Identification of α1-adrenoceptor subtypes in the dog prostate

Summary The ₁-adrenoceptor subtypes of dog prostate were characterized in binding and functional experiments. In saturation experiments, [³H]prazosin bound to ₁-adrenoceptors with high affinity. In the displacement experiments, unlabelled prazosin and WB4101 biphasically inhibited the binding of 400 pM [³H]prazosin, suggesting the presence of at least two distinct affinity sites for prazosin or WB4101. The proportion of high-affinity sites was approximately 10%. HV723 also recognized two distinct affinity sites but the proportion of high-affinity sites was approximately 20%. From these results the presence of three distinct ₁-adrenoceptor subtypes was suggested: presumably subtypes _1A (high affinity for prazosin and WB4101), _1N (high affinity for only HV723) and _1L (low affinity for the three antagonists) according to the recently proposed ₁-adrenoceptor subclassification. The density of subtype _1L was much higher than that of subtypes _1A and _1N subtypes. In the functional experiments, prazosin, WB4101 and HV723 competitively antagonized the contractile response to noradrenaline with low affinities close to those estimated for the _1L subtypes. These results suggest that the contractile response to noradrenaline in the dog prostate is mediated predominantly through _1L subtype -adrenoceptors.     

Does adenosine release taurine in the A1-receptor-rich hippocampus?

Purpose. To determine whether taurine would be protective in the hippocampus (rich in A1 receptors but devoid of the A2 receptor effector adenylate cyclase, which mediates the release of taurine) by determining whether taurine is released by adenosine in the non-ischemic hippocampus. Methods. Microdialysis of probes, inserted stereotactically into the bilateral hippocampi of five nonischemic brains of anesthetized rabbits and combined with high-performance liquid chromatography, was used to evaluate the effects of adenosine on taurine concentration in the interstitial fluid. Results. Sequential increase of the dialytic artificial cerebrospinal fluid concentration of adenosine (to 1 × 10⁻⁴ M, 5 × 10⁻⁴ M, 1 × 10⁻³ M, 5 × 10⁻³ M, and 1 × 10⁻² M) linearly and significantly (P < 0.0001) increased taurine concentration in the interstitial fluid. Conclusion. Adenosine delivered by microdialysis into the interstitial fluid of nonischemic rabbit hippocampus induces release of taurine in a dose-dependent manner, suggesting involvement of additional mechanisms besides the already known A2-receptor-induced release. Taurine can be anticipated to have protective effects in the hippocampus as well. Received for publication on January 19, 1998; accepted on December 9, 1998     

Differences in the expression of SSTR1–5 in meningiomas and its therapeutic potential

Beyond microsurgical resection and radiation therapy, there are currently no established treatment alternatives for meningioma patients. In selected cases, peptide radio receptor therapy (PRRT) can be implemented. For this purpose, a radionuclide is bound to a substance targeting specific receptors in meningiomas. One of them is somatostatin receptor 2, which can be found in most meningiomas. However, other somatostatin receptors (SSTR) exist, but their expressions have only been described in small case series. In this study, we analyzed the expression of SSTR1, 2A, 3, 4, and 5 in a large cohort of meningiomas in order to enable further refinement of this innovative treatment option. Overall, 726 tumor samples were processed into tissue microarrays and stained for SSTR1, 2A, 3, 4, and 5 immunohistochemically. Microscopic evaluation was done with an established semiquantitative score regarding percentual quantification and staining intensity, and results were correlated with clinical data. There was a significant lower rate of SSTR1 expression in meningiomas of male patients. Older age was associated with higher expression of SSTR1, 2A, and 5 and lower scores for SSTR3 and 4. Tumors treated with radiotherapy before resection showed lower rates of SSTR1 and 5 expression, while recurrent meningiomas had lower SSTR1 scores. Tumor tissue from patients suffering from neurofibromatosis type 2 had lower expression scores for SSTR1, 2, and 5. For SSTR3 and 4, NF2 patients showed higher scores than sporadic tumors. Spinal meningiomas had higher scores for SSTR1, 4, and 5 compared tumor location of the skull base and convexity/falx. Overall, higher WHO grade was associated with lower SSTR scores. While all SSTRs were expressed, there are marked differences of SSTR expression between meningioma subgroups. This has the potential to drive the development of more selective PRRT substances with higher treatment efficacy.

     

Potential Role of α1-Adrenoceptors in the Aetiology of LUTS

It has been assumed that α₁-adrenoceptors contribute to the aetiology of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) mainly by increasing bladder outlet resistance due to an increase in the tone of prostatic smooth muscle. This paper reviews recent evidence that α₁-adrenoceptors can also contribute to BPH by affecting prostatic growth and additionally can contribute to LUTS by effects on the bladder and the spinal cord. While direct effects on prostatic smooth muscle and hence on voiding symptoms occur via α_1A-adrenoceptors, α_1D-adrenoceptors appear to contribute to effects on bladder and spinal cord and hence storage symptoms. In contrast α_1B-adrenoceptors do not appear to be involved in lower urinary tract function but may contribute to side effects of drugs used in LUTS treatment.     

