Target engagement and intracellular delivery of mono- and bivalent LDL receptor-binding peptide-cargo conjugates: Implications for the rational design of new targeted drug therapies.

Targeted delivery to specific tissues and subcellular compartments is of paramount importance to optimize therapeutic or diagnostic interventions while minimizing side-effects. Using recently identified LDL receptor (LDLR) -targeting small synthetic peptide-vectors conjugated to model cargos of different nature and size, we investigated in LDLR-expressing cells the impact of vector-cargo molecular engineering and coupling valency, as well as the cellular exposure duration on their target engagement and intracellular trafficking and delivery profiles. All vector-cargo conjugates evaluated were found to be delivered to late compartments together with the natural ligand LDL, although to varying extents and with different kinetics. Partial recycling together with the LDLR was also consistently observed. Under continuous cellular exposure, the extent of intracellular vector-cargo delivery primarily relies on their endosomal unloading potential. In this condition, the highest intracellular delivery potential was observed with a monovalent conjugate displaying a rather high LDLR dissociation rate. On the contrary, under transient cellular exposure followed by chase, low dissociation-rate bivalent conjugates revealed a higher intracellular delivery potential than the monovalent conjugate. This was shown to rely on their ability to undergo multiple endocytosis-recycling rounds, with limited release in the ligand-free medium. The absence of reciprocal competition with the natural ligand LDL on their respective intracellular trafficking was also demonstrated, which is essential in terms of potential safety liabilities. These results demonstrate that not only molecular engineering of new therapeutic conjugates of interest, but also the cellular exposure mode used during in vitro evaluations are critical to anticipate and optimize their delivery potential.

[A microcytic sideroblastic anemia successfully treated with B6 vitamin]. / Une anémie microcytaire sidéroblastique carentielle traitée efficacement par de la vitamine B6.

INTRODUCTION: Sideroblastic anemia is a rare cause of microcytic anemia, which is characterized by ring sideroblasts on bone marrow aspirate. This anemia can be congenital or acquired. CASE REPORT: We report the case of an alcoholic 49-year-old man who presented with a severe microcytic sideroblastic anemia related to pyridoxine (B6 vitamin) deficiency. Acid folic deficiency was associated. The blood count normalized within one month after vitamin supplementation. CONCLUSION: Pyridoxine deficiency must be sought in sideroblastic anemia in patients at risk.

Bortezomib inhibits C2C12 growth by inducing cell cycle arrest and apoptosis.

Proteosome inhibitors such as bortezomib (BTZ) have been used to treat muscle wasting in animal models. However, direct effect of BTZ on skeletal muscle cells has not been reported. In the present study, our data showed that C2C12 cells exhibited a dose-dependent decrease in cell viability in response to increasing concentrations of BTZ. Consistent with the results of cell viability, Annexin V/PI analysis showed a significant increase in apoptosis after exposing the cells to BTZ for 24h. The detection of cleaved caspase-3 further confirmed apoptosis. The apoptosis induced by BTZ was associated with reduced expression of p-ERK. Cell cycle analysis revealed that C2C12 cells underwent G2/M cell cycle arrest when incubated with BTZ for 24h. Furthermore, BTZ inhibited formation of multinucleated myotubes. The inhibition of myotube formation was accompanied by decreased expression of Myogenin. Our data suggest that BTZ induces cell death and inhibits differentiation of C2C12 cells at clinically relevant doses.

Towards the conservation of crucian carp Carassius carassius: understanding the extent and causes of decline within part of its native English range.

