Effects of baclofen and phaclofen on receptive field properties of rat whisker barrel neurons

Extracellular single-unit recordings were made in somatosensory cortical barrels of fentanyl-sedated rats. Whiskers were deflected singly or in paired combinations. lontophoretically-applied (−)-baclofen disproportionately reduced weak responses, and phaclofen disproportionately increased them, resulting in more tightly focused or more broadly focused receptive fields, respectively. Both drugs had only minor effects on surround inhibition. In light of previous findings, we conclude that GABA_A and GABA_B mechanisms both act to enhance spatial contrast, but that the former plays a much greater role in enhancing temporal resolution.     

Retrospective multicenter analysis of 3i endosseous dental implants placed over a five‐year period

Osseointegrated dental implants have now become an accepted form of treatment for patients with a fully or partially missing dentition. The purpose of this study was to evaluate the performance of 3i threaded and cylindrical implants. During a 5-year period, a total of 1969 3i endosseous implants were placed at 6 centers in the United States and 2 elsewhere in the edentulous and partially edentulous jaws of 653 consecutive patients ranging in age from 18 to 82 years. Of the total number of implants placed, 1341 were commercially pure titanium threaded implants and 628 were titanium plasma-sprayed implants with a cylindrical configuration. A total of 28 patients with 110 implants were lost to follow-up. Implants in these patients were considered neither a success nor a failure. Success was predicated on the osseointegration of each and every implant followed in this analysis rather than the persistence of prosthetic function. Confirmed bone anchorage was considered essential for success. A total of 625 patients with 1871 implants remain in the study with a follow-up period ranging from 6 to 60 months. A total of 93 implants (5.0% of the total implants followed) were considered as failures. A mean implant survival rate was 95.0% for both the threaded and the cylindrical implant was calculated. The success rate of threaded implants was 97.0% in the mandible and 93.8% in the maxilla. The success rate for the 3.3mm cylindrical implants was 96.0% in the mandible and 95.5% in the maxilla, and the success rate of 4.0mm diameter cylindrical implants was 95% in the mandible and 92.0% in the maxilla. Causes of failure consisted of loss of osseointegration 2.3%crestal bone loss requiring periodontal therapy after the first year of function 1.7% and mechanical problems associated with the prosthesis 0.9%. This retrospective analysis of the 3i endosseous implant system is comparable to previous reports on other implant systems in terms of implant survival and prosthesis stability. It is demonstrated that 3i implants are predictable and can provide lasting osseointegration leading to improvement of oral function if the recommended surgical and restorative protocol is followed.     

VASOCONSTRICTOR RESPONSES TO COMPONENTS OF THE RENIN-ANGIOTENSIN SYSTEM IN CYCLOSPORIN-INDUCED HYPERTENSION IN THE RAT

1. Since plasma renin activity is increased in cyclosporin A (CsA)-induced hypertension in the rat, the role of the vascular renin-angiotensin system (RAS) in CsA-induced hypertension was investigated in rat mesenteric resistance vessels. 2. Female Wistar rats received CsA (10 mg/kg per day, s.c.) or vehicle for 30 days. CsA treatment increased tail-cuff systolic blood pressure (CsA treated 135 ± 3 mmHg vs control 125 ± 1 mmHg, P<0.0001). 3. Mesenteric resistance arteries (200–300 μm) were isolated and mounted in a microvessel myograph. Concentration-response curves to tetradecapeptide renin substrate (10-¹¹-10^?6 mol/L), angiotensin I (10-^l1-10^?6 mol/L) and angiotensin II (10-¹²-10^?6 mol/L) showed no differences between CsA-treated and control groups. 4. Mesenteric vascular angiotensin-converting enzyme (ACE) characteristics were determined by radioligand binding. There were no differences in the content or affinity of ACE between CsA-treated and control rats. 5. These results suggest that the mesenteric vascular RAS does not play a major role in CsA-induced hypertension in the rat.     

INTERACTION BETWEEN EPIDERMAL GROWTH FACTOR AND ARGININE VASOPRESSIN IN RENAL MEDULLARY MEMBRANES

1. Epidermal growth factor is a potent mitogen that causes natriuresis, diuresis and inhibition of arginine vasopressin-induced water reabsorption. 2. The aim of this study was to determine any interaction between epidermal growth factor and the V1 (vascular) and/or V2 (antidiuretic) arginine vasopressin receptor subtypes. 3. Radioligand binding displacement assays demonstrated that although arginine vasopressin related peptides displaced both radioligands from renal medullary membranes at low concentrations epidermal growth factor displaced neither. 4. Arginine vasopressin V2 receptor second messenger cyclic adenosine monophosphate (CAMP) production was inhibited by epidermal growth factor (IC₅₀ 2 ± 10^?7 mol/L) as was sodium fluoride cAMP production but only at much higher concentrations. 5. Therefore the diuretic effect of epidermal growth factor is not via direct antagonism of arginine vasopressin receptors but seems mediated via inhibition of the V2 second messenger system.     

