Immediate pain relief effect of low level laser therapy for sports injuries: Randomized, double-blind placebo clinical trial.

OBJECTIVES: To determine the immediate pain relief effect of low-level laser therapy on sports injuries in athletes and degree of pain relief by the therapy. DESIGN: Double-blind, randomized, comparative clinical study. METHODS: Participants were 32 college athletes with motion pain at a defined site. Participants were randomized into two groups in which the tested or placebo laser therapy was administered to determine pain intensity from painful action before and after laser irradiation, using the Modified Numerical Rating Scale. The post-therapeutic Modified Numerical Rating Scale score was subtracted from the pre-therapeutic Modified Numerical Rating Scale score to determine pain intensity difference, and the rate of pain intensity difference to pre-therapeutic Modified Numerical Rating Scale was calculated as pain relief rate. RESULTS: Low-level laser therapy was effective in 75% of the laser group, whereas it was not effective in the placebo group, indicating a significant difference in favor of the laser group (p<0.001). Pain relief rate was significantly higher in the laser group than in the placebo group (36.94% vs. 8.20%, respectively, p<0.001), with the difference in pain relief rate being 28.74%. CONCLUSIONS: Low-level laser therapy provided an immediate pain relief effect, reducing pain by 28.74%. It was effective for pain relief in 75% of participants.

[Mitral valve replacement for cabergoline-related severe mitral regurgitation].

An 82-year-old man was referred to our hospital because of progressive heart failure. He had Parkinson's disease and had been treated with cabergoline during the preceding 4 years and 8 months. Echocardiography revealed severe mitral regurgitation through retracted mitral leaflets with incomplete coaptation. Heart failure persisted despite pharmacologic therapy, so the mitral valve was surgically replaced with a biological valve. Histologic analysis showed fibrous thickened mitral chordae with myxoid degeneration. These characteristics of the mitral valve of our patient are similar to the valvular heart disease described with the use of cabergoline. Clinicians must be care of valvular heart disease whenever they treat Parkinson's disease patients with cabergoline.

Regulation kinetics of Na+-Ca2+ exchange current in guinea-pig ventricular myocytes.

To investigate the regulation of native cardiac Na+-Ca2+ exchange by cytoplasmic Na+ (Na+i) and Ca2+ (Ca2+i), we recorded the Na+-Ca2+ exchange current (INa-Ca) from inside-out 'macro patches' excised from intact guinea-pig ventricular cells. The half-maximal concentration (Kh) of Ca2+i required to induce an inward INa-Ca was 7 µM. The Kh of Na+i required to induce an outward INa-Ca was 21 mM, and tended to decrease at the steady state of Na+-dependent inactivation. The time constant (tau) of Na+-dependent inactivation was ~1.5 s at 100 mM Na+i and 1 µM Ca2+i. The Kh for Na+i was 14 mM. Ca2+i augmented the peak outward INa-Ca (Kh = 0.2 µM) and attenuated Na+-dependent inactivation (Kh = 2.2 µM). The outward INa-Ca was activated by 5 µM Ca2+i with a half-time to reach steady state (t½) of ~0.4 s. This activation was composed of two exponential processes. Deactivation of the current upon Ca2+i removal also consisted of two exponential processes and had a t½ of ~0.5 s. A Na+-Ca2+ exchange model, consisting of one consecutive 4Na+:1Ca2+ exchange cycle and two inactive states, well mimicked the experimental data with regard to ion dependencies and regulation kinetics. These data provide detailed information on the kinetics of the Na+i- and Ca2+i-dependent regulation of native Na+-Ca2+ exchange. They also indicate that the regulation kinetics operate faster in macro patches than in the giant membrane patch from cardiac 'blebs', or in Xenopus oocytes expressing a cloned exchanger (NCX1.1).

Regulation kinetics of Na+-Ca2+ exchange current in guinea-pig ventricular myocytes.

To investigate the regulation of native cardiac Na+-Ca2+ exchange by cytoplasmic Na+ (Na+i) and Ca2+ (Ca2+i), we recorded the Na+-Ca2+ exchange current (INa-Ca) from inside-out 'macro patches' excised from intact guinea-pig ventricular cells. The half-maximal concentration (Kh) of Ca2+i required to induce an inward INa-Ca was 7 microM. The Kh of Na+i required to induce an outward INa-Ca was 21 mM, and tended to decrease at the steady state of Na+-dependent inactivation. The time constant (tau) of Na+-dependent inactivation was approximately 1.5 s at 100 mM Na+i and 1 microM Ca2+i. The Kh for Na+i was 14 mM. Ca2+i augmented the peak outward INa-Ca (Kh = 0. 2 microM) and attenuated Na+-dependent inactivation (Kh = 2.2 microM). The outward INa-Ca was activated by 5 microM Ca2+i with a half-time to reach steady state (t1/2) of approximately 0.4 s. This activation was composed of two exponential processes. Deactivation of the current upon Ca2+i removal also consisted of two exponential processes and had a t1/2 of approximately 0.5 s. A Na+-Ca2+ exchange model, consisting of one consecutive 4Na+:1Ca2+ exchange cycle and two inactive states, well mimicked the experimental data with regard to ion dependencies and regulation kinetics. These data provide detailed information on the kinetics of the Na+i- and Ca2+i-dependent regulation of native Na+-Ca2+ exchange. They also indicate that the regulation kinetics operate faster in macro patches than in the giant membrane patch from cardiac 'blebs', or in Xenopus oocytes expressing a cloned exchanger (NCX1.1).