The extent and causes of crucian carp Carassius carassius decline were assessed during an initial study of c. 25 ponds in north Norfolk, eastern England, U.K., which was then replicated (a validation study) on another c. 25 ponds in an adjacent area. Of these ponds, c. 40 are known to have contained C. carassius during the 1970s-1980s. In the initial and validation studies, C. carassius were found in only 11 of these ponds, yielding declines of 76% (five of 21 ponds) and 68% (six of 19 ponds), respectively (72% decline overall). Non-native cyprinids, including goldfish Carassius auratus and common carp Cyprinus carpio and their hybrids with C. carassius, were observed in 20% of the ponds. Causes of C. carassius local extinction from 21 ponds were confidently determined as desiccation due to drought, terrestrialization and habitat deterioration, hybridization and competition with non-native cyprinids, agricultural land reclamation and predation (after the introduction of pike Esox lucius). This study led to C. carassius being designated as a Biodiversity Action Plan (BAP) species in the county of Norfolk, the first formal conservation designation for the species in the U.K. The C. carassius BAP plan aims to halt the decline of this much overlooked species through reintroductions and selective stocking of suitable ponds within the native range of the species.

Experimental study of carbon sequestration reactions controlled by the percolation of CO2-rich brine through peridotites.

Carbonation of ultramafic rocks in geological reservoirs is, in theory, the most efficient way to trap CO2 irreversibly; however, possible feedback effects between carbonation reactions and changes in the reservoir permeability must be considered to realistically assess the efficiency and sustainability of this process. We investigated changes in the hydrodynamic properties of sintered dunite samples by means of percolation experiments, under conditions analogous to that of in situ carbonation. Our results show that carbonation efficiency is controlled by the local renewal of the reactants and the heterogeneity of the pore structure. Preferential flow zones are characterized by the formation of magnetite and of a silica-rich layer at the olivine surfaces, which eventually inhibits olivine dissolution. Conversely, sustainable olivine dissolution together with coprecipitation of magnesite, siderite, and minor Mg-TOT-phyllosilicates, occur in reduced-flow zones. Thus carbonate precipitation only decreases porosity in zones where diffusion-controlled transport is dominant. Consequently, while high flow rates will decrease the carbonation efficiency of the reservoir and low flow rates may reduce the permeability irreversibly close to the injection point, moderate injection rates will ensure a partial carbonation of the rock and maintain the reservoir permeability.

[Value of a clinical test for assessing physical activity in children]. / Valor de un test clínico para evaluar actividad física en niños.

BACKGROUND: An appropriate measurement of physical activity (PA) in children is useful, since inactivity is associated to obesity, cardiovascular and metabolic risk. AIM: To assess the reliability of the INTA questionnaire of PA, to compare the derived PA score with accelerometry and to assess its ability to identify excessively inactive children. MATERIAL AND METHODS: One hundred eighty children aged 8 to 13 years answered an interviewer-administered questionnaire about their usual PA, consisting in 5 items (recumbent, seated, walking, playing outdoor, sports). The answers were converted to a PA score with a 0-10 points scale. Reliability was tested in 87 children by test/retest conducted 3-5 days apart. The PA score was compared with 3-day accelerometry in 77 of 93 children (35 obese and 42 non obese). Receiver operating characteristic (ROC) curves were used to determine the optimal cut-point for identify an excessively sedentary child. RESULTS: The test/retest reliability of the questionnaire was 0.69 to 0.93 (Lin coefficient). Accelerometry was significantly associated with PA score (RHO: 0.60, p =0.008), outdoor plays (RHO: 0.37, p =0.0009) and practicing of sports (RHO: 0.33, p =0.003). Obese children were less active than non obese children, according both to PA score and to accelerometry. The optimal cut-point for classifying a child as too sedentary was a score of 5 (sensitivity =0.89). CONCLUSIONS: The INTA-test is a valuable instrument for measuring usual PA in clinical practice and is easy to administer.

[Transfusion in elderly patients]. / Transfusion chez les patients âgés.

The frequency of anemia is responsible of a frequent use of transfusion in elderly patients. However, transfusion in elderly patients requires several warnings. First, semiology of elderly patients is characterized with atypical clinical signs, and anemia tolerance is often difficult to appreciate. Second, numerous comorbidities make of elderly patients an heterogeneous population, in which guidelines are poorly applicable. Last, elderly patients are particularly sensitive to iatrogenic events, and the haemodynamic overload related to transfusion has to be carefully managed. All these difficulties raise the need of prospective studies on transfusion in elderly patients to validate clinical practice.

