Postsynaptic effects of alpha agonists on adrenoceptors of the reserpinized rat vas deferens

The activities of the alpha-1 antagonist prazosin and alpha-2 antagonist yohimbine were evaluated against noradrenaline (NA), methoxamine (Me) and clonidine (Clo) on the reserpinized rat vas deferens. Prazosin antagonized competitively Me but not NA and Clo. On the other hand yohimbine showed a low and not competitive antagonism towards all the three agonists. Similar results were obtained when the antagonistic activities were tested in the presence of the alternative antagonist, in the attempt to isolate a single receptor population. We can conclude that the smooth musculature of the rat vas deferens contains prevalently alpha-1 adrenoceptors and a small population of NA activated receptors resistant to alpha-2 antagonists.     

Sex steroids and odorants modulate gonadotropin-releasing hormone secretion in primary cultures of human olfactory cells

Olfactory neurons and GnRH neurons share a common origin during development. In the nasal epithelia, GnRH neurons persist throughout fetal life and adulthood. The fate and function of these neurons in vivo have remained unknown. In a previous in vitro study, we isolated, cloned, and propagated primary long term cell cultures from the olfactory neuroepithelium of 8- to 12-week-old human fetuses. These cells expressed both neural proteins as well as olfactory genes and were responsive to odorant stimuli. We now report that these human olfactory cells also express the GnRH gene and protein. Combined HPLC and RIA studies have indicated that these cells release authentic GnRH in spent media. The release of GnRH was time dependent and was positively affected by sex steroids and odorants. Immunohistochemical data demonstrated the presence of sex steroid receptors in these cells. The presence of the alpha- and beta-subtypes of the estrogen receptor was also demonstrated by RT-PCR and Western blot analysis. When the cells were stimulated with increasing concentrations of 17beta-estradiol in the presence of a fixed concentration of progesterone (10(-7) mol/L), the combination of the two steroids induced a 3- to 4-fold increase in GnRH secretion. This stimulatory effect was completely blunted by tamoxifen. Neither 17beta-estradiol nor progesterone was effective when tested separately. Treatment with increasing concentrations of the odorant, l-carvone, induced a time- and dose-dependent dramatic increase in GnRH protein release (1000-fold increase) and gene expression. Repeated application of the stimulus resulted in a progressive lower responsiveness of the cells. To our knowledge, this is the first time that primary cell cultures from human fetal olfactory neuroepithelium have been shown to express and release GnRH. Our results also demonstrate that these cultures, which are sensitive to sex steroids and odorants, can be useful models in the study of the complex array of regulatory factors that finely tune GnRH secretion in humans.     

Long-term outcome in diabetic heart failure patients treated with cardiac resynchronization therapy

BACKGROUND: Diabetes mellitus is an independent risk factor for increased morbidity and mortality in heart failure (HF) patients. AIMS: To compare functional and structural improvement, as well as long-term outcome, between diabetic and non-diabetic HF patients treated with cardiac resynchronization therapy (CRT). METHODS: We compared response to CRT in 141 diabetic and 214 non-diabetic consecutive patients. Major events were; death from any cause, urgent heart transplantation and implantation of a left ventricular (LV) assist device. Frequencies of hospitalisation and defibrillator (CRT-D) discharges were also analyzed. RESULTS: CRT was able to significantly improve functional capacity, ventricular geometry and neurohumoral imbalance in both diabetic and non-diabetic patients over a median follow-up time of 34 months. Overall event-free survival was similar in diabetic and non-diabetic patients (HR 1.23, p=0.363), as was survival free from CRT-D interventions (HR 1.72; p=0.115) and hospitalisations (HR 1.12; p=0.500). On multivariable analysis, NYHA class IV (p=0.002), low LV ejection fraction (p=0.002), absence of beta-blocker therapy (p<0.001), impaired renal function (p=0.003), presence of an epicardial lead (p=0.025), but not diabetes (p=0.821) were associated with a poor outcome after CRT. CONCLUSIONS: Diabetic HF patients treated with CRT had a very favourable functional and survival outcome, which was comparable to non-diabetic patients.     

Effect of hypertonic saline treatment on the inflammatory response after hydrochloric acid-induced lung injury in pigs

OBJECTIVES:

Hypertonic saline has been proposed to modulate the inflammatory cascade in certain experimental conditions, including pulmonary inflammation caused by inhaled gastric contents. The present study aimed to assess the potential anti-inflammatory effects of administering a single intravenous dose of 7.5% hypertonic saline in an experimental model of acute lung injury induced by hydrochloric acid.

METHODS:

Thirty-two pigs were anesthetized and randomly allocated into the following four groups: Sham, which received anesthesia and were observed; HS, which received intravenous 7.5% hypertonic saline solution (4 ml/kg); acute lung injury, which were subjected to acute lung injury with intratracheal hydrochloric acid; and acute lung injury + hypertonic saline, which were subjected to acute lung injury with hydrochloric acid and treated with hypertonic saline. Hemodynamic and ventilatory parameters were recorded over four hours. Subsequently, bronchoalveolar lavage samples were collected at the end of the observation period to measure cytokine levels using an oxidative burst analysis, and lung tissue was collected for a histological analysis.

