The purpose of this study was to investigate whether creatine (Cr) supplementation during 12 weeks of phasic high-frequency voluntary wheel running would result in a faster myosin heavy chain (MHC) isoform profile in the rat mixed fast-twitch plantaris and alter its corresponding isometric contractile properties. The fast-twitch extensor digitorum longus and medial gastrocnemius and slow-twitch soleus were also studied. Forty weanling Sprague-Dawley male rats were assigned to one of four groups: creatine-sedentary (Cre-Sed); creatine-voluntary running (Cre-Run); control-sedentary (Con-Sed); control-voluntary running (Con-Run). Daily running distance was similar between Cre-Run and Con-Run. Average daily Cr ingestion was also similar being 2.4+/-0.17 and 3.0+/-0.14 g/kg in Cre-Sed and Cre-Run, respectively. Total creatine (TCr) content was elevated (P<0.03) in the plantaris of Cre-Run [211.4+/-16.9 mmol/kg dry weight (dw)], compared with Con-Run (175.1+/-5.69). In the plantaris, MHCIIb was 13% greater (P<0.00001) in Cre-Run compared with Con-Run, while MHCIId/x and MHCIIa were lower in Cre-Run by 7 and 6% (P<0.0002), respectively. No differences were observed in twitch force, time-to-peak tension, half-rise time or half-fall time. Greater tetanic force production (P<0.05) in Cre-Sed compared with Con-Sed corresponded to a 12% increase in MHCIId/x (P<0.0001) and a 12% decrease in MHCIIb (P<0.0006). The fatigue index of the plantaris at 10 s (FI(10s)) was reduced only after running (Cre-Run vs Con-Run), while in all other muscles the FI(10s) was lower only in the Cre-Sed group. In conclusion, Cr supplementation had differential effects on MHC isoform content and fatigability that depended on the level of contractile activity. Cr feeding combined with running exercise resulted in a faster MHC-based phenotype in the rat plantaris but the impact on associated isometric contractile properties was minimal.
We investigated the effects of chronic creatine loading and voluntary running (Run) on muscle fiber types, proteins that regulate intracellular Ca2+, and the metabolic profile in rat plantaris muscle to ascertain the bases for our previous observations that creatine loading results in a higher proportion of myosin heavy chain (MHC) IIb, without corresponding changes in contractile properties. Forty Sprague-Dawley rats were assigned to one of four groups: creatine-fed sedentary, creatine-fed run-trained, control-fed sedentary, and control-fed run-trained animals. Proportion and cross-sectional area increased 10% and 15% in type IIb fibers and the proportion of type IIa fibers decreased 11% in the creatine-fed run-trained compared with the control-fed run-trained group (P < 0.03). No differences were observed in fast Ca2+-ATPase isoform SERCA1 content (P > 0.49). Creatine feeding alone induced a 41% increase (P < 0.03) in slow Ca2+-ATPase (SERCA2) content, which was further elevated by 33% with running (P < 0.02). Run training alone reduced parvalbumin content by 50% (P < 0.05). By comparison, parvalbumin content was dramatically decreased by 75% (P < 0.01) by creatine feeding alone but was not further reduced by run training. These adaptive changes indicate that elevating the capacity for high-energy phosphate shuttling, through creatine loading, alleviates the need for intracellular Ca2+ buffering by parvalbumin and increases the efficiency of Ca2+ uptake by SERCAs. Citrate synthase and 3-hydroxyacyl-CoA dehydrogenase activities were elevated by run training (P < 0.003) but not by run training + creatine feeding. This indicates that creatine loading during run training supports a faster muscle phenotype that is adequately supported by the existing glycolytic potential, without changes in the capacity for terminal substrate oxidation.