Valor de un test clínico para evaluar actividad física en niños / Value of a clinical test for assessing physical activity in children

Background: An appropriate measurement of physical activity (PA) in children is useful, since inactivity is associated to obesity, cardiovascular and metabolic risk. Aim: To assess the reliability of the INTA questionnaire of PA, to compare the derived PA score with accelerometry and to assess its ability to identify excessively inactive children. Material and methods: One hundred eighty children aged 8 to 13 years answered an interviewer-administered questionnaire about their usual PA, consisting in 5 items (recumbent, seated, walking, playing outdoor, sports). The answers were converted to a PA score with a 0-10 points scale. Reliability was tested in 87 children by test/retest conducted 3-5 days apart. The PA score was compared with 3-day accelerometry in 77 of 93 children (35 obese and 42 non obese). Receiver operating characteristic (ROC) curves were used to determine the optimal cut-point for identify an excessively sedentary child. Results: The test/retest reliability of the questionnaire was 0.69 to 0.93 (Lin coefficient). Accelerometry was significantly associated with PA score (RHO: 0.60, p =0.008), outdoor plays (RHO: 0.37, p =0.0009) and practicing of sports (RHO: 0.33, p =0.003). Obese children were less active than non obese children, according both to PA score and to accelerometry. The optimal cut-point for classifying a child as too sedentary was a score of 5 (sensitivity =0.89). Conclusions: The INTA-test is a valuable instrument for measuring usual PA in clinical practice and is easy to administer.

[Hemophagocytic syndrome and toxoplasmic primo-infection]. / Syndrome d'activation macrophagique et primo-infection toxoplasmique.

Hemophagocytic syndrome (HPS) is a clinical entity that combines the clinical, biological and histological symptoms. The physiopathological mechanism involves the interaction between T lymphocytes/NK cells and macrophages, at the origin of an uncontrolled activation of the macrophages. The consequence is a hemophagocytosis extending to numerous organs, preferentially bone marrow. Clinical symptoms include cytopenia, fever unresponsive to antibiotics and multiple organ dysfunctions. Infections, lymphoproliferative disorders, cancers, systemic diseases are the most prevalent triggers or etiologies of HPS. Because of its high risk of mortality, HPS constitutes a diagnostic and therapeutic urgency. The search for an aetiology, in particular by serological testing, is essential because it conditions the treatment and thus the evolution of the disease. We report here the case of a 12 years-old boy presenting a HPS secondary to a toxoplasmic primo-infection. The objective of this work is to present the step of the biological diagnosis of HPS. Moreover, this observation allows the study of a very rare clinical presentation of toxoplasmic primo-infection, in an immunocompetant patient.

[Removal of a tracheostomy in ventilator-dependent patients with neuromuscular disease]. / Sevrage de la trachéotomie chez des patients neuromusculaires dépendants d'une ventilation mécanique.

BACKGROUND: Ventilation via a tracheostomy is effective but very restricting in patients with neuromuscular disease. Return to non-invasive ventilation (NIV) is possible but this is not common practice, partly for want of standardised procedures ensuring a safe transition. METHODS: A procedure for transfer of ventilation via a tracheostomy to a mask has been developed based on the literature and local experience (feasibility of NIV, absence of laryngo-tracheal lesions, adequate leak compensation, effective cough). It has been tested in three patients with severe but stable neuromuscular disorders (chronic polyneuropathy in two cases and progressive spinal amyotrophy on one). RESULTS: The three patients were able to be extubated and established on domiciliary ventilation in 6,7 and 10 days, at the end of which all were discharged home. After 4 months in two cases and 6 months in the other no significant complications developed, the respiratory status under NIV was comparable to that previously under tracheostomy and the patients were satisfied with the change. CONCLUSION: The proposed algorithm seems to permit a rapid and safe transition from a tracheostomy to a mask. Large scale studies are needed to verify this concept and subsequently to identify within which group a similar approach may be correctly applied.

Alterations in single muscle fiber calcium sensitivity with resistance training in older women.

