopressin neurons. GABAergic synaptic activity was assessed in vitro by measuring GABA(A) miniature inhibitory postsynaptic currents (mIPSCs). The NO donor and precursor sodium nitroprusside (SNP) and L-arginine, respectively, increased the frequency and amplitude of GABA(A) mIPSCs in both cell types (P < or = 0.001). Retrodialysis of SNP (50 mM) onto the SON in vivo inhibited the activity of both neuronal types (P < or = 0.002), an effect that was reduced by retrodialysis of the GABA(A)-receptor antagonist bicuculline (2 mM, P < or = 0.001). Neurons activated by intravenous infusion of 2 M NaCl were still strongly inhibited by SNP. These results suggest that NO inhibition of neuronal excitability in oxytocin and vasopressin neurons involves pre- and postsynaptic potentiation of GABAergic synaptic activity in the SON.

Animals↗

Immunocytological analysis of leukocyte subpopulations in urine specimens before and after prostatic massage.

OBJECTIVE: To evaluate the presence of leukocyte subpopulations in urine after prostatic massage (VB 3) in symptomatic patients with > or =10 leukocytes/high power field (magnification x1,000) in expressed prostatic secretions, and who were classified as suffering from chronic bacterial prostatitis or inflammatory chronic pelvic pain syndrome. METHODS: 115 consecutive patients were investigated. Granulocytes in centrifuged midstream urine (VB 2) and VB 3 were counted after Papanicolaou stain. Macrophages, B and T lymphocytes were analyzed after immunocytological staining with monoclonal antibodies according to the alkaline phosphatase anti-alkaline phosphatase method. The counts were quantified as the number of cells per view field at a magnification of x400. In all patients, acute or chronic urethritis had been excluded before enrollment in the study. 16 men without signs or symptoms of urogenital inflammation served as controls. RESULTS: Of the 115 patients, 101 men demonstrated > or =10 leukocytes/view field in VB 3. In comparison to VB 2, the leukocyte subpopulations in VB 3 demonstrated an increase in granulocytes (9.2-fold), macrophages (7.6-fold), T lymphocytes (7.6-fold), and B lymphocytes (4-fold). The increase was statistically significant (p<0.001 each). The proportion of these cells in VB 3 was 81.6, 11.1, 5.5, and 1.8%, respectively. As compared to controls, all leukocyte subsets in VB 3 were significantly elevated (p>0.001 each). CONCLUSION: Elevated numbers of leukocytes in VB 3 are indicative of prostatitis provided that urethral inflammation and leukocyturia in VB 2 are excluded. Granulocytes are the predominant cell type of inflammation. The increase in macrophages, T and B lymphocytes in prostatic secretions indicate the participation of both the cellular and humoral immune system in the inflammatory process.

Adult↗

Prospective, randomized study to evaluate the success rates using hCG, vaginal progesterone or a combination of both for luteal phase support.

BACKGROUND: A prospective study was done to compare the efficacy of luteal phase support (LPS) using either three times hCG (group I, n=77), hCG on the day of embryo transfer (ET) in combination with daily vaginal progesterone (group II, n=62) or vaginal progesterone only (group III, n=70). METHOD: All patients were treated using the long luteal protocol for controlled ovarian stimulation in an IVF (in vitro fertilization) cycle. Patients were randomized to one of these groups when estradiol was <2500 pg/ml and less than 12 oocytes were retrieved (low risk groups). If estradiol was > or = 2500 pg/ml and/or at least 12 oocytes were retrieved (high risk groups), patients were randomized to receive either hCG in combination with daily vaginal progesterone (group IV, n=83) or progesterone only (group V, n=121). For vaginal progesterone Utrogest was used (three times daily two capsules containing 100 mg progesterone, 600 mg/d). RESULTS: Demographic data were comparable within the high risk and low risk groups. However, for unknown reasons the fertilization rate was significantly higher in group V (48%) compared to group IV (40%) (p<0.05), leading to a significantly higher cumulative embryo score. There were no statistically significant differences with regard to the main outcome parameter, the clinical ongoing pregnancy rate in the low risk groups (14.3%, 14.5%, 11.4%) and the high risk groups (21.0%, 21.5%), respectively. Using a standardized discomfort scale, there were more complaints towards the end of the luteal phase in the groups receiving hCG only or an additional injection of hCG, when compared to the progesterone only groups. CONCLUSION: Progesterone only for luteal phase support leads to the same clinical ongoing pregnancy rate as hCG, but has no impact on the comfort of the patient.

Administration, Intravaginal↗

Crystal structures of two polymorphs of Ca3[Al2N4].

