A cetylated fatty acid topical cream with menthol reduces pain and improves functional performance in individuals with arthritis

This investigation was an extension of a previous study conducted in our laboratory in which we showed that 1 month of treatment with a topical cream (Celadrin) consisting of cetylated fatty acids was effective for reducing pain and improving functional performance in individuals with osteoarthritis (OA) of the knee (Kraemer et al., Journal of Rheumatology, 2004). We wanted to verify that the addition of menthol to the compound would produce a similar percentage of improvement in therapeutic effects. We used a single treatment group with a pre-post experimental design to examine % treatment changes. Individuals diagnosed with OA of the knee (N = 10; age, 66.4 +/- 11.5 years) and severe pain (e.g., OA, rheumatoid arthritis) of the elbow (N = 8; age, 59.1 +/- 18.2 years) and wrist (N = 10; age, 60.3 +/- 16.8 years) were tested for pain and functional performance before and after 1 week of treatment with a topical cream consisting of cetylated fatty acids and menthol applied twice per day. In individuals with knee OA, significant improvements in stair-climbing ability (about 12%), "up-and-go" performance (about 12%), balance and strength (about 16.5%), and range of motion (about 3.5%) were observed, as were reductions in pain. In individuals with severe pain of the elbow and wrist, significant improvements in dynamic (about 22 and 24.5%, respectively) and isometric (about 33 and 42%, respectively) local muscular endurance were observed, as was a reduction in pain. Neither group demonstrated significant changes in maximal grip strength or maximal force production. One week of treatment with a topical cream consisting of cetylated fatty acids and menthol was similarly effective for reducing pain and improving functional performance in individuals with arthritis of the knee, elbow, and wrist. The % changes were consistent with our prior work on the compound without menthol. Further work is needed to determine the impact of menthol in such a cream. Nevertheless, our data support the use of a topical cream consisting of cetylated fatty acids (with or without menthol) for enhancing the potential for exercise training in this population.     

Plasma vasopressin and aldosterone responses to oral and intravenous saline rehydration.

This investigation examined plasma arginine vasopressin (AVP) and aldosterone (Ald) responses to 1) oral and intravenous (IV) methods of rehydration (Rh) and 2) different IV Rh osmotic loads. We hypothesized that AVP and Ald responses would be similar between IV and oral Rh and that the greater osmolality and sodium concentration of a 0.9% IV saline treatment would stimulate a greater AVP response compared with a 0.45% IV saline treatment. On four occasions, eight men (age: 22.1 +/- 0.8 yr; height: 179.6 +/- 1.5 cm; weight: 73.6 +/- 2.5 kg; maximum O(2) consumption: 57.9 +/- 1.6 ml. kg(-1). min(-1), body fat: 7.7 +/- 0.9%) performed a dehydration (Dh) protocol (33 degrees C) to establish a 4-5% reduction in body weight. After Dh, subjects underwent each of three randomly assigned Rh (back to -2% body wt) treatments (0.9 and 0.45% IV saline, 0.45% oral saline) and a no Rh treatment during the first 45 min of a 100-min rest period. Blood samples were obtained pre-Dh, immediately post-Dh, and at 15, 35, and 55 min post-Rh. Before Dh, plasma AVP and Ald were not different among treatments but were significantly elevated post-Dh. In general, at 15, 35, and 55 min post-Rh, AVP, Ald, osmolality, and plasma volume shifts did not differ between IV and oral fluid replacement. These results demonstrated that the manner in which plasma AVP and Ald responded to oral and IV Rh or to different sodium concentrations (0.9 vs. 0.45%) was not different given the degree of Dh (-4.5% body wt) and Rh and amount of time after Rh (55 min).     

Ribonucleotide Reductase Subunit M2 Predicts Survival in Subgroups of Patients with Non-Small Cell Lung Carcinoma: Effects of Gender and Smoking Status

BackgroundRibonucleotide reductase catalyzes the conversion of ribonucleotide diphosphates to deoxyribonucleotide diphosphates. The functional enzyme consists of two subunits - one large (RRM1) and one small (RRM2 or RRM2b) subunit. Expression levels of each subunit have been implicated in prognostic outcomes in several different types of cancers.ResultsIn non-small cell lung cancer (NSCLC), RRM2 expression was strongly predictive of disease-specific survival in women, non-smokers and former smokers who had quit at least 10 years prior to being diagnosed with lung cancer. Higher expression was associated with worse survival. This was not the case for men, current smokers and those who had stopped smoking for shorter periods of time. RRM1 was not predictive of survival outcomes in any subset of the patient group.ConclusionRRM2, but not RRM1, is a useful predictor of survival outcome in certain subsets of NSCLC patients.     