The purpose of this investigation was to determine the effects of a 12-week progressive resistance-training program (PRT) on single muscle fiber calcium sensitivity in six older women (73 +/- 2 years). Muscle biopsy samples of the vastus lateralis were obtained pre- and post-PRT. Chemically skinned single muscle fibers ( n=274) were dissected and studied. The experimental sequence for each fiber was the determination of peak maximal isometric tension ( P(o)) at pCa 4.5 (pCa=-log[Ca(2+)]), and then subsequent submaximal activations of the fiber at nine Ca(2+) concentrations (pCa 6.8 to 4.7). Myosin heavy chain (MHC) I fiber (slow-twitch) diameter increased 16% ( P<0.05) with no change in MHC IIa fibers (fast-twitch) pre- to post-PRT, respectively. P(o) in MHC I fibers increased 34% ( P<0.05) as a result of the training with no change in MHC IIa fibers. The mean MHC I Ca(2+) activation threshold (minimal amount of Ca(2+) necessary to induce tension) increased from 6.83 +/- 0.02 to 6.91 +/- 0.01 ( P<0.05), as did the mean half-maximal activation (pCa(50)), 5.51 +/- 0.02 to 5.71 +/- 0.03 ( P<0.05) with PRT. The slope of the Hill plot above ( n(1)) the pCa(50) for MHC I did not change significantly with the PRT. However, the slope of the Hill plot below ( n(2)) the pCa(50) for MHC I demonstrated an increase ( P<0.05) with training. There were no differences with MHC IIa fibers with PRT for any of the variables measured. In conclusion, the results of this investigation indicate that myofibril Ca(2+) sensitivity and activation properties are altered in MHC I, but not MHC IIa fibers with PRT in older women. The alterations in the MHC I Ca(2+) properties appear to have an effect on the mechanisms involved with skeletal muscle adaptability in older women following PRT.

Resistance training improves single muscle fiber contractile function in older women.

The purpose of this study was to 1) examine single cell contractile mechanics of skeletal muscle before and after 12 wk of progressive resistance training (PRT) in older women (n = 7; 74 +/- 2 yr) and 2) to compare these results to our previously completed single cell PRT work with older men (n = 7; 74 +/- 2 yr) (Trappe S, Williamson D, Godard M, Porter D, Rowden G, and Costill D. J Applied Physiol 89:143--152, 2000). Knee extensor PRT was performed 3 days/wk at 80% of one-repetition maximum. Muscle biopsies were obtained from the vastus lateralis before and after the PRT. Chemically skinned single muscle fibers (n = 313) were studied at 15 degrees C for peak tension (P(o)), unloaded shortening velocity (V(o)), and power. Due to the low number of hybrid fibers identified post-PRT, direct comparisons were limited to MHC I and IIa fibers. Muscle fiber diameter increased 24% (90 +/- 2 to 112 +/- 6 microm; P < 0.05) in MHC I fibers with no change in MHC IIa fibers. P(o) increased (P < 0.05) 33% in MHC I (0.76 +/- 0.04 to 1.01 +/- 0.09 mN) and 14% in MHC IIa (0.73 +/- 0.04 to 0.83 +/- 0.05 mN) fibers. Muscle fiber V(o) was unaltered in both fiber types with PRT. MHC I and IIa fiber power increased (P < 0.05) 50% [11 +/- 2 to 17 +/- 2 microN. fiber length (FL). s(-1)] and 25% (40 +/- 8 to 51 +/- 6 microN. FL. s(-1)), respectively. However, when peak power was normalized to cell size, no pre- to postimprovements were observed. These data indicate that PRT in elderly women increases muscle cell size, strength, and peak power in both slow and fast muscle fibers, which was similar to the older men. However, in contrast to the older men, no change in fiber V(o) or normalized power was observed in the older women. These data suggest that older men and women respond differently at the muscle cell level to the same resistance-training stimulus.

Beta-hydroxy-beta-methylbutyrate ingestion, Part I: effects on strength and fat free mass.

