Tear buffering in contact lens wearers

The buffering capacity of tears collected from contact lens wearers was compared to that from non-contact lens wearers. Three groups of subjects were investigated: 6 subjects not wearing contact lenses, 3 subjects wearing rigid contact lenses, and 3 subjects wearing hydrogel contact lenses. Each of the 12 subjects provided, on 6 separate occasions, 100 microliters of tears. The pH of the tears was measured with a closed chamber, temperature stabilized micro-electrode system firstly on collection and then after titration with acid and base. In all, 28 titration steps across the acid-base spectrum were completed for each subject's tears on each occasion. These tear pH responses to acid-base challenge were compared to that of unbuffered distilled water for the same titration procedure. There was no statistically significant effect of contact lens wear on tear buffering capacity, but considerable inter-subject variability was noted.     

Controlled Release of Substituted Benzole and Naphthoic Acids Using Carbopol ® Gels: Measurement of Drug Concentration Profiles and Correlation to Release Rate Kinetics

Purpose. The objective of this study is to correlate drug release mechanism with measured drug concentration profiles in gel layers of Carbopol^® matrices containing mesalamine or benzoic acid. Methods. Release rate experiments with Carbopol^® matrices were performed using a rotating disk apparatus. Matrices were frozen and the gel layer in the matrices was sliced using a microtome in a cryostat. Drug concentration profiles were determined by direct measurement of the concentration of the drug in the gel slices. The pH of the slices was measured using microelectrodes, and water content was measured by Karl Fisher titration. Results. The concentration gradient in mesalamine matrices decreased over time and correlated with square root of time release rate kinetics. The concentration profiles of benzoic acid were unchanged over time and correlated with zero order release rate kinetics. Carbopol gel layers were highly hydrated (93–95% water). Gel layers in matrices with mesalamine had a more alkaline microenvironmental pH. This higher pH resulted in increased growth of the thickness of the gel layer and a reduction drug diffusivity in comparison to benzoic acid matrices. Conclusions. The release rate kinetics of mesalamine and benzoic acid correlated to the measured concentration profiles. The shape of the concentration profiles is determined by the rate of growth of the Carbopol^® gel layer and drug diffusivity.     

An analysis of an older driver evaluation program

OBJECTIVES: To identify elements of an older driver evaluation program that predict driving performance in older adults. SETTING: Outpatient medical clinic in an academic medical center. DESIGN: A retrospective analysis. PARTICIPANTS: Six hundred sixty-four older adults who were referred to an older driver evaluation program. MEASUREMENTS: A physician trained in geriatric medicine and a clinical geriatric nurse specialist oversaw an experienced driving evaluator and an occupational therapist who conducted assessments of older persons' functional status; reaction time; driving skills; and cognitive, hearing, and vision abilities. Self-report data along with a medical history submitted by patients' primary care physicians supplemented the clinical assessments. RESULTS: A multinomial logistic regression revealed that the Mini-Mental State Examination (MMSE), cues needed with the Trail Making Test, Part B, grip strength, and an interaction effect between the MMSE and reaction time constituted the most parsimonious model for predicting on-the-road performance. A receiver operating characteristic analysis indicated that this index had good sensitivity but low specificity. A binomial regression comparing imperfect and perfect drivers demonstrated the significance of the Traffic Sign and Visual Perception tests. CONCLUSION: Clinicians should employ a multilevel screening process that includes initial cognitive tests, such as the MMSE and the Trail Making Test, Part B, although more studies of driving evaluation programs in medical settings that include random samples of older drivers are needed.     

Ribo-polymerase chain reaction--a facile method for the preparation of chimeric RNA/DNA applied to DNA sequencing

We describe ribo-polymerase chain reaction (PCR), a method for the preparation of chimeric RNA/DNA. The RNA/DNA chimeric nucleic acids are generated directly from genomic DNA starting templates with two locus-specific primers, three nucleotides in their deoxy form and the fourth in its ribo form, a DNA polymerase capable of incorporating ribo bases, a suitable buffer, and thermal cycling. We have applied ribo-PCR to resequence DNA by directly fragmenting the RNA/DNA chimeras with alkali and analyzing the fragments by mass spectrometry (MS). Mass fingerprint is used to identify deviations from the reference sequence. This method readily detects homozygous sequence deviations as well as heterozygous positions directly from genomic DNA samples. With the high-throughput capability of MS, this facile method is well suited for screening DNA sequences of limited regions of the genome in a large number of individuals. It can also be used to sequence multiple distant genomic loci in a single reaction. This novel ribo-PCR resequencing protocol was applied to different genomic loci involving nitric oxide synthase 1 (NOS1) and H19 in 30 individuals and SLCO1B1 in 95 individuals.     

