Apparently increased trough levels of tacrolimus caused by acute infantile diarrhea in two infants with biliary atresia after liver transplantation

Two infants with biliary atresia who exhibited three-fold increased trough levels of tacrolimus and required reduced doses during episodes of acute infantile diarrhea within 5 months of liver transplantation are described. The cause of the increase was not explained simply by hemoconcentration as a result of significant loss of extracellular fluid during these episodes. It does highlight an important issue: that of the continuing need to carefully monitor the trough levels of tacrolimus in such infants.     

Neuromuscular function and mechanical efficiency of human leg extensor muscles during jumping exercises

The influence of prestretch amplitude on the mechanical efficiency was examined with 5 subjects, who performed 5 different series of vertical jumps, each of which differed with respect to the mechanics of the knee joint action during the prestretch (eccentric) phase of the contact on the floor. Electromyographic activity was recorded from the major extensor muscles during the entire work period of 1 min per series. In addition, expired air was collected during the test and recovery for determination of energy expenditure. Mechanical work was calculated from the vertical displacement of the body during the jumps. The results indicated that high net efficiency of 38.7% was observed in condition where amplitude of knee bending in eccentric phase was small. In large range motion the corresponding net efficiency was 30.1%. In jumps where no prestretching of extensor muscles ocurred the net efficiency was 19.7%. The high efficiency of small amplitude jumps was characterized by low myoelectrical activity of the leg extensor muscles during the positive (concentric) work phase. In addition, the small amplitude jumps had shorter transition time in the stretch-shortening cycle, high average eccentric force and high stretching speed. Therefore the results suggest that the restitution of elastic energy, which was also related to the length change and stiffness of the muscles during stretch, plays an important role in regulating the mechanical efficiency of work.     

Changes in isometric force- and relaxation-time,electromyographic and muscle fibre characteristics of human skeletal muscle during strength training and detraining

HÄKKINEN, K., ALÉN, M. & KOMI, P.V. 1985. Changes in isometric force- and relaxation-time, electromyographic and muscle fibre characteristics of human skeletal muscle during strength training and detraining. Acta Physiol Scand 125, 573–585. Received 26 January 1985, accepted 9 May 1985. ISSN 0001–6772. Department of Biology of Physical Activity and Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland. Eleven male subjects (20–32 years) accustomed to strength training went through progressive, high-load strength training for 24 weeks with intensities ranging variably between 70 and 120% during each month. This training was also followed by a 12-week detraining period. An increase of 26.8% (P < 0.001) in maximal isometric strength took place during the training. The increase in strength correlated (P < 0.05) with significant (P < 0.05–0.01) increases in the neural activation (IEMG) of the leg extensor muscles during the most intensive training months. During the lower-intensity training, maximum IEMG decreased (P < 0.05). Enlargements of muscle-fibre areas, especially of fast-twitch type (P < 0.001), took place during the first 12 weeks of training. No hypertrophic changes were noted during the latter half of training. After initial improvements (P < 0.05) no changes or even slight worsening were noted in selected force-time parameters during later strength training. During detraining a great (P < 0.01) decrease in maximal strength was correlated (P < 0.05) with the decrease (P < 0.05) in the maximum IEMGs of the leg extensors. This period resulted also in decreases (P < 0.05) of the mean muscle-fibre areas of both fibre types. It was concluded that improvement in strength may be accounted for by neural factors during the course of very intensive strength training. Selective training-induced hypertrophy also contributed to strength development but muscle hypertrophy may have some limitations during long-lasting strength training, especially in highly trained subjects.     

Stimulation of Prostaglandin Production by Quinolone Phototoxicity in Balb/c 3T3 Mouse Fibroblast Cells in Vitro