PURPOSE: The purpose of this investigation was 1) to determine whether HMB supplementation results in an increase in strength and FFM during 8 wk of resistance training and 2) determine whether a higher dose of HMB provides additional benefits. METHODS: Thirty-seven, untrained, college-aged men were assigned to one of three groups: 0, 38, or 76 mg x kg(-1) x d(-1) of HMB (approximately equal to 3 and 6 g x d(-1), respectively). Resistance training consisted of 10 different exercises performed 3 d x wk(-1) for 8 wk at 80% of 1-repetition maximum (1RM). The 1RM was reevaluated every 2 wk with workloads adjusted accordingly. RESULTS: No differences were observed in 1RM strength among the groups at any time. However, the 38 mg x kg (-1) x d(-1) group showed a greater increase in peak isometric torque than the 0 or 76 mg.kg(-1) x d(-1) groups (P < 0.05). The 76 mg x kg(-1) x d(-1) group had a greater increase in peak isokinetic torque than the 0 or 38 mg x kg(-1) x d(-1) groups at 2.1, -3.15, and -4.2 rad x s(-1) (P < 0.05). Plasma creatine phosphokinase (CPK) activity was greater for the 0 mg x kg(-1) x d(-1) versus the 38 or 76 mg x kg(-1) x d(-1) groups at 48 h after the initial training bout (P < 0.05). In addition, no differences were observed in body fat between the three groups. However, the 38 mg x kg(-1) x d(-1) group exhibited a greater increase in FFM (P < 0.05). CONCLUSIONS: Although the IRM strength gains were not significantly different, HMB supplementation appears to increase peak isometric and various isokinetic torque values, and increase FFM and decrease plasma CPK activity. Lastly, it appears that higher doses of HMB (i.e., > 38 mg x kg(-1) x d(-1)) do not promote strength or FFM gains.

Beta-hydroxy-beta-methylbutyrate ingestion, part II: effects on hematology, hepatic and renal function.

PURPOSE: The purpose of this investigation was to examine the effects of differing amounts of beta-hydroxy-beta-methylbutyrate (HMB), 0, 36, and 76 mg x kg(-1) x d(-1), on hematology, hepatic and renal function during 8 wk of resistance training. METHODS: Thirty-seven, untrained collegiate males and were randomly assigned to one of the three groups, 0, 38, or 76 mg x kg(-1) x d(-1). Resistance training consisted of 10 exercises, performed 3 d x wk(-1) for 8 wk at 80% of their 1-repetition maximum. Blood and urine was obtained before training, 48 h after the initial session, 1 wk, 2 wk, 4 wk, and at 8 wk of resistance training. Blood was analyzed for glucose, blood urea nitrogen, hemoglobin, hepatic enzymes, lipid profile, total leukocytes, and individual leukocytes. Urine was analyzed for pH, glucose, and protein excretion. RESULTS: The 38 mg x kg(-1) x d(-1) group had a greater increase in basophils compared with 0 or 76 mg x kg(-1) x d(-1) groups (P < 0.05). No difference occurred in any other blood and urine measurements. CONCLUSION: These data indicate that 8 wk of HMB supplementation (< or = 76 mg x kg(-1) x d(-1)) during resistance training had no adverse affects on hepatic enzyme function, lipid profile, renal function, or the immune system.

Effect of resistance training on single muscle fiber contractile function in older men.