Examining the influence of hydration status on physiological responses and running speed during trail running in the heat with controlled exercise intensity

The purpose of this study was to determine the effects of dehydration at a controlled relative intensity on physiological responses and trail running speed. Using a randomized, controlled crossover design in a field setting, 14 male and female competitive, endurance runners aged 30 ± 10.4 years completed 2 (hydrated [HY] and dehydrated [DHY]) submaximal trail runs in a warm environment. For each trial, the subjects ran 3 laps (4 km per lap) on trails with 4-minute rests between laps. The DHY were fluid restricted 22 hours before the trial and during the run. The HY arrived euhydrated and were given water during rest breaks. The subjects ran at a moderate pace matched between trials by providing pacing feedback via heart rate (HR) throughout the second trial. Gastrointestinal temperature (T(GI)), HR, running time, and ratings of perceived exertion (RPE) were monitored. Percent body mass (BM) losses were significantly greater for DHY pretrial (-1.65 ± 1.34%) than for HY (-0.03 ± 1.28%; p < 0.001). Posttrial, DHY BM losses (-3.64 ± 1.33%) were higher than those for HY (-1.38 ± 1.43%; p < 0.001). A significant main effect of T(GI) (p = 0.009) was found with DHY having higher T(GI) postrun (DHY: 39.09 ± 0.45°C, HY: 38.71 ± 0.45°C; p = 0.030), 10 minutes post (DHY: 38.85 ± 0.48°C, HY: 38.46 ± 0.46°C; p = 0.009) and 30 minutes post (DHY: 38.18 ± 0.41°C, HY: 37.60 ± 0.25°C; p = 0.000). The DHY had slower run times after lap 2 (p = 0.019) and lap 3 (p = 0.025). The DHY subjects completed the 12-km run 99 seconds slower than the HY (p = 0.027) subjects did. The RPE in DHY was slightly higher than that in HY immediately postrun (p = 0.055). Controlling relative intensity in hypohydrated runners resulted in slower run times, greater perceived effort, and elevated T(GI), which is clinically meaningful for athletes using HR as a gauge for exercise effort and performance.     

The effects of ten weeks of resistance and combined plyometric/sprint training with the Meridian Elyte athletic shoe on muscular performance in women

The purpose of this investigation was to examine the combined effects of resistance and sprint/plyometric training with or without the Meridian Elyte athletic shoe on muscular performance in women. Fourteen resistance-trained women were randomly assigned to one of 2 training groups: (a) an athletic shoe (N = 6) (AS) group or (b) the Meridian Elyte (N = 8) (MS) group. Training was performed for 10 weeks and consisted of resistance training for 2 days per week and 2 days per week of sprint/plyometric training. Linear periodized resistance training consisted of 5 exercises per workout (4 lower body, 1 upper body) for 3 sets of 3-12 repetition maximum (RM). Sprint/plyometric training consisted of 5-7 exercises per workout (4-5 plyometric exercises, 40-yd and 60-yd sprints) for 3-6 sets with gradually increasing volume (8 weeks) followed by a 2-week taper phase. Assessments for 1RM squat and bench press, vertical jump, broad jump, sprint speed, and body composition were performed before and following the 10-week training period. Significant increases were observed in both AS and MS groups in 1RM squat (12.0 vs. 14.6 kg), bench press (6.8 vs. 7.4 kg), vertical jump height (3.3 vs. 2.3 cm), and broad jump (17.8 vs. 15.2 cm). Similar decreases in peak 20-, 40-, and 60-m sprint times were observed in both groups (20 m: 0.14 vs. 0.11 seconds; 40 m: 0.29 vs. 0.34 seconds; 60 m: 0.45 vs. 0.46 seconds in AS and MS groups, respectively). However, when sprint endurance (the difference between the fastest and slowest sprint trials) was analyzed, there was a significantly greater improvement at 60 m in the MS group. These results indicated that similar improvements in peak sprint speed and jumping ability were observed following 10 weeks of training with either shoe. However, high-intensity sprint endurance at 60 m increased to a greater extent during training with the Meridian Elyte athletic shoe.     