RESULTS:

Hydrochloric acid instillation caused marked changes in respiratory mechanics as well as blood gas and lung parenchyma parameters. Despite the absence of a significant difference between the acute lung injury and acute lung injury + hypertonic saline groups, the acute lung injury animals presented higher neutrophil and tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage analysis. The histopathological analysis revealed pulmonary edema, congestion and alveolar collapse in both groups; however, the differences between groups were not significant. Despite the lower cytokine and neutrophil levels observed in the acute lung injury + hypertonic saline group, significant differences were not observed among the treated and non-treated groups.

CONCLUSIONS:

Hypertonic saline infusion after intratracheal hydrochloric acid instillation does not have an effect on inflammatory biomarkers or respiratory gas exchange.     

Is posterior percutaneous screw-rod instrumentation a safe and effective alternative approach to TLSO rigid bracing for single-level pyogenic spondylodiscitis? Results of a retrospective cohort analysis

Background contextCurrently, treatment for patients diagnosed with noncomplicated (ie, known infectious agent, no neurologic compromise, and preserved spinal stability) pyogenic spondylodiscitis (PS) is based on intravenous antibiotics and rigid brace immobilization. Since January 2010, we started offering our patients percutaneous posterior screw-rod instrumentation as an alternative approach to rigid bracing. Supposed benefits of posterior percutaneous instrumentation over rigid bracing are earlier free mobilization, increased comfort, and faster recovery.PurposeTo evaluate safety and effectiveness of posterior percutaneous spinal instrumentation for single-level PS and compare clinical and quality-of-life outcomes with standard thoracolumbosacral orthosis (TLSO) rigid bracing.Study design/SettingRetrospective observational cohort study.Patient sampleTwenty-seven patients consecutively diagnosed with single-level noncomplicated lower thoracic or lumbar PS from January 2010 to December 2011.Outcome measuresHealing rate, healing time, and changes in segmental kyphosis Cobb angle were compared in the two treatment groups. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complete blood count at regular time points until complete healing were also obtained. Self-report measures included Visual Analog Scale (VAS), Short-Form 12 (SF-12), and EuroQol five-dimension (EQ-5D) questionnaires.MethodsAt enrollment, patients were offered to choose between 24/7 TLSO rigid bracing for 3 to 4 months and bridging posterior percutaneous screw-rod instrumentation followed by soft bracing for 4 weeks after surgery. All patients underwent antibiotic therapy accordingly to isolated infectious agents. Patients were seen in the clinic at 1, 3, 6, and 9 months, and ESR, CRP, complete blood count, VAS, SF-12, and EQ-5D questionnaires were obtained. Segmental kyphosis was measured at diagnosis and at 9 months follow-up. Two-way repeated-measures analysis of variance was used to assess group and time differences across time points.ResultsFifteen patients chose conservative treatment, whereas 12 patients chose surgical treatment. Complete infection healing was achieved in all patients with no significant differences in healing time (p<.366). C-reactive protein and ESR levels decreased in both groups accordingly with positive response to therapy with no significant differences. Surgically treated patients had significantly lower VAS scores at 1 month (2.76±0.80 vs. 5.20±1.21, p<.001) and 3 months (2.31±0.54 vs. 2.85±0.54, p<.016) post-diagnosis over TLSO patients. Moreover, surgery patients also showed steeper and statistically significant improvements in SF-12 scores over TLSO patients at 1, 3, and 6 months post-diagnosis (p<.012); no significant differences were detected at the other time points. EuroQol five-dimension index was significantly higher in surgery patients at 1 month (0.764±0.043 vs. 0.458±0.197, p<.001) and 3 months (0.890±0.116 vs. 0.688±0.142, p<.001); no significant changes were observed in segmental pre- and posttreatment kyphosis between the two groups. No instrumentation-related complications were observed in any patient.ConclusionsPosterior percutaneous spinal instrumentation is a safe, feasible, and effective procedure in relieving pain, preventing deformity, and neurologic compromise in patients affected by noncomplicated lower thoracic (T9–T12) or lumbar PS. Posterior instrumentation did not offer any advantage in healing time over TLSO rigid bracing because infection clearance is strongly dependent on proper antibiotic therapy. Nevertheless, surgical stabilization was associated with faster recovery, lower pain scores, and improved quality of life compared with TLSO conservative treatment at 1, 3, and 6 months after treatment.     

Comparison of 3 self lubrificated urethral catheters: prospective study on 27 patients

Clean intermittent catheterization has become a usual procedure in urologic practice. Self lubrificated catheters are nowadays accepted as the most efficient. This randomised and prospective study compared tolerance and efficiency in a group of 27 patients of three well known catheters (12 charriere, straight): Flocath (Ruschcare), Lofric (Astratech) and Easycath (Coloplast). The systematic comparison of this three catheters did not allow to put in a prominent position one of these. The three catheters are extremely close in terms of tolerance and performance.     

An interdisciplinary approach to the design of new structures active at the beta-adrenergic receptor. Aliphatic oxime ether derivatives

On the basis of results previously obtained from structural and theoretical studies on beta-adrenergic drugs, a series of aliphatic oxime ether derivatives (AOEDs) was synthesized. As expected, pharmacological in vitro tests showed that compounds examined exhibit a marked and competitive antagonism at beta-adrenoceptors; the beta 2/beta 1 selectivity ratio indicated that they are more active on the tracheal than on the cardiac beta-receptor. The chemical reactivity of the AOEDs was studied through the calculation of the electrostatic molecular potential (EMP) on a model compound in its preferred conformation. The results showed that the EMP trend agrees with that previously calculated for other beta-blocking drugs.