The purpose of this study was to examine single cell contractile mechanics of skeletal muscle before and after 12 wk of progressive resistance training (PRT) in older men (n = 7; age = 74 +/- 2 yr and weight = 75 +/- 5 kg). Knee extensor PRT was performed 3 days/wk at 80% of one-repetition maximum. Muscle biopsy samples were obtained from the vastus lateralis before and after PRT (pre- and post-PRT, respectively). For analysis, chemically skinned single muscle fibers were studied at 15 degrees C for peak tension [the maximal isometric force (P(o))], unloaded shortening velocity (V(o)), and force-velocity parameters. In this study, a total of 199 (89 pre- and 110 post-PRT) myosin heavy chain (MHC) I and 99 (55 pre- and 44 post-PRT) MHC IIa fibers were reported. Because of the minimal number of hybrid fibers identified post-PRT, direct comparisons were limited to MHC I and IIa fibers. Muscle fiber diameter increased 20% (83 +/- 1 to 100 +/- 1 microm) and 13% (86 +/- 1 to 97 +/- 2 microm) in MHC I and IIa fibers, respectively (P < 0.05). P(o) was higher (P < 0.05) in MHC I (0.58 +/- 0.02 to 0.90 +/- 0.02 mN) and IIa (0.68 +/- 0.02 to 0.85 +/- 0.03 mN) fibers. Muscle fiber V(o) was elevated 75% (MHC I) and 45% (MHC IIa) after PRT (P < 0.05). MHC I and IIa fiber power increased (P < 0.05) from 7.7 +/- 0.5 to 17.6 +/- 0.9 microN. fiber lengths. s(-1) and from 25.5 to 41.1 microN. fiber lengths. s(-1), respectively. These data indicate that PRT in elderly men increases muscle cell size, strength, contractile velocity, and power in both slow- and fast-twitch muscle fibers. However, it appears that these changes are more pronounced in the MHC I muscle fibers.

Effects of postexercise carbohydrate-protein feedings on muscle glycogen restoration.

The purpose of this investigation was to determine the effects of postexercise eucaloric carbohydrate-protein feedings on muscle glycogen restoration after an exhaustive cycle ergometer exercise bout. Seven male collegiate cyclists [age = 25.6 +/- 1.3 yr, height = 180.9 +/- 3.2 cm, wt = 75.4 +/- 4.0 kg, peak oxygen uptake (VO(2 peak)) = 4.20 +/- 0.2 l/min] performed three trials, each separated by 1 wk: 1) 100% alpha-D-glucose [carbohydrate (CHO)], 2) 70% carbohydrate-20% protein (PRO)-10% fat, and 3) 86% carbohydrate-14% amino acid (AA). All feedings were eucaloric, based on 1.0 g. kg body wt(-1). h(-1) of CHO, and administered every 30 min during a 4-h muscle glycogen restoration period in an 18% wt/vol solution. Muscle biopsies were obtained immediately and 4 h after exercise. Blood samples were drawn immediately after the exercise bout and every 0.5 h for 4 h during the restoration period. Increases in muscle glycogen concentrations for the three feedings (CHO, CHO-PRO, CHO-AA) were 118 mmol/kg dry wt; however, no differences among the feedings were apparent. The serum glucose and insulin responses did not differ throughout the restoration period among the three feedings. These results suggest that muscle glycogen restoration does not appear to be enhanced with the addition of proteins or amino acids to an eucaloric CHO feeding after exhaustive cycle exercise.

An upper arm model for simulated weightlessness.

This investigation examined the effects of 4 weeks of non-dominant arm unloading on the functional and structural characteristics of the triceps brachii muscle of six normo-active college-age males (age: 23 +/- 1 years, height: 176 +/- 4 cm, weight: 76 +/- 6 kg). The primary intention of this study was to determine if arm unloading is an effective analogue for simulating the effects of weightlessness on human skeletal muscle. Subjects were tested 2-3 days preceding unloading in a standard arm sling and following removal of the sling. The sling was worn during waking hours to unload the arm. Subjects were allowed to remove the sling during sleep and bathing. Torque production (Nm) during maximal isometric extension at 90 degrees significantly declined (P < 0.05) in response to unloading (53.93 +/- 5.07 to 47.90 +/- 5.92; 12%). There was no significant change (P > 0.05) in the force-velocity attributes of the triceps over the other measured velocities (1.05, 1.57, 2.09, 3.14, 4.19, 5.24 rad.s-1). Cross-sectional muscle area (CSA) of the upper arm was smaller (44.3 +/- 2.7 to 42.4 +/- 2.5 cm2; 4%) following 4 weeks of unloading (P < 0.05). Histochemical analysis of individual muscle fibres demonstrated reductions in fibre CSA of 27 and 18% for type I and type II fibres, respectively. However, these changes were not statistically significant. Electrophoretic analysis of muscle samples revealed a significant increase (40 +/- 7 to 58 +/- 4%, pre- and post-, respectively) in myosin heavy chain (MHC) type II isoforms following unloading. Reductions in type I MHC isoform composition failed to reach statistical significance (P < 0.08). Amplitude of the integrated electromyographic (IEMG) signal during maximal isometric contraction of the long head of the triceps decreased by 21% in response to the 4-week unloading period (P < 0.05). The changes in triceps, muscle structure and function found with arm unloading are similar in magnitude and direction to data obtained from humans following exposure to real and simulated weightlessness. These findings demonstrate that arm unloading produces some of the effects seen in response to weightlessness in muscles of the upper arm and provides potential for an additional model to simulate the effects of microgravity on human skeletal muscle.

