Involvement of D1 dopamine receptors in the control of TSH secretion in the male rat

The effects of SCH 23390 (D1 dopamine receptor antagonist), SK&F 38393 (D1 dopamine receptor agonist), raclopride and remoxipride (D2 dopamine receptor antagonists) and ketanserin (5-hydroxytryptamine 2 receptor antagonist) on TSH serum levels (radioimmunoassay) and on brain catecholamine levels (Falck-Hillarp methodology in combination with quantitative histofluorimetry) were studied. SCH 23390 produced a dose-dependent increase in serum TSH levels in the lower dose range (0.01-0.03 mg kg-1, i.p.) administered 30 min before decapitation and in the higher dose range (1.0-3.0 mg kg-1) when given 2 h before decapitation. Following 30 min of treatment with the high doses of SCH 23390, reductions in serum TSH levels were found. The changes observed following SCH 23390 treatment occurred without affecting catecholamine levels in the median eminence and the peri- and paraventricular hypothalamic regions. Raclopride (0.1-10 mg kg-1, i.p.), remoxipride (1.0 mg kg-1, i.p.) or ketanserin (0.3 mg kg-1, i.p.) changed neither serum TSH levels nor brain catecholamine levels, SK&F 38393 (1.0-10 mg kg-1, i.p.) produced an increase in serum TSH levels. The results suggest the existence of inhibitory and facilitatory mechanisms regulating TSH secretion mediated via D1 dopamine receptors.     

Screw angulation affects bone-screw stresses and bone graft load sharing in anterior cervical corpectomy fusion with a rigid screw-plate construct: a finite element model study

Background contextAnterior corpectomy and reconstruction with bone graft and a rigid screw-plate construct is an established procedure for treatment of cervical neural compression. Despite its reliability in relieving symptoms, there is a high rate of construct failure, especially in multilevel cases.PurposeThere has been no study evaluating the biomechanical effects of screw angulation on construct stability; this study investigates the C4–C7 construct stability and load-sharing properties among varying screw angulations in a rigid plate-screw construct.Study designA finite element model of a two-level cervical corpectomy with static anterior cervical plate.MethodsA three-dimensional finite element (FE) model of an intact C3–T1 segment was developed and validated. From this intact model, a fusion model (two-level [C5, C6] anterior corpectomy) was developed and validated. After corpectomy, allograft interbody fusion with a rigid anterior screw-plate construct was created from C4 to C7. Five additional FE models were developed from the fusion model corresponding to five different combinations of screw angulations within the vertebral bodies (C4, C7): (0°, 0°), (5°, 5°), (10°, 10°), (15°, 15°), and (15°, 0°). The fifth fusion model was termed as a hybrid fusion model.ResultsThe stability of a two-level corpectomy reconstruction is not dependent on the position of the screws. Despite the locked screw-plate interface, some degree of load sharing is transmitted to the graft. The load seen by the graft and the shear stress at the bone-screw junction is dependent on the angle of the screws with respect to the end plate. Higher stresses are seen at more divergent angles, particularly at the lower level of the construct.ConclusionThis study suggests that screw divergence from the end plates not only increases load transmission to the graft but also predisposes the screws to higher shear forces after corpectomy reconstruction. In particular, the inferior screw demonstrated larger stress than the upper-level screws. In the proposed hybrid fusion model, lower stresses on the bone graft, end plates, and bone-screw interface were recorded, inferring lower construct failure (end-plate fractures and screw pullout) potential at the inferior construct end.     

HER-2/neu (c-erbB-2) evaluation in primary breast carcinoma by fluorescent in situ hybridization and immunohistochemistry with special focus on intratumor heterogeneity and comparison of invasive and in situ components.