Sparfloxacin (SPFX) and levofloxacin (LVFX) with ultraviolet-A(UVA) irradiation have been reported to induce skin inflammationdue to phototoxicity in Balb/c mice. We examined the productionof arachidonic acid metabolites induced by quinolone phototoxicityin Balb/c 3T3 mouse fibroblast cells in vitro. The cells weresimultaneously treated with SPFX or LVFX at 1,10, or 100 µMand UVA irradiation for 5 min (0.5 J/cm²). They were then culturedin quinolone-free medium for 24 hr, and the concentrations ofprostaglandin E₂ (PGE₂ 6-ketoprostaglandin F₁ (6-keto-PGF₁),and leukotriene B₄ (LTB₄) in the incubation medium were measured.Furthermore, the effect of quinolone photoproducts on the productionof the inflammatory mediators and that of indomethacin on PGE₂level were also examined. Treatment with SPFX at 100 µMplus UVA irradiation markedly increased levels of PGE₂ and 6-keto-PGF₁but not that of LTB SPFX or LVFX alone at up to 100 µM,100 µM SPFX, or 100µM LVFX, or less plus UVA irradiation,or UVA-preirradiated quinolone up to 100µM had no effect.indomethacin even at 0.1 µM completely inhibited the PGE₂elevation induced by 100 µM SPFX with UVA. These resultssuggest that PGs released from dermal fibroblasts in the simultaneouspresence of quinolone and UVA could contribute in part to thedevelopment of skin inflammation in vivo.     

Regulation of intracellular metabolism by biodegradable polyrotaxanes

Cellular response to our designed biodegradable polyrotaxanes was investigated in terms of changes in cytoplasmic calcium levels in platelets. The polyrotaxanes regulated thrombin-induced calcium increase in platelets although constituent molecules of the polyrotaxanes showed fewer effects on the intracellular metabolism. Further, an increase in membrane fluidity of red blood cell ghosts was significantly observed by the addition of the polyrotaxanes. Static light scattering study revealed that the polyrotaxanes formed a supramolecular association state in relation to the molecular weight of PEG: a loosely packed association with a specific molecular shape. From these characteristics, it is suggested that supramolecular level interactions between the polyrotaxanes and cell membranes regulate the intracellular metabolism. It is concluded that these biodegradable polyrotaxanes can be feasible as temporarily-controlled bioactivator.     

Laparoscopic cholecystectomy in the elderly: Analysis of pre-operative risk factors and postoperative complications

A retrospective study was conducted of two groups of patients over (group 1, n= 57) and under (group 2, n= 655) the age of 70 years who underwent laparoscopic cholecystectomy (LC). The pre-operative physical status and systemic complications, operation time, postoperative complications, postoperative hospital stay and other clinical features of the two groups were compared. The incidence of pre-operative complications in group 1 was significantly higher than that in group 2 (P < 0.05). Postoperatively no severe complication was found in any patient. Group 1 showed significantly prolonged operation time and postoperative hospital stay compared with group 2 (P < 0.05). The difference between the groups in the intra-operative treatment time and postoperative treatment is attributed to the greater prevalence of common bile duct stone in group 1 as there was little difference between the groups in the postoperative recovery after exclusion of these patients. No pulmonary complications, which are associated with LC, were observed; the postprocedure pain was slight and the period of bedrest was short. If complications associated with pneumoperitoneum can be prevented, this surgery is an excellent measure to improve the quality of life of even elderly patients with cholecystolithiasis.     

Prestretch potentiation of human skeletal muscle during ballistic movement

The conditions associated prior to and during the transition from prestretch to shortering may have considerable influence on the final performance of muscle. In the present study male subjects of good physical condition performed vertical jumps on the force-platform with and without preliminary counter movement. In the counter movement jump (CMJ) the amplitude of the knee bending, velocity of the prestretch and the force attained at end of prestretch were the primary parameters of interest. In addition the coupling time indicating the transition from the eccentric (prestretch) phase to the concentric phase was recorded from the angular displacement and reaction force curves. In the final calculation the mechanical performance parameters of CMJ were always compared with those of the jumps performed without counter movement. The results indicated in general first that CMJ enhanced the average concentric force and average mechanical power by 423 N (66%) and 1158 W (81%), respectively. This potentiation effect was the higher the higher was the force at end of prestretch (p<0.001). Similarly, the prestretch speed (p<0.001) and short coupling time (p<0.01) were associated with enhanced performance during the concentric phase. The average coupling time was 23 ms. The results are interpreted through changes in the prestretch conditions to modify the acto-myosin cross-bridge formation so that the storage and utilization of elastic energy is associated with high prestretch speed, high eccentric force and short coupling time. The role of the reflex potentiation is also suggested as additional enhancement of the final performance.     

