In vivo parathyroid hormone stimulates in vitro bone resorption by bovine monocytes

Cells of the monocyte-macrophage lineage have been thought to play a role in bone resorption. We examined the effects of in vivo administration of parathyroid hormone and 1,25-dihydroxyvitamin D3 on the ability of monocytes to degrade bone in vitro. Administration of parathyroid hormone for 4 d resulted in sustained hypercalcemia and a transient 1-d increase in plasma 1,25-dihydroxyvitamin D3. Parathyroid hormone significantly stimulated bone degradation by monocytes 2.6 times more than that of pretreatment controls. Parathyroid hormone treatment significantly enhanced (threefold) release of superoxide anion by monocytes stimulated with phorbol 12-myristate 13-acetate and increased migration of monocytes to bone particles in vitro. Continuous 7-d infusion of 1,25-dihydroxyvitamin D3 (50 micrograms/d) elevated plasma 1,25-dihydroxyvitamin D3 until infusions were discontinued. Increased 1,25-dihydroxyvitamin D3 was associated with hypercalcemia, which continued for several days postinfusion. In vivo administration of 1,25-dihydroxyvitamin D3 did not affect in vitro ability of monocytes to degrade bone. We concluded that in vivo administration of parathyroid hormone enhanced in vitro responsiveness of isolated monocytes in a manner consistent with a role for monocytes in bone remodeling. Furthermore, these data suggested that circulating monocytes could be a useful experimental model for further studies on parathyroid hormone responsiveness and bone resorption for the cow with milk fever.     

Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression

Converging evidence points to hypofunction of the left prefrontal cortex in depression. Repetitive transcranial magnetic stimulation (rTMS) activates neurons near the surface of the brain. We questioned whether daily left prefrontal rTMS might improve mood in depressed subjects and report a pilot study of such treatment in six highly medication-resistant depressed inpatients. Depression scores significantly improved for the group as a whole (Hamilton Depression Scores decreased from 23.8 +/- 4.2 (s.d.) at baseline to 17.5 +/- 8.4 after treatment; t = 3.03, 5DF, p = 0.02, two-tailed paired t-test). Two subjects showed robust mood improvement which occurred progressively over the course of several weeks. In one subject, depression symptoms completely remitted for the first time in 3 years. Daily left prefrontal rTMS appears to be safe, well tolerated and may alleviate depression.     

Transition from fetal to extrauterine circulation

In utero, there is increased pulmonary vascular resistance favoring minimal pulmonary blood flow and right-to-left shunting of blood through the ductus arteriosus and foramen ovale. Delivery initiates a series of complex biochemical and structural changes whereby the neonate assumes those processes critical to survival. This article reviews fetal circulation, the characteristics of the fetal cardiopulmonary system, and the transition from fetal to neonatal circulation. It also discusses the consequences of disrupted transition to extrauterine life and the relationship between fetal cardiopulmonary anatomy and congenital heart disease.     

School-screening for scoliosis. A prospective epidemiological study in northwestern and central Greece

A two-year prospective study was done to assess the prevalence and distribution of various parameters associated with scoliosis in schoolchildren in northwestern and central Greece. A total of 82,901 children (41,939 boys and 40,962 girls) who were nine to fourteen years old were screened for scoliosis. Five thousand eight hundred and three children had clinical signs of scoliosis and, of these, 4185 were referred for posteroanterior radiographs (to be made with the patient standing) because they had a positive result on the forward-bending test (a difference of more than five millimeters between the two sides of the torso as measured in the thoracic or thoracolumbar region with use of a ruler and a level plane) at the time of a second screening. The prevalence of scoliosis (defined as a curve of 10 degrees or more) was 1.7 per cent (1436 of 82,901 children), and most of the curves (1255; prevalence, 1.5 per cent) were small (10 to 19 degrees). The ratio of boys to girls was 1:2.1 over-all but varied according to the magnitude of the curve (1:1.5 for curves of less than 10 degrees, 1:2.7 for curves of 10 to 19 degrees, 1:7.5 for curves of 20 to 29 degrees, 1:5.5 for curves of 30 to 39 degrees, and 1:1.2 for curves of 40 degrees or more). Thoracolumbar curves were the most common type of curve identified, followed by lumbar curves; specifically, of the 1436 children who had a curve of at least 10 degrees, 493 (34.3 per cent) had a thoracolumbar curve, 475 (33.1 per cent) had a lumbar curve, 261 (18.2 per cent) had a thoracic curve, and 207 (14.4 per cent) had a double curve. Although most (753) of these curves were to the left, the left:right ratio varied according to the location of the apex of the curve (1:3.1 for thoracic curves, 2.0:1 for thoracolumbar curves, and 3.2:1 for lumbar curves). The cost of the screening process was negligible (estimated at thirty cents per child); however, the decreased number of operative procedures performed in children from the geographical area of our University Hospital, the identification of a large number of previously undiagnosed curves (eleven of which were treated operatively and 170 of which were treated with a brace), and the identification of children who were at high risk for progression were considered important benefits of the school-screening program.     

