Anterior cruciate ligament abnormalities are associated with accelerated progression of knee joint degeneration in knees with and without structural knee joint abnormalities: 96-month data from the Osteoarthritis Initiative.

OBJECTIVE: To compare progression over 8 years in knee compositional cartilage degeneration and structural joint abnormalities in knees with different types of anterior cruciate ligament (ACL) abnormalities over 8 years. METHOD: Baseline MR images of the right knees of 1899 individuals of the Osteoarthritis Initiative (OAI) with no evidence of or mild to moderate radiographic osteoarthritis were assessed for nontraumatic ACL abnormalities. The knees of 91 individuals showed nontraumatic ACL abnormalities (age 60.6 ± 9.8 y, 46 females; mucoid degeneration (MD), N = 37; complete tear (CT), N = 22; partial tear (PT), N = 32) and were frequency-matched to 91 individuals with normal ACL. MRIs were assessed for knee joint abnormalities using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) and cartilage T2 mapping at baseline, 4- and 8-year follow-up. RESULTS: Over 8 years, cartilage T2 values of the medial tibia showed a significantly greater increase in individuals with MD, PT or CT compared to those with normal ACL (adjusted rate of change/year [95% confidence interval], normal ACL: 0.06 [0.01, 0.23], MD: 0.34 [0.07, 0.73], PT, 0.21 [0.02, 0.33], CT, 0.51 [0.16, 0.78]), indicating an association of ACL abnormalities and an increased progression rate of cartilage degeneration in subjects with and without knee joint degeneration. This effect was also seen in cartilage T2 values averaged over all compartments (normal ACL: 0.08 [0.05, 0.20] vs abnormal ACL: 0.27 [0.06, 0.56]). CONCLUSIONS: Over 8 years, higher progression rates of cartilage degeneration, especially in the medial tibia, were associated with ACL abnormalities compared to those with normal ACL, in subjects with and without knee joint abnormalities.

Weight loss regimen in obese and overweight individuals is associated with reduced cartilage degeneration: 96-month data from the Osteoarthritis Initiative.

PURPOSE: To investigate change in knee cartilage composition over 96 months in overweight and obese participants with constant weight compared to those with weight loss (WL), and to assess how different WL regimens are associated with these changes. METHODS: We studied right knees of 760 participants (age 62.6 ± 9.0y; 465 females) with a baseline body mass index (BMI) >25 kg/m2 from the Osteoarthritis Initiative with mild to moderate or with risk factors for knee osteoarthritis. Participants losing weight (>5% of baseline BMI over 72 months; N = 380) were compared to controls with stable weight (SW, N = 380). Participants losing weight were categorized based on WL method (diet and exercise, diet only, exercise only) and compared to those with stable weight. Magnetic resonance imaging (MRI) at 3T was performed at baseline, 48- and 96-months. The association of WL and WL method with change in cartilage composition, measured with T2 mapping, was analyzed using mixed random effects models. RESULTS: Compared to SW, WL was associated with a significantly slower increase in global (averaged over all compartments) cartilage T2 (adjusted mean difference of change in T2 ms/year [95% CI] between the groups: 0.24 [0.20, 0.41] ms/year; P < 0.001) and global deep layer cartilage T2 0.35 [0.20, 0.42] ms/year; P < 0.001), suggesting slower cartilage deterioration. Compared to the SW group, slower increases in global T2 were observed in the diet and diet and exercise groups, but not in the exercise only group (P = 0.042, P = 0.003 and P = 0.85, respectively). CONCLUSION: Our results suggest that WL may slow knee cartilage degeneration over 96 months, and that these potential benefits may differ by method of WL.

Inhibition of tryptophan hydroxylase abolishes fatigue induced by central tryptophan in exercising rats.