Store and recoil of elastic energy in slow and fast types of human skeletal muscles

Stretch-shortening cycle refers to the mechanical condition in which store and recoil of elastic energy occur in the skeletal muscle. This leads to a greater work output when compared to a simple shortening contraction. The subjects performed vertical jumps with and without preliminary counter-movement and with small and large knee angular displacement. The results indicated that those subjects who had more fast twitch (FT) fibers benefited more from the stretching phase performed with high speed and short angular displacement. The amounts of elastic energy stored in this phase were 30 and 26 N × kgBW^-1, respectively, for FT and slow twitch (ST) type subjects. The recoil of elastic energy was proportional to the amount of energy storage. In large amplitude jumps where transient period between stretch and shortening is long the both types of subjects demonstrated similar amount of storage of elastic energy (17 and 16 N × kgBW^-1, respectively). However, the re-use of this elastic energy was greater in ST group (24%) as compared to the FT group (17%). The results can be interpreted through differences in sarcomere cross-bridge life times between fast and slow muscle fibers. The slow type muscle may be able to retain the cross-bridge attachment for a longer period of time and therefore it may utilize elastic energy better in a slow type ballistic motion.     

Influence of lactate accumulation of EMG frequency spectrum during repeated concentric contractions

One hundred and twenty consecutive maximal leg extensions at a constant angular velocity of 1.5 radians. s^-1 were performed by nine physical education students. Integrated electromyographic (IEMG) activity and power spectrum density function (PSDF) of the EMG were recorded from m. vastus lateralis, m. vastus medialis and m. rectus femoris using bipolar surface electrodes. Muscle biopsies were obtained from m. vastus lateralis before and after exercise. Tissue samples were analyzed for muscle fiber type distribution and lactate and glycogen concentration. Muscle force and IEMG decreased in parallel over the exercise period. Thus, the IEMG/force ratio was unchanged. Mean power frequency (MPF) of PSDF of the three muscles decreased by 10% (p<0.001) during the initial 25 contractions with no further decline during the latter part of exercise. The relative contribution of the highest bandwidth (130–500 Hz) of the PSDF decreased (p<0.001) between the first and final contractions. Muscle glycogen concentration decreased from 85 ± 23 to 68 ± 22 mmol ± kg^-1 w. w.during the exercise. Muscle and blood lactate concentration averaged 12.1 ± 8.8 mmol ± kg^-1 w. w.and 3.8 ± 0.8 mmol ± l^-1, respectively. The relative changes in MPF and in the highest bandwidth were correlated with muscle lactate concentration and fiber type distribution: in individuals with a high proportion of fast twitch muscle fibers and/or the greatest lactate accumulation, MPF and high frequency components of EMG PSDF decreased most markedly. Reductions in muscle force and IEMG are suggested to be partly due to a decreased motor neuron firing rate. It is discussed whether lactate or associated metabolic changes are influencing the motor unit action potential through feedback processes     

Predominant Production of Amniotic Interleukin-1α in Cases With Premature Rupture of the Membranes

PROBLEM: The physiological significances of the two known subtypes of interleukin-1 (IL-1) in amniotic fluid (AF) were examined by measurements of their concentrations and detection of their location. METHOD: Each IL-1 subtype in AF collected from 61 patients were examined by newly developed enzyme-linked immunosorbent assay with high sensitivity. Placenta and umbilical cord from 17 patients were examined immunohistochemically for localization of IL-1. RESULTS: Different types of IL-1 were predominant in AF; the mean (± SE) concentration of IL-1β (412.8 ± 105.4pg/ml) was significantly higher (P<0.01) than that of IL-1α(116.4± 26.7 pg/ml) in cases with spontaneous vaginal delivery, whereas the concentration of IL-1α (243.1 ±81.4pg/ml) was significantly higher(P<0.01)than that of IL-1β (139.7±59.4pg/ml) in cases with premature rupture of the membranes (PROM) without intrauterine infection. In these cases, immunohistochemical studies revealed the presence of IL-1α in the trophoblastic layer of the placenta and epithelium of the umbilical cord. CONCLUSIONS: Amniotic IL-1α was detected predominantly in cases with PROM, and it is thought to be produced in placenta and fetal skin keratinocyte.