Green transparent single crystals of alpha-Ca3[Al2N4] (monoclinic, P2(1)/c, No. 14, a = 957.2(3) pm, b = 580.2(3) pm, c = 956.3(5) pm, beta = 111.62(3) degrees; Z = 4) were obtained from reactions of mixtures of the representative metals with nitrogen above temperatures of 1000 degrees C. beta-Ca3[Al2N4] (monoclinic, C2/c, No. 15, a = 1060.6(2) pm, b = 826.0(2) pm, c = 551.7(1) pm, beta = 92.1(1) degrees; Z = 4) was formed as a byproduct of a reaction of calcium with alumina under nitrogen at T = 930 degrees C in form of colorless crystals. The crystal structures of the two polymorphs contain edge- and corner-sharing AlN4 tetrahedra, leading to different layered anionic partial structures: infinity 2[AlN2/2N2/3)2(AlNN2/2N1/3)6/3(12-)] in the alpha-phase and infinity 2[Al2N2N4/2(6-)] in the beta-polymorph.

Journal Article↗

Evaluation of the cytokines interleukin 8 and epithelial neutrophil activating peptide 78 as indicators of inflammation in prostatic secretions.

OBJECTIVES: Chronic prostatitis/chronic pelvic pain syndrome (CPPS) is a disorder characterized by pelvic pain and varying degrees of inflammation exhibited in expressed prostatic secretions (EPS). To provide objective parameters of inflammation, we measured the cytokines interleukin 8 (IL-8) and epithelial neutrophil activating peptide 78 (ENA-78) in EPS of healthy men, men with benign prostatic hyperplasia (BPH), men with bacterial prostatitis (BP), and men with chronic prostatitis/CPPS. METHODS: Enzyme-linked immunosorbent assays of the EPS for IL-8 and ENA-78 were done in 63 men: control (n = 9), BPH (n = 6), BP (n = 3), inflammatory CPPS (National Institutes of Health [NIH] category IIIa) (n = 17), noninflammatory CPPS (NIH category IIIb) (n = 17), and asymptomatic inflammatory prostatitis (NIH category IV) (n = 11). RESULTS: IL-8 was detectable in all patients, and ENA-78 was detectable in all except 2 patients (threshold of detection 10 pg/mL for IL-8, 15 pg/mL for ENA-78). Mean levels of IL-8 [ENA-78] were similar in control (3010 pg/mL [423 pg/mL]), BPH (3341 pg/mL [98 pg/mL]), and IIIb (2751 pg/mL [335 pg/mL]) groups. Both cytokine levels were higher in BP (11,175 pg/mL [13,761 pg/mL]), IIIa (10,418 pg/mL [2240 pg/mL]), and IV (8571 pg/mL [1865 pg/mL]) groups. A statistically significant difference between the control group versus BP, IIIa, and IV (P <0.05) groups was found for IL-8 but not for ENA-78. CONCLUSIONS: IL-8 and ENA-78 are frequently elevated in the EPS of men with BP, CPPS IIIa, and asymptomatic inflammatory prostatitis category IV. These cytokines are direct mediators of leukocyte accumulation and activation at inflammatory sites and may be responsible, in part, for the presence of inflammatory reaction in the prostate.

Adult↗

Nitric oxide and the oxytocin system in pregnancy.

We examined the functional role of the nitric oxide (NO)-producing system in magnocellular neurons and how this changes at the end of pregnancy, using a combination of blood sampling and oxytocin radioimmunoassay, electrophysiology, immunocytochemistry for Fos expression, and in situ hybridization histochemistry. In urethane-anesthetized virgin rats, systemic administration of NO synthase (NOS) inhibitors led to a facilitation of oxytocin release evoked by hyperosmotic stimulation. Direct application of the NO donor sodium nitroprusside to the supraoptic nucleus by in vivo microdialysis inhibited the electrical activity of both oxytocin neurons and vasopressin neurons, whereas direct application of an NOS inhibitor increased electrical activity, indicating that endogenous NO acts within the supraoptic nucleus to inhibit neuronal activity. However, during late pregnancy, the influence of endogenous NO is dramatically downregulated, reflected by a reduced expression of neuronal NOS mRNA in these neurons and a loss of efficacy of NOS inhibitors on stimulus-evoked oxytocin release. This downregulation may cause the oxytocin system to become more excitable at term, resulting in the capacity for greater release of oxytocin during parturition.

Animals↗

Clinical application of GnRH-antagonists.

Due to the different pharmacological mode of action, GnRH-antagonists seem to open up new avenues to hormonal treatment in several indications. Although it may be still too early to speculate about the possible end of the era of GnRH-agonists, from what is known today, the advantages of GnRH-antagonists are most evident in our opinion. When the development of sustained delivery systems may continue and be completed, the antagonists will have a major potential within benign gynecological conditions and also in the treatment of malignancies such as prostatic, mammary, endometrial or ovarian cancer. Suitable sustained delivery systems and the development of GnRH-antagonists with sufficient oral bioavailability, represent the present and future challenge for these efforts.

