Calcitonin gene-related peptide immunreaktive Nervenfasern in der Dura mater encephali der Ratte

In this paper morphological and physiological experiments are described that refer to the concept of neurogenic inflammation of meningeal structures as a putative source of migrainous pain and other headaches. The main emphasis of this study carried out on the duramater encephali of the rat was the functional role of calcitonin generelated peptide (CGRP), a vasodilatory neuropeptide of fine afferent nerve fibres. Immunocytochemical preparations showed that the parietal dura mater was densely innervated by CGRP immunoreactive nerve fibres, the distribution and ultrastructure of which were examined by ligh and electron microscopy. The dense innervation around the medial meningeal artery suggested a vasomotor function of these peptidergic fibres. In further experiments the CGRP immune product of the nerve fibres could be diminished by electrical stimulation of the dura mater. Extracellular recordings from trigeminal ganglion cells showed that electrical and mechanical stimulation of large dural vessels activate trigeminal afferents. In a final series of experiments the dural blood flow around branches of the medial meningeal artery was measured with a laser Doppler flowmeter. The blood flow was increased by electrical stimulation of the dura, the size of this effect depending on stimulus strength and frequency. This increase was inhibited in a dose-dependent manner by the competitive CGRP antagonist CGRP(8-37), which shows an involvement of CGRP in the regulation of meningeal blood flow. We conclude that stimulation of trigeminal afferents innervating the dura mater releases CGRP from peptidergic afferent terminals, thereby causing vasodilatation and increasing the meningeal blood flow, an important component of neurogenic inflammation. The preparation decribed will be used for further studies on basic mechanisms of neurogenic inflammation and nociception in meningeal structures.     

傅青主保产无忧散的临床应用进展

为了解傅青主保产无忧散的临床应用情况，本文从傅青主保产无忧散的起源、药理作用、临床研究等方面对保产无忧散进行梳理分析，发现保产无忧散有养血、益气、理气的作用。临床上具有防治难产，治疗多种原因导致的先兆流产、早产，可将晚期妊娠臀位、横位转为头位以利于阴道分娩，对过期妊娠有一定的催引产效果，对于妊娠期特发性黄疸、肝功能异常等妊娠期并发症有防治作用，还可用于治疗胃脘痛，配合针刺促卵泡发育治疗女性不孕症，值得进一步研究。     

Ghrelin does not mediate the somatotroph and corticotroph responses to the stimulatory effect of glucagon or insulin-induced hypoglycaemia in humans

OBJECTIVE: Acylated ghrelin, a gastric peptide, possesses a potent GH- but also significant ACTH/cortisol-releasing activity mediated by the activation of GH secretagogue receptors (GHS-R) at the hypothalamus-pituitary level. The physiological role of ghrelin in the control of somatotroph and corticotroph function is, however, largely unclear. Glucagon is known to induce a clear increase of GH, ACTH and cortisol levels in humans, at least after intramuscular administration. In fact, glucagon is considered to be a classical alternative to insulin-induced hypoglycaemia (ITT) for the combined evaluation of the function of GH and the hypothalamus-pituitary-adrenal (HPA) axis. We aimed to clarify whether ghrelin mediate the GH and corticotroph responses to intramuscular glucagon or ITT, which has recently been reported able to induce a surprising ghrelin decrease. SUBJECTS: To this aim we enrolled six normal young male subjects [age (mean +/- SD): 29.0 +/- 8.0 years, body mass index (BMI) 21.9 +/- 2.5 kg/m(2)]. DESIGN AND MEASUREMENTS: In all the subjects we studied ghrelin, GH, ACTH, cortisol and glucose levels after glucagon (GLU; 0.017 mg/kg intramuscularly), ITT (0.1 IU/kg insulin intravenously) or saline administration. RESULTS: Saline infusion was not followed by any significant variation in ghrelin, GH and glucose levels while ACTH and cortisol showed the expected spontaneous morning trend toward a decrease. GLU administration increased (P < 0.01) circulating GH, ACTH and cortisol as well as insulin and glucose levels. ITT induced an obvious increase (P < 0.01) of GH, ACTH and cortisol levels. The ITT-induced increases in GH and ACTH, but not cortisol, levels were higher (P < 0.01) than those after GLU. Circulating ghrelin levels were not modified by GLU. On the other hand, ghrelin levels underwent a transient reduction (P < 0.01) after insulin-induced hypoglycaemia. CONCLUSIONS: Ghrelin does not mediate the GH and ACTH responses to glucagon or to the ITT. In fact, ghrelin levels are not modified at all by glucagon and transiently decrease during the ITT. These findings support the assumption that ghrelin does not play a major role in the physiological control of somatotroph and corticotroph function.     