We have studied the intratumor HER-2/neu heterogeneity in 78 consecutive and population-based primary invasive breast carcinomas. Within the invasive component, heterogeneity was detected in only 1 of 78 tumors. In 48 tumors (62%), we found both in situ and invasive components in analyzed tissue sections. Twelve of these 48 tumors had a difference of at least 2 arbitrary units in the in situ compared with the invasive part of the tumor with regard to the HER-2/neu status analyzed by HercepTest (immunohistochemistry). Eight of these 12 tumors were reanalyzed with fluorescent in situ hybridization and immunohistochemistry with and without a new Automated Cellular Imaging System. In this limited material, immunohistochemistry in combination with the Automated Cellular Imaging System seemed to have a better correlation with fluorescent in situ hybridization than immunostaining analyzed manually. In conclusion, HER-2/neu expression is not seldom heterogeneous in invasive compared with in situ components within a tumor. This finding should be considered in the choice of evaluation method. To avoid heterogeneity as a confounding factor in HER-2/neu analyses, detection methods such as immunohistochemistry and fluorescent in situ hybridization, which can provide evaluation in a preserved tissue architecture, should be used. Perhaps the intratumor HER-2/neu heterogeneity can explain some of the unexpected failures of trastuzumab therapy.     

No evidence for an altered mRNA expression or protein level of haematopoietic cell phosphatase in CD34+ bone marrow progenitor cells or mature peripheral blood cells in polycythaemia vera

Abstract: Polycythaemia vera (PV) is a myeloproliferative disorder characterized by haematopoietic progenitor cells being hypersensitive to cytokines such as erythropoietin, interleukin-3, stem cell factor and insulin-like growth factor 1, which results in an increased production of mature blood cells. The pathogenetic cellular mechanism(s) behind this hypersensitivity to cytokines is unknown, but the number of cytokine receptors and the interaction between ligand and receptor are normal in PV. Interest has therefore focused on post-receptor mechanism(s). Haematopoietic cell phosphatase (HCP) is an intracellular tyrosine phosphatase that has been demonstrated to regulate proliferative signals negatively induced by the cytokines mentioned above. Moreover, motheaten mice that genetically lack HCP have an increased amount of erythroid progenitors that are hypersensitive to Epo, and patients with familial polycythaemia have been shown to exhibit a mutation of the Epo receptor gene that includes the docking site for HCP. We therefore studied mRNA expression of HCP in pure populations of CD34⁺ cells, granulocytes, platelets and lymphocytes from patients with PV, chronic myeloid leukaemia (CML) or essential thrombocythemia (ET), as well as healthy controls. Using a polymerase chain reaction analysis employing specific primers for HCP, we failed to detect any abnormalities of HCP expression in PV in any of the cell populations that were examined. Moreover, HCP mRNA expression was similar in ET and CML compared to controls. Finally, Western blot analysis revealed a normal HCP protein content in PV granulocytes and platelets. We therefore conclude that neither an impaired expression of the HCP gene nor a defect in HCP protein synthesis is present in PV, and does not seem to play a role in the aetiology of this disorder.     

Effect of inositol hexaphosphate on retention of zinc and calcium from the human colon

Colonic retention of zinc and calcium was studied after installation during colonoscopy in 11 patients of a solution of 30 mumol zinc, 6.4 mmol calcium and 500 mumol inositol hexaphosphate (phytic acid) labelled with 65Zn and 47Ca. Whole-body retention of the radionuclide at day 13 was 1.0 +/- 1.0 per cent (mean +/- s.d.) for zinc and 4.0 +/- 2.9 per cent for calcium. The retention of zinc but not of calcium was lower than observed earlier under similar conditions from a solution not containing phytic acid and indicates formation of an indigestible complex between phytic acid and zinc. Addition of amino acids to the solution in 3 subjects did not seem to affect the retention of zinc and calcium.     

Country-specific cost-effectiveness of early intervention with budesonide in mild asthma.