Expression of the Solfolobus acidocaldarius Rieske iron sulfur protein II (SOXF) with the correctly inserted [2FE-2S] cluster in Escherichia coli

The Rieske protein II (Schmidt et al., 1996, FEBS Lett. 388, 43-46) from the thermoacidophilic crenarcheon Sulfolobus acidocaldarius (DSM 639) was expressed in E. coli cells. The full length protein was strictly bound to the E. coli membranes and could only be removed by detergent treatment indicating the presence of a membrane anchor. The iron sulfur cluster was correctly inserted into a fraction of the full length protein and much more effectively into a soluble form created by the deletion of the 45 N-terminal amino acids. The soluble form of the protein displayed the typical spectroscopic properties of a respiratory Rieske protein. The midpoint potential was +375 mV determined by CD redox potentiometry. The presented data demonstrate that the structure of the recombinant protein is very similar or identical to the authentic protein making this a powerful model system for the studies of Rieske proteins by site directed mutagenesis.     

Human leukocyte interferon-alpha in a hydrophilic cream versus in a gel for the treatment of genital herpes in males: a placebo-controlled, double-blind, comparative study

The aim of this double-blind, placebo-controlled, comparative study was to differentiate the clinical efficacy and tolerability of human leukocyte interferon-alpha incorporated (2 x 10(6) IU/g) in a hydrophilic cream and in a gel to heal males afflicted with first episodes of genital herpes. Patients (n = 60), aged 18-40 years (mean 23.2) with culture-confirmed diagnosis of herpes genitalis were randomized to three parallel groups. Each patient was allocated a precoded 40-g tube, containing either preparation or placebo. Cream or gel was applied three times daily for 5 consecutive days. The duration of the active treatment was two weeks. Patients were examined after 48 hours in initial treatment, and thereafter two times a week. A reepithelialized lesion with some residual erythema was recorded as healed. The study demonstrated that patients treated with leukocyte interferon-alpha cream had both significantly shorter mean duration of lesions than gel and placebo recipients (5.3 days vs. 8 days, 13 days respectively; p < 0.001) and a higher number of healed patients (80% vs. 55%, 20% respectively; p < 0.001). Of the 60 patients, 49 (82%) complained of no drug-related side effects. Eleven patients predominantly in the cream/gel groups reported non-objective transitory increase in their body temperature (> 38 degrees C) with moderate headache, malaise and myalgia. The study was followed-up for 24 months after the first day of the treatment, and out of 31/60 cured patients, 4 had a relapse after 18 months. In conclusion the study affirmed that human leukocyte interferon-alpha (2 x 10(6) IU/g) in a hydrophilic cream is more efficacious than its incorporation in gel or placebo, thus suggesting that leukocyte interferon-alpha in a hydrophilic cream, with a profile of non-objective mild to moderate drug-induced indications, may be considered an alternative and effective treatment modality to cure male patients afflicted with first episodes of genital herpes.     

Evidence for a third component in neutrophil aggregation: potential roles of O-linked glycoproteins as L-selectin counter-structures

The homotypic aggregation of neutrophils requires the participation of L-selectin and the beta 2-integrins, but it has not been clear whether the two receptors recognize one another as counter-structures or whether other adhesion molecules are involved. We have examined aggregation of live neutrophils with target populations, manipulated to alter expression of adhesive epitopes, using flow cytometry. A target population depleted of both L-selectin and activatable beta 2-integrin displayed an ability to aggregate with live neutrophils, suggesting that these two molecules are not counter-structures. We also found that an O-sialoglycoprotease (GCP) from Pasteurella haemolytica is capable of inhibiting homotypic aggregation. Neutrophils treated with GCP lose O-glycosylated proteins but retain L-selectin and activatable beta 2-integrin. One or more of the GCP substrates appears to function in L-selectin-dependent binding but not in beta 2-integrin-dependent binding. Together the data suggest a mechanism of aggregation that is analogous to leukocyte-endothelial cell adhesion in which a low-affinity carbohydrate-dependent interaction precedes a high-affinity integrin-dependent adhesion.