Safety of long-term interruption of successful antiretroviral therapy: the ATHENA cohort study

We studied the dynamics of CD4 cell counts after the interruption of virologically successful highly active antiretroviral therapy (HAART) in 139 patients. Changes in CD4 cell counts during HAART interruption followed a biphasic pattern: an initial rapid decline during the first month followed by a slow decrease. During 48 weeks of follow-up mean CD4 cell counts remained just above the mean pre-HAART level. This limits the feasibility of structured treatment interruptions for patients with low nadir CD4 cell counts.     

Comparing the effect of positioning on cerebral autoregulation during radical prostatectomy: a prospective observational study

Journal of Clinical Monitoring and Computing - Surgery in the prolonged extreme Trendelenburg position may lead to elevated intracranial pressure and compromise cerebral hemodynamic regulation. We...     

Brentuximab vedotin as salvage treatment in Hodgkin lymphoma naïve transplant patients or failing ASCT: the real life experience of Rete Ematologica Pugliese (REP)

Brentuximab vedotin (BV) shows a high overall response rate (ORR) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) after autologous transplant (ASCT). The aim of this multicenter study, conducted in nine Hematology Departments of Rete Ematologica Pugliese, was to retrospectively evaluate the efficacy and safety of BV as salvage therapy and as bridge regimen to ASCT or allogeneic transplant (alloSCT) in R/R HL patients. Seventy patients received BV. Forty-five patients (64%) were treated with BV as bridge to transplant:16 (23%) patients as bridge to ASCT and 29 (41%) as bridge to alloSCT. Twenty-five patients (36%), not eligible for transplant, received BV as salvage treatment. The ORR was 59% (CR 26%). The ORR in transplant naïve patients was 75% (CR 31%). In patients treated with BV as bridge to alloSCT, the ORR was 62% (CR 24%). In a multivariate analysis, the ORR was lower in refractory patients (p?<?0.005). The 2y-OS was 70%. The median PFS was 17 months. Ten of the 16 (63%) naïve-transplant patients received ASCT, with 50% in CR before ASCT. In the 29 patients treated with BV as bridge to alloSCT, 28 (97%) proceeded to alloSCT with 25% in CR prior to alloSCT. The most common adverse events were peripheral neuropathy (50%), neutropenia (29%) and anemia (12%). These data suggest that BV is well tolerated and very effective in R/R HL, producing a substantial level of CR. BV may also be a key therapeutic agent to achieve good disease control before transplant, improving post- transplant outcomes, also in refractory and heavily pretreated patients, without significant overlapping toxicities with prior therapies.     

Association study of IRAK-M and SIGIRR genes with SLE in a large European-descent population

Objective: The aim of this study was to evaluate the relevance of genetic variants of interleukin receptor-associated kinase-M (IRAK-M) (rs11465955, rs1624395, rs1152888 and rs1370128) and single immunoglobulin IL1-1R-related molecule (SIGIRR) (rs3210908) genes in systemic lupus erythematosus (SLE) in four independent European-descent populations. Methods: Our study population consisted of a total of 2033 SLE patients and 2357 healthy controls from Spain, Germany, Italy and Argentina. The genotyping was performed using a polymerase chain reaction (PCR) system with pre-developed TaqMan allelic discrimination assay. Genetic association between the genotyped markers was determined by PLINK v1.07. Results: After a meta-analysis including these four populations, a trend of association between rs11465955 (P(meta) (-analysis) =?0.06), rs1370128 (P(meta) (-analysis) =?0.07) and rs1624395 (P(meta) (-analysis) =?0.06) polymorphisms was found. However, these differences did not reach statistical significance. In addition, we did not find any association between SLE and the rs1152888 IRAK-M (P(meta) (-analysis) =?0.13) and the rs3210908 SIGIRR (P(meta) (-analysis) =?0.40) polymorphisms after the meta-analysis. No evidence of association with IRAK-M haplotypes was found. Conclusion: These results suggest that the tested variations of IRAK-M and SIGIRR genes do not confer a relevant role in the susceptibility to SLE in European-descent populations.