In vivo endothelial gene regulation in diabetes

Background

In comparison to the well established changes in compliance that occur at the large vessel level in diabetes, much less is known about the changes in compliance of the cardiovascular system at the end-organ level. The aim of this study was therefore to examine whether there was a correlation between resistance of the intrarenal arteries of the kidney and compliance of the left ventricle, as estimated by measurements of diastolic function, in subjects with type 2 diabetes.

Methods

We studied 167 unselected clinic patients with type 2 diabetes with a kidney duplex scan to estimate intrarenal vascular resistance, i.e. the resistance index (RI = peak systolic velocity-minimum diastolic velocity/peak systolic velocity) and a transthoracic echocardiogram (TTE) employing tissue doppler studies to document diastolic and systolic ventricular function.

Results

Renal RI was significantly higher in subjects with diastolic dysfunction (0.72 ± 0.05) when compared with those who had a normal TTE examination (0.66 ± 0.06, p < 0.01). Renal RI values were correlated with markers of diastolic dysfunction including the E/Vp ratio (r = 0.41, p < 0.001), left atrial area (r = 0.36, p < 0.001), the E/A ratio (r = 0.36, p < 0.001) and the E/E' ratio (r = 0.31, p < 0.001). These associations were independent of systolic function, hypertension, the presence and severity of chronic kidney disease, the use of renin-angiotensin inhibitors and other potentially confounding variables.

Conclusion

Increasing vascular resistance of the intrarenal arteries was associated with markers of diastolic dysfunction in subjects with type 2 diabetes. These findings are consistent with the hypothesis that vascular and cardiac stiffening in diabetes are manifestations of common pathophysiological mechanisms.     

Principles of glomerular organization in the human olfactory bulb--implications for odor processing

Olfactory sensory neurons (OSN) in mice express only 1 of a possible 1,100 odor receptors (OR) and axons from OSNs expressing the same odor receptor converge into approximately 2 of the 1,800 glomeruli in each olfactory bulb (OB) in mice; this yields a convergence ratio that approximates 2:1, 2 glomeruli/OR. Because humans express only 350 intact ORs, we examined human OBs to determine if the glomerular convergence ratio of 2:1 established in mice was applicable to humans. Unexpectedly, the average number of human OB glomeruli is >5,500 yielding a convergence ratio of approximately 16:1. The data suggest that the initial coding of odor information in the human OB may differ from the models developed for rodents and that recruitment of additional glomeruli for subpopulations of ORs may contribute to more robust odor representation.     

The early adaptive evolution of calmodulin

Interaction between gene duplication and natural selection in molecular evolution was investigated utilizing a phylogenetic tree constructed by the parsimony procedure from amino acid sequences of 50 calmodulin- family protein members. The 50 sequences, belonging to seven protein lineages related by gene duplication (calmodulin itself, troponin-C, alkali and regulatory light chains of myosin, parvalbumin, intestinal calcium-binding protein, and glial S-100 phenylalanine-rich protein), came from a wide range of eukaryotic taxa and yielded a denser tree (more branch points within each lineage) than in earlier studies. Evidence obtained from the reconstructed pattern of base substitutions and deletions in these ancestral loci suggests that, during the early history of the family, selection acted as a transforming force on expressed genes among the duplicates to encode molecular sites with new or modified functions. In later stages of descent, however, selection was a conserving force that preserved the structures of many coadapted functional sites. Each branch of the family was found to have a unique average tempo of evolutionary change, apparently regulated through functional constraints. Proteins whose functions dictate multiple interaction with several other macromolecules evolved more slowly than those which display fewer protein-protein and protein-ion interactions, e.g., calmodulin and next troponin-C evolved at the slowest average rates, whereas parvalbumin evolved at the fastest. The history of all lineages, however, appears to be characterized by rapid rates of evolutionary change in earlier periods, followed by slower rates in more recent periods. A particularly sharp contrast between such fast and slow rates is found in the evolution of calmodulin, whose rate of change in earlier eukaryotes was manyfold faster than the average rate over the past 1 billion years. In fact, the amino acid replacements in the nascent calmodulin lineage occurred at residue positions that in extant metazoans are largely invariable, lending further support to the Darwinian hypothesis that natural selection is both a creative and a conserving force in molecular evolution.