Early intervention with budesonide is an effective strategy for mild persistent asthma, which has been shown to provide additional clinical benefits at a low incremental cost using USA cost data. The present authors analysed whether this strategy would be cost-effective using cost data for other countries. Based on the 3-yr prospective, randomised, double-blind inhaled Steroid Treatment As Regular Therapy (START) in early asthma study (comparing budesonide and placebo combined with usual asthma therapy), the cost-effectiveness was estimated separately for eight different countries, from both healthcare payer and societal perspectives, of adding budesonide to usual asthma therapy. Local unit costs were applied to data for the total trial population. Incremental cost-effectiveness ratios (ICER) were estimated as cost per symptom-free day (SFD) gained. Budesonide increased SFDs by an average of 14.1 days annually. From a healthcare payer perspective, budesonide would reduce the total cost of asthma care in Australia. In Sweden, Canada, France, Spain, UK, China and the USA, the ICER ranged from US$2.4-11.3 per SFD. From a societal perspective, budesonide would be cost-saving in Australia, Canada and Sweden. In conclusion, for countries where costs with budesonide are higher, the policy implication has to be determined by that health system's willingness to pay for an additional symptom-free day. However, where budesonide therapy increases symptom-free days and reduces total costs, the policy conclusion clearly favours early intervention.     

Effect of Seminal Plasma Fractions on Stallion Sperm Survival after Cooled Storage

This study aimed to evaluate stallion sperm survival after 24 h of cooled storage in the presence of seminal plasma (SP) derived from the sperm‐rich fractions (SRF) or sperm‐poor fractions(SPF) of the ejaculate, without SP, or in the presence of SP from other stallions. Ejaculates were collected from four stallions using an automated phantom, which separated the semen into five cups. Centrifuged and washed spermatozoa from cup 2 (SRF) were mixed with skim milk extender to a concentration of 100 × 10⁶ sperm/ml and then 1:1 (v/v) with SP from the stallion's own or another stallions’ second (SP‐SRF) or last cup (SP‐SPF). Skim milk extender (K) and skim milk extender supplemented with modified Tyrode's medium (KMT) were used as control treatments. After a 24‐h storage period in a transport container, spermatozoa were evaluated for motion characteristics and plasma membrane integrity by calcein acetoxymethyl (AM)/propidium iodide staining. The percentage of spermatozoa with intact plasma membranes after storage was lower in SP‐SRF than in SP‐SPF, and the highest in K (P < 0.05). Progressive motility (PMOT) was lower for sperm stored in SP‐SRF than for sperm stored in SP‐SPF (P < 0.05), but there was no significant difference in total motility (TMOT). Sperm stored in KMT (P < 0.05) registered the highest TMOT and PMOT percentages. Osmolarity was significantly higher and pH lower in K than in KMT or SP. Treatment with SP‐SPF from three stallions benefited the PMOT of sperm from one stallion. These preliminary findings suggest that SP from SRFs may be more harmful during storage than SP from SPFs. Removal of SP improves sperm survival in KMT extender, and exchanging SP between stallions seems to influence sperm survival.     

Healing-in of root analogue titanium implants placed in extraction sockets. An experimental study in the beagle dog.

The aim of these animal experiments was to characterize and evaluate the healing-in of root analogue titanium implants fitting with high precision to the alveolar wall. Four beagle dogs were used in the study. The roots of the 3rd and 4th mandibular premolars in both quadrants of 3 dogs and in 1 quadrant of 1 dog (dog 4) were extracted after hemisection. Each root was machine-copied to 1 titanium analogue. In dog 4, however, 2 titanium analogues were fabricated from each of the 4 extracted roots. This enabled insertion of analogues also into the contralateral sockets obtained by extraction of the corresponding roots immediately before implant installation, which was undertaken 2 weeks after the first extractions. Thus, in all, 32 analogues were implanted in their respective (or contralateral) sockets following ridge incision and elevation of mucoperiosteal flaps. The analogues were carefully covered by the repositioned flaps. In dog 4, 2 analogues from the immediate sockets and 2 from the 2-week sockets were surgically exposed and supplied with titanium crowns after a healing period of 2 months. The healing after implantation was evaluated by clinical, radiographic and histological measures after 2, 12 or 36 months. Two analogues (6%) were lost due to early (during the 1st week) exposure to the oral cavity. Another 2 analogues (6%) were, although not exposed, encapsulated by soft tissue and were easily removed with a surgical forceps. Twenty-eight analogues (88%) were healed-in by contact between bone and implant (osseointegration).(ABSTRACT TRUNCATED AT 250 WORDS)