[Coinfection with HIV and HTLV-I infection and survival in AIDS stage. French Guiana Study. GECVIG (Clinical HIV Study Group in Guiana)]. / Co-infection par VIH et HTLVI et survie au stade SIDA. Etude en Guyane Française. GECVIG (Groupe d'Etudes cliniques du VIH en Guyane).

OBJECTIVE: The purpose of this study was to investigate the effect of HTLVI infection on survival in AIDS patients in French Guiana. PATIENTS AND METHODS: A cohort of 151 adult patients with AIDS were followed from January 1992 through June 1996. Kaplan-Meier survival curves were established. Using the Cox model, multivariate analysis was performed to examine different factors affecting survival. RESULTS: The incidence of HTLVI infection in this cohort was 11.9% and 57.6% of the patients died during the study period. Multivariate analysis disclosed that older age at diagnosis of AIDS (over 45 years) and low CD4 count (< 100/mm3) were predictors of poor survival. HIV-HTLVI co-infection was strongly correlated with reduced survival (p = 0.02; RR = 2.2; CI = 1.1-4.5). CONCLUSION: In our region, all patients with HIV infection should be screened for HTLVI infection. In case of co-infection, early care should included adapted antiretroviral regimens.

Progressive resistance training reduces myosin heavy chain coexpression in single muscle fibers from older men.

The purpose of this study was to examine myosin heavy chain (MHC) and myosin light chain (MLC) isoforms following 12 wk of progressive resistance training (PRT). A needle biopsy was taken from the vastus lateralis to determine fiber-type expression [ATPase (pH 4.54) and MHC/MLC] in seven healthy men (age = 74.0 +/- 1.8 yr). Subjects were also tested for 1-repetition maximum (1-RM), pre- and posttraining. The progressive knee extensor protocol consisted of three sets at 80% of 1-RM 3 days/wk for 12 wk. Freeze-dried, single muscle fibers were dissected for MHC and MLC analysis and then subjected to SDS-PAGE and silver staining, pre- and posttraining. MHC expression increased in the I (10.4%; P < 0.05) and decreased in I/IIa (9.0%; P < 0.05), I/IIa/x (0.9%; P < 0.05), and IIa/x (8.9%; P < 0.05) isoforms, with no change in the IIa and IIx isoforms, pre- vs. posttraining (total fibers = 3,059). The MLC(3f)-to-MLC(2) ratio did not change with the PRT in either the MHC I or MHC IIa isoforms (total fibers = 902), pre- to posttraining. ATPase fiber distribution did not significantly differ following training (I: 50. 4 +/- 6.7 vs. 51.9 +/- 7.9, IIa: 36.8 +/- 5.3 vs. 41.1 +/- 7.0, IIb: 12.8 +/- 5.6 vs. 7.0 +/- 4.0%; pre- vs. posttraining, respectively). 1-RM increased (51.9%; P < 0.05) from pre- to posttraining. The PRT provide a stimulus for alterations in MHC isoforms, which demonstrated a decrease in all hybrid isoforms and an increase in MHC I expression (not found in the ATPase results), unlike the MLC ratio (3:2), which was not altered with training.