The effect of surface chemistry modification of titanium alloy on signalling pathways in human osteoblasts

Establishing and maintaining mature bone at the bone–device interface is critical to the long-term success of prosthesis. Poor cell adhesion to orthopaedic and dental implants results in implant failure. Considerable effort has been devoted to alter the surface characteristics of these biomaterials in order to improve the initial interlocking of the device and skeleton. We investigated the effect of surface chemistry modification of titanium alloy (Ti–6Al–4V) with zinc, magnesium or alkoxide-derived hydroxy carbonate apatite (CHAP) on the regulation of key intracellular signalling proteins in human bone-derived cells (HBDC) cultured on these modified Ti–6Al–4V surfaces. Western blotting demonstrated that modifying Ti–6Al–4V with CHAP or Mg results in modulation of key intracellular signalling proteins. We showed an enhanced activation of Shc, a common point of integration between integrins and the Ras/Mapkinase pathway. Mapkinase pathway was also upregulated, suggesting its role in mediating osteoblastic cell interactions with biomaterials. The signalling pathway involving c-fos (member of the activated protein-1) was also shown to be upregulated in osteoblasts cultured on the Mg and CHAP modified Ti–6Al–4V. Thus surface modification with CHAP or Mg may contribute to successful osteoblast function and differentiation at the skeletal tissue–device interface.     

A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor

The renin-angiotensin system (RAS) is essential for blood pressure control and water-electrolyte balance. Until the discovery of the renin receptor, renin was believed to be mainly a circulating enzyme with a unique function, the cleavage of angiotensinogen. We report a unique mutation in the renin receptor gene (ATP6AP2) present in patients with X-linked mental retardation and epilepsy (OMIM no. 300423), but absent in 1200 control X-chromosomes. A silent mutation (c.321C>T, p.D107D) residing in a putative exonic splicing enhancer site resulted in inefficient inclusion of exon 4 in 50% of renin receptor mRNA, as demonstrated by quantitative RT-PCR. Analysis of membrane associated-receptor molecular forms showed the presence of full-length and truncated proteins in the patient. Functional analysis demonstrated that the mutated receptor could bind renin and increase renin catalytic activity, similar to the wild-type receptor, but resulted in a modest and reproducible impairment of ERK1/2 activation. Thus, our findings confirm the importance of the RAS in cognitive processes and indicate a novel specific role for the renin receptor in cognitive functions and brain development.     

Detecting depressive disorders in drug abusers : A comparison of screening instruments

Previous investigators have reported a high prevalence of depressive symptoms in drug-dependent patients. Given the responsiveness of depressive disorders to both psychological and pharmacological treatments, it is desirable to find an economical, efficient screening instrument to detect depressive disorders in this population. In this study, 6 depression symptom screening scales (Beck Depression Inventory, Hamilton Depression Scale, Raskin Depression Scale, Degree of Illness Rating, Symptom Checklist 90 Overall, and Depression Subscale) based on either clinician interview or patient self report, were compared according to their utility in detecting cases of depression among 64 applicants for treatment at a substance abuse treatment unit of a community mental health center. The criteria for a case of depression were the Research Diagnostic Criteria (RDC) which are specified and operationalized. Cases identified using previously described cutoff scores on the screening scales were compared to rates based on the RDC and sensitivity and specificity were determined. The results showed that: (1) although the sensitivity of the symptom scales was applicable, ranging from 65--94%, the specificity was less impressive, ranging from 39--61%, and (2) the Beck Depression Inventory, a 13-item patient self report was the most sensitive and specific and is recommended for screening drug-dependent populations for depression.     

Sensitivity to hymenoptera in adult males

The authors studied the sera of 86 selected adult male office workers for IgE antibodies to yellow jacket and honey bee venoms and to environmental inhalants and foods. Structured histories provide information about the experiences of these men with the Hymenoptera and other immunological information. Three men (3%) gave a history of a local or general reaction to the Hymenoptera but no antibodies were detected. Ten men (12%) had IgE antibodies to yellow jacket or honey bee venoms but none gave a history of a reaction. Nine of these men were atopic. The authors speculate that IgE antibodies to the Hymenoptera in atopic adult males may be more common than is currently recognized.     

SKIN POTENTIAL, HEART RATE, AND THE SPAN OF IMMEDIATE MEMORY

Relations between orienting response and span of immediate memory were studied by measuring skin potential responses (SPR) and heart rate (HR). Four conditions were studied by presenting letters in a tachistoscope and a 1000 cycle, 100 db tone simultaneous on some but not all trials. The conditions (15 Ss in each) were: tone and letters for 10 trials, then letters alone for 10 trials; tone and letters for 20 trials; only letters for 10 trials, followed by letters and tone for 10 trials; and only letters for 20 trials. The results showed: (1) positive SPR habituated and negative did not, (2) tone produced more SP activity, (3) HR showed a shift from acceleration to deceleration over 20 trials, but tone had no influence, (4) tone had no direct influence on span scores, (5) Ss showed improvement in number ol letters reported correctly. There was a significant correlation between span and negative SPR when tone was sounded (r =. 36).     

A cooling system for prostaglandin infusions

A simple system has been developed-for the prolonged infusion of an iced solution of prostacyclin (PGI₂). In a 24 h period at pH 10, there is a theoretical loss in activity of 6%, while a 5 h infusion leads to a 2% reduction in activity. The stability of the cooling system was demonstrated in six dog experiments where mean arterial pressure (MAP) was reduced to 58±3.8 Torr (x±SEM) over a 5 h period of infusing 500 ng/kg/min. In a saline medium, at 3°C, a 5 h PGI₂ infusion led to a stable reduction in MAP, whereas, at a temperature of 24°C, a 70 loss of infusate activity was noted. Supported in part by The National Institute of Health, Grant No. GM24891-04; The U.S. Army Medical Research and Development Command, Contract No. DAMD17-78-C-8026; The Brigham Surgical Group, Inc., and The Trauma Research Foundation.     

Systematic investigations on the reactivity of oxazolinium salts

The termination reaction of the cationic polymerization of 2-phenyl- and 2-nonyl-2-oxazolines was examined by reacting the corresponding model oxazolinium salts having tosylate and trifluoromethansulfonate counterions with various nucleophiles. The reaction was monitored by ¹H NMR spectroscopy. Piperidine and KOH react with the oxazolinium salts very fast and quantitatively. In the case of piperidine, the use of a double molar amount of piperidine is necessary to achieve complete conversion. The addition of piperidine, pyridine, 4-dimethylaminopyridine and morpholine takes place in position 5 of the oxazolinium ring, whereas water and KOH add in position 2. The rate of the termination reaction depends on the electron density of the nucleophile which can be correlated with the pK_a value. With CF₃SO as counterion the addition of nucleophiles in position 5 is distinctly faster, whereas the addition of water in position 2 is much slower than with TsO^? as counterion. The ring-opening of the nonyl oxazolinium ion is slower than that of the phenyl oxazolinium ion.