Fatigue during prolonged exercise is related to brain monoamines concentrations, but the mechanisms underlying this relationship have not been fully elucidated. We investigated the effects of increased central tryptophan (TRP) availability on physical performance and thermoregulation in running rats that were pretreated with parachlorophenylalanine (p-CPA), an inhibitor of the conversion of TRP to serotonin. On the 3 days before the experiment, adult male Wistar rats were treated with intraperitoneal (ip) injections of saline or p-CPA. On the day of the experiment, animals received intracerebroventricular (icv) injections of either saline or TRP (20.3 µM) and underwent a submaximal exercise test until fatigue. Icv TRP-treated rats that received ip saline presented higher heat storage rate and a 69% reduction in time to fatigue compared with the control animals. Pretreatment with ip p-CPA blocked the effects of TRP on thermoregulation and performance. Moreover, ip p-CPA administration accelerated cutaneous heat dissipation when compared with saline-pretreated rats. We conclude that an elevated availability of central TRP interferes with fatigue mechanisms of exercising rats. This response is modulated by serotonergic pathways, because TRP effects were blocked in the presence of p-CPA. Our data also support that a depletion of brain serotonin facilitates heat loss mechanisms during exercise.

Fatigue is mediated by cholinoceptors within the ventromedial hypothalamus independent of changes in core temperature.

We investigated brain mechanisms modulating fatigue during prolonged physical exercise in cold environments. In a first set of studies, each rat was subjected to three running trials in different ambient temperatures (T(a)). At 8 °C and 15 °C, core body temperature (T(core)) decreased and increased, respectively, whereas at 12 °C, the T(core) did not change throughout the exercise. In another set of experiments, rats were randomly assigned to receive bilateral 0.2 µL injections of 2.5 × 10(-2) M methylatropine or 0.15 M NaCl solution into the ventromedial hypothalamic nuclei (VMH). Immediately after the injections, treadmill exercise was started. Each animal was subjected to two experimental trials at one of the following T(a) : 5 °C, 12 °C or 15 °C. Muscarinic blockade of the VMH reduced the time to fatigue (TF) in cold environments by 35-37%. In all T(a) studied, methylatropine-treated rats did not present alterations in T(core) and tail skin temperature compared with controls. These results indicate that, below the zone of thermoneutrality, muscarinic blockade of the VMH decreases the TF, independent of changes in T(core). In conclusion, our data suggest that VMH muscarinic transmission modulates physical performance, even when the effects of thermoregulatory adjustments on fatigue are minimal.

Physical exercise-induced cardiovascular adjustments are modulated by muscarinic cholinoceptors within the ventromedial hypothalamic nucleus.

The effects of blocking ventromedial hypothalamic nucleus (VMH) muscarinic cholinoceptors on cardiovascular responses were investigated in running rats. Animals were anesthetized with pentobarbital sodium and fitted with bilateral cannulae into the VMH. After recovering from surgery, the rats were familiarized to running on a treadmill. The animals then had a polyethylene catheter implanted into the left carotid artery to measure blood pressure. Tail skin temperature (T(tail)), heart rate, and systolic, diastolic and mean arterial pressure were measured after bilateral injections of 0.2 microl of 5 x 10(-9) mol methylatropine or 0.15 M NaCl solution into the hypothalamus. Cholinergic blockade of the VMH reduced time to fatigue by 31 % and modified the temporal profile of cardiovascular and T(tail) adjustments without altering their maximal responses. Mean arterial pressure peak was achieved earlier in methylatropine-treated rats, which also showed a 2-min delay in induction of tail skin vasodilation, suggesting a higher sympathetic tonus to peripheral vessels. In conclusion, muscarinic cholinoceptors within the VMH are involved in a neuronal pathway that controls exercise-induced cardiovascular adjustments. Furthermore, blocking of cholinergic transmission increases sympathetic outflow during the initial minutes of exercise, and this higher sympathetic activity may be responsible for the decreased performance.

Intrinsic exercise capacity is related to differential monoaminergic activity in the rat forebrain.

Monoamines levels in central nervous system have been associated with exercise performance and fatigue. The present study investigated whether intrinsic exercise capacity is associated with differential activity of monoamines in the caudate-putamen (CPu) and accumbens (ACC) nucleus. Male Wistar rats were subjected to a progressive testing protocol. Based on the maximal time of exercise in the progressive testing protocol (TEPmax), the animals were divided into low-performance (LP), high-performance (HP), and standard-performance (SP) groups. After classification, eight animals in each group were chosen randomly and evaluated in two experimental situations: rest (n=8) or moderate exercise (ME) at 60% of maximal velocity (n=8). The CPu and ACC were dissected for analyses of monoamine levels. At rest, HP rats exhibited higher 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine (DA) ratio and lower serotonin (5-HT) concentration compared other groups, and lower 5-hydroxyindoleacetic (5-HIAA) compared with the LP rats. The ME resulted in increased DOPAC/DA ratio in the CPu of all experimental groups. In both the CPu and ACC, ME increased 5-HIAA levels in SP and HP rats and 5-HIAA/5-HT ratio only in HP rats. Thus, our findings demonstrate that rats with natural intrinsic differences in performance to exercise exhibit alterations in dopaminergic and serotonergic systems at rest and after ME exercise until fatigue.