FUNDAMENTOS: A integração das ações de controle da hanseníase às estratégias dos Programas de Saúde da Família e Agentes Comunitários de Saúde, na conformidade do processo de reorganização da atenção básica, fundamentou a atualização das normas da legislação sobre o controle da doença no Brasil. A classificação operacional adotada, para alocação do paciente na poliquimioterapia, foi adaptada da sugerida pela Organização Mundial de Saúde, essencialmente clínica, baseada no número de lesões cutâneas. De acordo com essa recomendação, são considerados paucibacilares (PB) os casos com até cinco lesões e multibacilares (MB) os com mais de cinco lesões cutâneas.O que se discute é a validade desse método de classificação, que toma como referência apenas aspectos clínicos. OBJETIVOS: Avaliar o método clínico de classificação baseado no número de lesões cutâneas correlacionando-o com os resultados dos exames baciloscópicos de esfregaços da pele. MÉTODOS: A fonte de informações foi o banco de dados no qual são registradas informações clínicas, epidemiológicas e laboratoriais dos pacientes. Foram selecionados 837 registros do período de 1986 a 1999, e os critérios avaliados foram o número de lesões cutâneas e o resultado do exame baciloscópico, ambos no momento do diagnóstico. Estabeleceu-se a comparação e calcularam-se a sensibilidade e especificidade relativa e os valores preditivo positivo e negativo do critério lesão cutânea e determinou-se a concordância entre o número de lesões e a baciloscopia por meio do cálculo do índice Kappa (k). RESULTADOS: Dos 837 casos avaliados, 652 apresentavam baciloscopias positivas, e 185, negativas. Dos positivos, 68 (11.4%) apresentavam menos de cinco lesões, e dos negativos 30 (16.0%) apresentavam mais de cinco lesões cutâneas. A sensibilidade e a especificidade do critério clínico foram de 89.6% e de 83.8% respectivamente, e o valor preditivo positivo de 95.1%, e o negativo de 69.5%. CONCLUSÃO: o método clínico baseado no número de lesões cutâneas para classificação dos pacientes hansenianos apresenta limitações que não invalidam sua operacionalidade, porém novos critérios devem ser desenvolvidos possibilitando uma melhor acurácia na alocação dos pacientes nos esquemas poliquimioterápicos.
Leprosy (Hansen's disease, HD) reactions are immune-inflammatory phenomena that occur during the evolution of the disease. Given the current criteria for treatment of the disease, this event is often observed after the patient has been released from treatment (RFT) from multi-drug therapy (MDT). A case-control study was conducted comparing laboratory results of cases of leprosy reactions after RFT from multibacillary MDT (MDT/MB) with a control group to analyze the possible association between posttreatment reactions and bacterial load using the ML Flow serological test for detection of antibodies to Mycobacterium leprae and the results of bacilloscopic skin smears. The study was conducted in two reference centers in Recife, Pernambuco State, Brazil, involving 208 patients. The results obtained indicate that posttreatment reaction is statistically associated with bacterial load through positive serology post-RFT. In conclusion, common risk factors exist between relapses and post-RFT reactions.
activated protein kinase (AMPK) signaling initiates adaptive changes in skeletal muscle fibers that restore homeostatic energy balance. The purpose of this investigation was to examine, in rats, the fiber-type protein expression patterns of the ␣-catalytic subunit isoforms in various skeletal muscles, and changes in their respective contents within the tibialis anterior (TA) after chronic low-frequency electrical stimulation (CLFS; 10 Hz, 10 h daily), applied for 4 Ϯ 1.2 or 25 Ϯ 4.8 days. Immunocytochemical staining of soleus (SOL) and medial gastrocnemius (MG) showed that 86 Ϯ 4.1 to 97 Ϯ 1.4% of type IIA fibers stained for both the ␣1-and ␣2-isoforms progressively decreased to 63 Ϯ 12.2% of type IID/X and 9 Ϯ 2.4% of IIB fibers. 