Clinical Trials, Phase III as Topic↗

GABAergic projection from the arcuate nucleus to the supraoptic nucleus in the rat.

Electrical stimulation of the neurones in the hypothalamic arcuate nucleus results in a transient inhibition followed by a marked post-stimulus excitation of magnocellular neurones of the supraoptic nucleus. Microdialysis administration of the gamma-aminobutyric acid agonist (GABA(A)), muscimol, directly into the supraoptic nucleus inhibited both oxytocin and vasopressin neurones and these actions were fully reversed by the GABA(A) antagonist bicuculline. In addition, bicuculline administration blocked the inhibition induced by arcuate stimulation, but had no effect on the post-stimulus excitation. Thus, part of the inhibitory pathway arising from or passing through the arcuate nucleus to the supraoptic nucleus is mediated by the neurotransmitter GABA. However, the post-inhibitory excitation induced by arcuate stimulation is not a rebound response, but appears to involve an independent excitatory pathway.

Animals↗

The situation of preimplantation genetic diagnosis in Germany: legal and ethical problems.

Preimplantation genetic diagnosis (PGD) has not been performed in Germany. Existing German laws do not explicitly permit or prohibit PGD. German law does forbid the wasting of totipotent embryonic cells, fertilizing oocyctes without transferring them in the same cycle, and the use of micromanipulations that later may harm embryonic development. German law also limits the number of oocytes allowed to be fertilized in each in vitro fertilization (IVF) cycle to three and prohibits research on embryos. The existence of these laws may impede but not prevent the development of PGD programmes in Germany. In contrast, the liberal regulation of pregnancy termination coupled with the development of ethical guidelines specific to PGD may facilitate the introduction of PGD in Germany. Because of these contradictions, legislation is required to clarify the legal status of PGD in Germany.

Abortion, Legal↗

Significant reduction of the incidence of ovarian hyperstimulation syndrome (OHSS) by using the LHRH antagonist Cetrorelix (Cetrotide) in controlled ovarian stimulation for assisted reproduction.

A prospective, randomized study was performed to compare the efficiency of hormonal stimulation for IVF (in vitro fertilization) in either the long luteal protocol, using the LHRH agonist Buserelin, or the multiple dose LHRH antagonist protocol, using the LHRH antagonist Cetrorelix. Here we present the data on the incidence of ovarian hyperstimulation syndromes (OHSS). 85 and 188 patients were recruited for the stimulation in the LHRH agonist and in the LHRH antagonist protocol, respectively. The groups were comparable regarding anamnestic data. The incidence of WHO degrees II and degrees III OHSS was significantly lower in the Cetrorelix than in the Buserelin group (1.1% vs. 6.5%, p=0.03). Additionally 3 patients in the Cetrorelix group (1.6%) and 5 patients in the Buserelin group (5.9%) did not receive hCG because of a threatening OHSS. The follicle maturation was more homogeneous in the Cetrorelix protocol, with less small follicles on the day of hCG administration but a similar number of oocyte cumulus complexes retrieved. The pregnancy rates per cycle were not significantly different in the Cetrorelix and Buserelin protocol (22% vs. 26%). The Cetrorelix multiple dose protocol is advantageous compared to the long protocol regarding the incidence of OHSS, a potentially life threatening complication of controlled ovarian stimulation.

Buserelin↗

Serum leptin concentrations throughout the menstrual cycle.

Leptin is a cytokine involved in the regulation of food intake and fertility in rodents and in humans. No data exist about serum leptin serum levels during the spontaneous menstrual cycle. In this study 16 ovulatory cycles of endocrinologically normal volunteers were analyzed. Blood samples were taken on alternate days throughout the menstrual cycle for measurement of serum estradiol, progesterone, LH, FSH and leptin serum levels. No correlation of leptin values with estradiol values (r = 0.07) or progesterone values (r = 0.14) were seen. Mean leptin values during the luteal phase were significantly higher (16.67 +/- 9.45 ng/mL) compared to the follicular phase (13.50 +/- 8.75 ng/mL) (P < 0.02). A strongly positive correlation with the progression of the menstrual cycle could be seen (r = 0.91). The physiological significance of higher luteal phase leptin levels is unknown.

Adult↗

Deep vein thrombosis during administration of HMG for ovarian stimulation.

We report a case of activated protein C (APC) resistance and deep calf vein thrombosis under controlled ovarian stimulation for in vitro fertilization. The thrombosis occurred before administration of human chorionic gonadotrophin for ovulation induction on the 8th day of hMG (human menopausal gonadotrophin). The patient was stimulated according to the long luteal protocol. Cases of arterial and venous thrombosis as a result of ovarian stimulations are reviewed.

Activated Protein C Resistance↗