Lipoprotein (a) in subjects with or without coronary artery disease: relation to clinical history and risk factors.

Lipoprotein (a) [Lp(a)] is an atherogenic lipoprotein resembling low-density lipoprotein (LDL) but with an additional apoprotein (apo), apo(a). To determine whether plasma Lp(a) levels can influence the clinical presentation and extent of coronary artery disease (CAD), Lp(a), plasma lipids and apolipoproteins were determined in 203 Caucasian subjects with CAD and in 66 subjects without CAD, all confirmed by cinecoronariography. CAD patients were divided into groups according to their clinical history. The extent of the disease was evaluated by a scoring system. Lp(a) was elevated in CAD patients compared to subjects without CAD. However, there was no difference between patients that had myocardial infarction as the first manifestation of the disease and those who had only angina pectoris for at least two years. Plasma Lp(a) levels were correlated with extent of the disease. Among patients with CAD, Lp(a) was higher in females. Lp(a) was also studied separately in 29 Black subjects, 12 without CAD and 17 with CAD. In Black subjects, Lp(a) was higher than in Caucasians but there was no difference between subjects with and without CAD. Among the other risk factors studied, only plasma apo B levels and smoking were correlated with CAD.

[Lipoprotein (a) plasma levels in normal subjects and patients with coronary disease confirmed by coronary cineangiography]. / Níveis plasmáticos de lipoproteína (a) em indivíduos normais e portadores de doença coronariana confirmada por cinecoronariografia.

PURPOSE: To evaluate the plasma concentration of lipoprotein (a) (Lp(a) in subjects with normal or altered coronary angiography, as a risk factor of atherosclerosis in a Brazilian population. PATIENTS AND METHOD: Lp(a) plasma levels were determined by radioimmunoassay in 31 subjects with normal angiography and in 131 subjects with atherosclerosis. Plasma cholesterol, triglycerides, apolipoprotein A, A1 and B were also determined as well as risk factors like systemic arterial hypertension, smoking habit, diabetes and physical activity. RESULTS: Subjects with coronary disease had Lp(a) plasma levels of 41.9 mg/dl, compared to 23.9 mg/dl found in the normal group. Coronary artery disease risk was increased 2.3 times in those with plasma Lp(a) levels equal or above 25 mg/dl, compared to those with levels below this boundary. As to other known risk factors, only smoking habit has shown correlation with coronary artery disease. CONCLUSION: We confirmed the value of Lp(a) as a risk factor of coronary heart disease.

Lipoprotein (a) in subjects with or without coronary artery disease: relation to clinical history and risk factors

Lipoprotein (a) [Lp(a)] is an atherogenic lipoprotein resembling low-density lipoprotein (LDL) but with an additional apoprotein (apo), apo(a). To determine whether plasma Lp(a) levels can influence the clinical presentation and extent of coronary artery disease (CAD), Lp(a), plasma lipids and apolipoproteins were determined in 203 Caucasian subjects with CAD and in 66 subjects without CAD, all confirmed by cinecoronariography. CAD patients were divided into groups according to their clinical history. The extent of the disease was evaluated by a scoring system. Lp(a) was elevated in CAD patients compared to subjects without CAD. However, there was no difference between patients that had myocardial infarction as the first manifestation of the disease and those who had only angina pectoris for at least two years. Plasma lp(a) levels were correlated with extent of the disease. Among patients with CAD, Lp(a) was higher in females. Lp(a) was also studied separately in 29 Black subjects, Lp(a) was higher than in Caucasians but there was no difference between subjects with and without CAD. Among the other risk factors studied, only plasma apo B levels and smoking were correlated with CAD