39 Ϯ 11.4% of IID/X and 83 Ϯ 7.9% of IIB fibers expressed only the ␣2 isoform in the MG, much of which was localized within nuclei. ␣1 and ␣2 contents, assessed by immunoblot, were lowest in the white gastrocnemius [WG; 80% myosin heavy chain (MHC) IIb; 20% MHCIId/x]. Compared with the WG, ␣1 content was 1.6 Ϯ 0.08 (P Ͻ 0.001) and 1.8 Ϯ 0.04 (P Ͻ 0.0001)-fold greater in the red gastrocnemius (RG: 13%, MHCIIa) and SOL (21%, MHCIIa), respectively, and increased in proportion to MHCIIa content. Similarly, ␣2 content was 1.4 Ϯ 0.10 (P Ͻ 0.02) and 1.5 Ϯ 0.07 (P Ͻ 0.001)-fold greater in RG and SOL compared with WG. CLFS induced 1.43 Ϯ 0.13 (P Ͻ 0.007) and 1.33 Ϯ 0.08 (P Ͻ 0.009)-fold increases in the ␣1 and ␣2 contents of the TA and coincided with the transition of faster type IIB and IID/X fibers toward IIA fibers. These findings indicate that fiber types differ with regard to their capacity for AMPK signaling and that this potential is increased by CLFS. myosin heavy chain; fast-twitch muscle; slow-twitch muscle 5Ј-AMP-ACTIVATED PROTEIN KINASE (AMPK) is a heterotrimeric serine/threonine kinase comprising an ␣ catalytic subunit (␣1 or ␣2), and noncatalytic  (1 or 2) and ␥ (␥1, ␥2, or ␥3) subunits (12,41). This enzyme complex is the central component of a signaling cascade in skeletal muscle that serves as an intracellular energy-sensor by detecting decreases in the intracellular energy potential (i.e., ATP/ADP free ) through related increases in AMP (11,13,26). Being highly sensitive to small reductions in ATP and corresponding increases in AMP (25), AMPK is activated in skeletal muscle during contractile activity (32, 68, 69) to acutely restore energy balance by increasing flux through ATP-generating pathways (24, 25).In contrast, chronic AMPK activation induced by pharmacological agonists (3, 29, 58, 71) regulates long-term adaptive changes similar to exercise training that seem to limit future reductions in the intracellular energy potential and reportedly reduce metabolic disturbances in rats displaying skeletal muscle insulin resistance (9,52,70). Prolonged AMPK activation has, for example, been associated with mitochondrial genesis (3,58,71,74) and greater expression levels of genes involved in glucose uptake and storage (3, 9, 29), as well as lower plasma free fatty acid and trigl...
We performed genotyping of Mycobacterium leprae present in skin biopsy samples that were collected during the first and the second disease occurrences from eight leprosy patients, seven of whom were diagnosed as suffering from disease relapse. Sequence analysis of part of the M. leprae rpoB, folP1, gyrB and gyrA genes did not show genetic change that supported the presence of drug-resistant bacilli. However, we observed a synonymous nucleotide change at position 297 of gyrA among five of these patients, one presenting C to T (CgyrAT) and four presenting T to C (TgyrAC) at this position. Additional genotyping by analysis of the four short tandem repeats GAA, GTA9, AT17 and TA18 showed that the gyrA single nucleotide polymorphism change was accompanied by a change in short tandem repeat genotype. Our data suggest that leprosy relapse in these patients, living in an area endemic for leprosy, could be caused by M. leprae with a genotype different from the one that caused initial disease.
The present study investigated the absolute reliability (R Ab ) of isometric measures of time-topeak tension (TTP), half-rise time (
FUNDAMENTOS: Estudos sobre os pacientes hansenianos retratados justificam-se pela dificuldade do diagnóstico diferencial entre quadro reacional após alta do tratamento específico de hanseníase e recidiva, devido às limitações de critérios clínicos e laboratoriais para diferenciá-los. OBJETIVOS: Verificar os procedimentos diagnósticos clínicos e laboratoriais que subsidiaram o retratamento por recidiva e a ocorrência de episódios reacionais, em especial os que ocorreram após o término do tratamento. MÉTODOS: Mediante o estudo retrospectivo de série de casos foram estudados 155 pacientes hansenianos retratados por recidiva em duas unidades de referência em hanseníase, no município de Recife/PE, Brasil. RESULTADOS: O critério clínico foi o mais utilizado para a decisão de retratamento por recidiva, e as lesões novas descritas foram principalmente do tipo mácula e infiltração. Os episódios reacionais após alta ocorreram em 34% desses pacientes, e 33,9% relatavam a presença de comunicantes com hanseníase. Dos 155 pacientes estudados apenas 14,9% realizaram exame histológico e 18,1% não realizaram a baciloscopia antes de reiniciar a terapia específica. CONCLUSÃO: Este estudo evidenciou que os episódios reacionais após o tratamento e a presença de comunicantes com hanseníase ocorreram em torno de 30% nos pacientes retratados por recidiva e que se fazem necessários outros estudos controlados para o melhor entendimento desses fatores.
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