Partial heat acclimation of athletes with spinal cord lesion

Heat acclimation (HA) can improve thermoregulatory stability in able-bodied athletes in part by an enhanced sweat response. Athletes with spinal cord lesion are unable to sweat below the lesion and it is unknown if they can HA. Five paralympic shooting athletes with spinal cord lesion completed seven consecutive days HA in hot conditions (33.4 ± 0.6 °C, 64.8 ± 3.7 %rh). Each HA session consisted of 20 min arm crank exercise at 50 % $ \dot{V}{\text{O}}_{{ 2 {\text{peak}}}} $ followed by 40 min rest, or simulated shooting. Aural temperature (T _aur) was recorded throughout. Body mass was assessed before and after each session and a sweat collection swab was fixed to T12 of the spine. Fingertip whole blood was sampled at rest on days 1 and 7 for estimation of the change in plasma volume. Resting T _aur declined from 36.3 ± 0.2 °C on day 1 to 36.0 ± 0.2 °C by day 6 (P < 0.05). During the HA sessions mean, T _aur declined from 37.2 ± 0.2 °C on day 1, to 36.7 ± 0.3 °C on day 7 (P < 0.05). Plasma volume increased from day 1 by 1.5 ± 0.6 % on day 7 (P < 0.05). No sweat secretion was detected or changes in body mass observed from any participant. Repeated hyperthermia combined with limited evaporative heat loss was sufficient to increase plasma volume, probably by alterations in fluid regulatory hormones. In conclusion, we found that although no sweat response was observed, athletes with spinal cord lesion could partially HA.     

The unstable urethra in the female

The clinical and urodynamic characteristics of 54 women with unstable urethras (falls of urethral pressures of at least 20 cm H2O) were compared with those of 171 patients with stable urethras. The unstable-urethra patients were younger and presented with an increased incidence of marked urgency and a lower incidence of genuine stress incontinence. The average urethral pressure fall was preceded by a 6-cm increase in maximum urethral pressure. The mean (+/- SD) fall of urethral pressure was 30 +/- 12 cm H2O and the average duration of the event was 8 seconds. The level of the urethral pressure fall was not influenced by bladder volume but correlated positively with higher maximum urethral pressures. The present findings suggest that the unstable urethra plays a limited role in genuine stress incontinence but may be linked with the unstable detrusor.     

Ligand-binding affinity of the type 1 and 2 inositol 1,4,5-trisphosphate receptors: effect of the membrane environment

The inositol 1,4,5-trisphosphate (InsP3) receptor is essential for Ca2+ release from intracellular stores. There are three InsP3 receptor types which are targets for several types of regulation. Ca2+, phosphorylation, and protein-protein interactions may contribute to the complex pattern of the Ca2+ signal in stimulated cells. Furthermore, the 3 receptor types could have different affinities for InsP3. We compared the affinities of the type 1 receptor from the cerebellum with the liver type 2 receptor both in their membrane environment and after isolation by immunoprecipitation. Measurements of [3H]InsP3 binding in a cytosol-like medium revealed that the Kd of the liver receptor (45 +/- 5 nM, N = 14) was higher than the Kd of the cerebellar receptor (28 +/- 3 nM, N = 9). Solubilization and immunopurification of the liver InsP3 receptor resulted in a 10-fold increase in its affinity for InsP3. The affinity of the cerebellar receptor did not change under these conditions. Therefore, the extraction of the liver and the cerebellar receptors from their membrane environments induced an inversion of their relative affinities. Treatment of liver membranes with low concentrations of detergents also increased the affinity for InsP3 binding. These data indicate that the type 1 and the type 2 InsP3 receptors have different affinities for InsP3 and that the properties of the type 2 receptor are strongly regulated by hydrophobic interactions within its membrane environment.     

Synthesis and antitumour evaluation of 4-bromophenyl semicarbazones

4-Bromophenyl semicarbazone derivatives have been synthesized and their chemical structures have been confirmed by means of their IR, 1H-NMR data and by elemental analyses. The in vitro evaluation in the 3-cell line, one dose primary anticancer assay is described. The 4-bromo substituted p-nitrobenzylidene phenyl semicarbazone (5) showed significant activity against breast MCF7 cell line and was further evaluated for potential anticancer activity in an in vitro human disease-oriented tumour cell line screening panel that consisted of 59 human tumour cell lines arranged in nine subpanels, representing diverse histologies. Melanoma UACC-62 cell line was relatively more sensitive to compounds 5 (growth inhibitions: GI50 = 15.3 mumol/l).