Publications

We have reported that pyrroloquinoline quinone (PQQ) improves reproduction, neonatal development, and mitochondrial function in animals by mechanisms that involve mitochondrial related cell signaling pathways. To extend these observations, the influence of PQQ on energy and lipid relationships and apparent protection against ischemia reperfusion injury are described herein. Sprague-Dawley rats were fed a nutritionally complete diet with PQQ added at either 0 (PQQ-) or 2 mg PQQ/Kg diet (PQQ+). Measurements included: 1) serum glucose and insulin, 2) total energy expenditure per metabolic body size (Wt(3/4)), 3) respiratory quotients (in the fed and fasted states), 4) changes in plasma lipids, 5) the relative mitochondrial amount in liver and heart, and 6) indices related to cardiac ischemia. For the latter, rats (PQQ- or PQQ+) were subjected to left anterior descending occlusions followed by 2 h of reperfusion to determine PQQ's influence on infarct size and myocardial tissue levels of malondialdehyde, an indicator of lipid peroxidation. Although no striking differences in serum glucose, insulin, and free fatty acid levels were observed, energy expenditure was lower in PQQ- vs. PQQ+ rats and energy expenditure (fed state) was correlated with the hepatic mitochondrial content. Elevations in plasma di- and triacylglyceride and β-hydroxybutryic acid concentrations were also observed in PQQ- rats vs. PQQ+ rats. Moreover, PQQ administration (i.p. at 4.5 mg/kg BW for 3 days) resulted in a greater than 2-fold decrease in plasma triglycerides during a 6-hour fast than saline administration in a rat model of type 2 diabetes. Cardiac injury resulting from ischemia/reperfusion was more pronounced in PQQ- rats than in PQQ+ rats. Collectively, these data demonstrate that PQQ deficiency impacts a number of parameters related to normal mitochondrial function.

In vitro spine flexibility testing has been performed using a variety of laboratory-specific loading apparatuses and conditions, making test results across laboratories difficult to compare. The application of pure moments has been well established for spine flexibility testing, but to our knowledge there have been no attempts to quantify differences in range of motion (ROM) resulting from laboratory-specific loading apparatuses. Seven fresh-frozen lumbar cadaveric motion segments were tested intact at four independent laboratories. Unconstrained pure moments of 7.5 Nm were applied in each anatomic plane without an axial preload. At laboratories A and B, pure moments were applied using hydraulically actuated spinal loading fixtures with either a passive (A) or controlled (B) XY table. At laboratories C and D, pure moments were applied using a sliding (C) or fixed ring (D) cable-pulley system with a servohydraulic test frame. Three sinusoidal load-unload cycles were applied at laboratories A and B while a single quasistatic cycle was applied in 1.5 Nm increments at laboratories C and D. Non-contact motion measurement systems were used to quantify ROM. In all test directions, the ROM variability among donors was greater than single-donor ROM variability among laboratories. The maximum difference in average ROM between any two laboratories was 1.5° in flexion-extension, 1.3° in lateral bending and 1.1° in axial torsion. This was the first study to quantify ROM in a single group of spinal motion segments at four independent laboratories with varying pure moment systems. These data support our hypothesis that given a well-described test method, independent laboratories can produce similar biomechanical outcomes.

BACKGROUND

Unintentional loss of weight and muscle due to aging and disease has been associated with increased mortality. Wasting and weight loss occur in HIV infection even in the modern era of effective antiretroviral therapy.

METHODS

We determined the association of MRI-measured regional and total skeletal muscle and adipose tissue with 5-year, all-cause mortality in 922 HIV-infected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM).

RESULTS

After 5 years of follow-up, HIV-infected participants with arm skeletal muscle in the lowest tertile had a mortality rate of 23%, compared with 11 and 8% for those in the middle and highest tertiles. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, inflammatory markers, and renal disease, we found that lower arm skeletal muscle, lower leg skeletal muscle and higher visceral adipose tissue (VAT) were each independently associated with increased mortality. Those in the lowest tertile of arm or leg skeletal muscle had higher odds of death [arm: odds ratio (OR) = 2.0, 95% confidence interval (CI) 0.96-4.0; leg: OR = 2.4, 95% CI 1.2-4.8] compared with the highest respective tertiles. Those in the highest tertile of VAT had 2.1-fold higher odds of death (95% CI 1.1-4.0) compared with the lowest VAT tertile.

CONCLUSION

Lower muscle mass and central adiposity appear to be important risk factors for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on body mass index in clinical practice.