Effects of mifepristone on rabbit intraocular pressure in the presence and absence of dexamethasone

Topical dexamethasone was used to elevate rabbit intraocular pressure in order to study the interaction with a steroid antagonist, mifepristone. Dexamethasone did not cause a consistently significant increase in intraocular pressure. Animals treated with mifepristone followed by dexamethasone showed no apparent increase in intraocular pressure after dexamethasone, indeed mifepristone caused a lower intraocular pressure than seen in other groups whether in the presence or absence of dexamethasone. Reductions of intraocular pressure when mifepristone was given after 14 days of dexamethasone administration were not found. No conclusion can be reached regarding any dexamethasone antagonism by mifepristone, except that intraocular pressure tended to be lower even in the presence of dexamethasone.     

The value of CT in determining potential instability of simple wedge-compression fractures of the lumbar spine.

PURPOSETo determine whether plain films alone are sufficient in the evaluation of stability of simple wedge-compression fractures of the lumbar spine.METHODSPlain films and CT scans of 53 consecutive patients seen during a 2-year period with lumbar spine fractures were retrospectively reviewed. Six readers blinded to the CT diagnosis independently read each patient''s plain films. Plain-film findings were scored on a five-point graded response scale using criteria proposed by Gehweiler and Daffner. In addition, a fracture was considered to be possibly unstable if there was involvement of more than one vertebral level or greater than 50% loss of anterior vertebral body height. CT findings represented the standard for comparison. CT scans were independently evaluated by three additional readers. Two-column involvement, middle-column involvement alone but with retropulsion, multiple-level involvement, or greater than 50% loss of vertebral height indicated potential instability.RESULTSFor 14 stable and 39 potentially unstable lumbar spine fractures, the pooled (mean) plain-film negative predictive value for detection of potentially unstable fractures was 0.62 (95% confidence interval, 0.53 to 0.70), with a sensitivity of 0.83 (95%, confidence interval; 0.78 to 0.87), and specificity of 0.80 (95% confidence interval, 0.70 to 0.87).CONCLUSIONPlain films are not adequate for determining stability of lumbar spine fractures.     

Factors involved in the anti-cancer activity of the investigational agents LM985 (flavone acetic acid ester) and LM975 (flavone acetic acid)

LM985 has been shown previously to hydrolyse to flavone acetic acid (LM975) in mouse plasma and to produce significant anti-tumour effects in transplantable mouse colon tumours (MAC). It has undergone Phase I clinical trials and dose limiting toxicity was acute reversible hypotension. Substantially higher doses of LM975 can be given clinically without dose limiting toxicity. We have investigated the activity of LM975 against a panel of MAC tumours and also the in vitro cytotoxicity of both LM985 and LM975 in two cell lines derived from MAC tumours. LM985 is considerably more cytotoxic than LM975 in vitro but increased length of exposure to LM975 results in improved activity. Single in vivo injection of LM975 showed no activity against the ascitic tumour MAC 15A, moderate activity against the s.c. poorly differentiated tumour MAC 13 and produced a significant growth delay in the well differentiated MAC 26. These latter responses were considerably enhanced by repeated injection 7 days later. Pharmacokinetic studies in mice following i.p. injection of LM985 demonstrated rapid degradation of LM985 to LM975 in the peritoneum. Length of exposure as well as drug concentration appear important factors in determining anti-tumour responses.     

Alpha 2U-globulin: measurement in rat kidney and relationship to hyaline droplets

The concentration of renal alpha 2U-globulin increased in a dose-dependent manner in adult male but not female rats which received a single dose of 2,2,4-trimethylpentane (TMP). After administration of a single dose of 12 mmol TMP/kg to adult male rats, the renal concentration of alpha 2U-globulin reached a peak at 48 hours and returned to near background level after 7 days. These changes in renal alpha 2U-globulin concentration were closely paralleled by changes in renal hyaline droplet formation. Renal alpha 2U-globulin and hyaline droplets were absent in normal pre-puberty male rats, and neither could be stimulated by a single dose of TMP. alpha 2U-Globulin was localised in the renal cortex of adult male rats, in particular the S2 segment of the proximal tubule. A greater staining intensity due to alpha 2U-globulin was seen in the S2 and adjacent segments after a single dose of TMP. A strong association is suggested between the presence of renal hyaline droplets and the occurrence of alpha 2U-globulin.