Improved epidural analgesia in the parturient in the 30° tilt position

PURPOSE: To compare the incidence of incomplete analgesia when epidural local anesthetic is administered with the parturient supine in a 30 degree leftward tilt or in the left lateral decubitus position. METHODS: After placement of a multiorifice catheter 5 cm into the epidural space, 293 women in active labour were randomly positioned either to the left lateral decubitus position (lateral group) or supine with a 30 degree leftward tilt (tilt group) and then received 13 mL bupivacaine 0.25%. The success of the epidural block was determined by asking the patient if she required additional medication 15 min later. The incidence of complications (fetal heart rate decelerations, hypotension, and ephedrine usage) was noted. RESULTS: In the lateral group, 38% required additional medication compared with 24% in the tilt group (P = 0.006). There were no differences between groups in the incidence of maternal hypotension or fetal heart rate decelerations, but more women (10%) received ephedrine in the lateral than in the tilt group (4%), P = 0.035. CONCLUSIONS: Placing the parturient supine with a 30 degree leftward tilt is associated with a greater success rate of labour epidural analgesia without an increase in complications than in women in the left lateral decubitus position. This advantage should be considered when positioning the parturient after epidural catheter placement.     

Kellgren & Lawrence grade 1 osteophytes in the knee--doubtful or definite?

The most universally accepted methods of classification of radiographic osteoarthritis (OA) is the Kellgren & Lawrence (K&L) grading system. However, there have been many criticisms of this including the grading of a doubtful osteophyte as a grade 1. We report the natural history of a given prevalent grade 1 osteophyte in a 10-year follow-up knee study. 62% of women graded at baseline with a doubtful osteophyte went on to develop true osteophytic knee OA compared with only 22% of controls with no sign of disease. So called 'doubtful' osteophytes appear to be 'real' and significantly related to OA knee and therefore cannot be ignored or classified as normal.     

In vitro and in vivo studies on the importance of the soluble guanylyl cyclase α1 subunit in penile erection

Purpose  

Soluble guanylyl cyclase (sGC), which plays a pivotal role in penile erection, is a heterodimer build up by an α and a β subunit. For both subunits two isoforms have been characterized, but only the sGCα₁β₁ and sGCα₂β₁ isoforms seem to be functionally active. To elucidate the functional role of the sGCα₁β₁ heterodimer in the mechanism of erection, experiments were performed in vivo and on isolated corpora cavernosa (CC) using sGCα₁^−/− mice.     

Can the increase in body mass index explain the rising trend in asthma in children?

BACKGROUND: The reported association between asthma and obesity and the documented rise in each over time have led to suggestions that rising obesity might explain the increase in the prevalence of asthma. Trends in both in British children participating in the National Study of Health and Growth were marked from 1982 to 1994. METHODS: Odd ratios for trends in asthma and symptoms in 8 and 9 year old children were calculated with and without adjustment for body mass index (BMI). RESULTS: In a representative sample of white children the odds ratio per year for asthma was 1.09 (95% CI 1.07 to 1.11) before and after adjustment for BMI for boys and 1.09 (95% CI 1.07 to 1.12) and 1.09 (95% CI 1.05 to 1.12), respectively, for girls. Unadjusted and adjusted odds ratios were also virtually identical for wheeze and "asthma or bronchitis". The lack of effect of adjustment was due to a change in the association between BMI and symptoms with time. CONCLUSIONS: Trends in overweight and obesity do not explain the increase in asthma. The evidence points towards the association between asthma and obesity being of recent origin. This may be explained by obesity being a marker of recent lifestyle differences now associated with both asthma and overweight.     

What's new in the use of MRI in the orthopaedic trauma patient?

MRI has been established as an essential tool for accurate diagnosis in patients with musculoskeletal trauma. Its major advantages include excellent soft tissue contrast, high spatial resolution and lack of ionizing radiation. Although plain radiographs remain the basic tool for diagnosis and treatment planning in bone fractures assisted by CT in pelvic, spine and large joints injuries, there are specific circumstances that require MRI. For instance, tendinous, ligamentous, intraarticular structures such as the cartilage and menisci, and intramedullary injury are seen mostly with MRI. Volumetric 3D techniques are now commercially available and provide higher spatial resolution which improves anatomic detail, allows multiplanar reformations and reduces the acquisition time. Newer applications on quantitative rather than morphologic imaging, such as relaxometry and diffusion tensor imaging, may be of paramount importance in treatment planning in the near future. Software improvements reduce metal induced artefacts, allowing thus imaging of the postoperative patient with metallic implants. A tendency towards a structured reporting pattern and standardised medical communication needs to be further explored for the benefit of orthopaedic surgeons, radiologists and patients.     

Foreign body in the heart

As an emergency, a foreign body in the heart should generally be removed as early as possible by surgical or non-surgical procedures in order to avoid any complications. Early treatment typically results in a better prognosis.CASE REPORTA38-year old woman…     

Neurosurgery in the himalayas…

The health scenario of western Nepal is bleak and especially the Neurosurgical facilities are poor. We started the Department of Neurosurgery in April 2008 and has been improvising to do various cases with good success rate. Although not very well equipped, we have tried to do our best and the results have been encouraging.