Therapeutic efficacy of cefozopran in a murine model of haematogenous pneumococcal meningitis.

Antimicrobial regimens for the treatment of pneumococcal meningitis are not established. We have produced a murine model of haematogenous pneumococcal meningitis and have examined its usefulness for determining the required dosage and term of antimicrobial agents. Streptococcus pneumoniae serotype 6 was injected intraperitoneally (inoculum: about 1 x 10(4) CFU) into mice. Although half of the mice died within 2 days, the surviving mice showed positive bacterial cultures, increase of the protein level, decrease of the glucose level and infiltration of polymorphonuclear leucocytes into cerebrospinal fluids (CSF). When cefozopran was administered subcutaneously twice a day for 1-3 days starting 2 days after infection, dose- and duration-dependent effects were observed and all mice treated with 20 mg/kg of cefozopran for 3 days survived. The penetration rate of cefozopran from blood to CSF in infected mice was 44.7%, which was 6 times higher than that obtained in uninfected mice. This model may be useful for investigating the pathogenesis of haematogenous pneumococcal meningitis and its therapy.

Expression of Shaker-type voltage-gated potassium channel genes in the guinea-pig.

Few potassium channel genes have been isolated in the guinea-pig despite detailed electrophysiological characterization of potassium channels in the guinea-pig heart. We obtained partial clones of Shaker-type potassium channel genes in the guinea-pig and demonstrated their tissue distribution. Partial clones of the Shaker-type potassium channel genes were obtained by RT-PCR or genomic PCR. mRNA expression was measured by RNase protection assays in the heart, brain, and skeletal muscle. Three of the five obtained channel genes were expressed in the guinea-pig heart; Kv1.2, Kv1.3, and Kv1.6. Kv 1.6 expression was markedly at a higher level in the atrium than in the ventricle. Expression of the channel genes in the guinea-pig was different from that in human and rat, which may contribute to the species-specific action potential waveform.

Hematuria in patients with renal hypouricemia.

The characteristics of urate metabolism in renal hypouricemic patients with hematuria were studied to clarify the risk factors for hematuria in patients with renal hypouricemia. In 16 Japanese patients with isolated renal hypouricemia, urate metabolism was measured using the urate clearance study and the subtype of renal hypouricemia [defective presecretory reabsorption (Pre), defective postsecretory reabsorption (Post), enhanced tubular secretion (Secretion) and defective presecretory and postsecretory reabsorption (Pre&Post)] were determined by the pharmacological tests. Hematuria was seen in 7 out of the 16 patients (44%), all of whom were females (58%). Serum urate and urinary urate concentrations were significantly higher in the group with hematuria (Sur = 1.76 +/- 0.31 mg/dl and Uur/Ucr = 0.75 +/- 0.12: p<0.05) than in the group without hematuria (Sur = 1.44 +/- 0.46 mg/dl and Uur/Ucr = 0.56 +/- 0.04), although there was no difference in the urate excretion rate between the two groups. Hematuria was more likely to be accompanied by Post (75%) and Secretion (75%), which showed significantly higher urinary urate concentration (Uur/Ucr = 0.75 +/- 0.1 and 0.69 +/- 0.13, respectively) than by Pre (25%) and Pre&Post (0%), which showed lower urinary urate concentration (0.61 +/- 0.06 and 0.62 +/- 0.05, respectively). The risk factors for hematuria in patients with renal hypouricemia are the elevation of urinary urate concentration and the subtypes of Post and Secretion.

Influence of extracellular H+ and Ca2+ on Ro 22-9194-induced block of sodium current in cardiac myocytes.

1. Ro 22-9194 reduced the Na current in ventricular myocytes in either a tonic block or phasic block manner. 2. Ro 22-9194 had a higher affinity to the inactivated state (Kdi = 10.3 microM) than to the rested state (Kdrest = 180 microM). 3. Extracellular acidification enhanced the tonic block but reduced the phasic block. 4. Elevation of extracellular Ca2+ inhibited the enhancing effects of extracellular acidification. 5. These findings suggest that Ro 22-9194 strongly inhibits Na+ channels of the ventricular myocytes of the diseased hearts, characterized by the depolarized cell membranes and by acid conditions.

A novel mutation causing complete deficiency of thyroxine binding globulin.

OBJECTIVE: Thyroxine binding globulin (TBG) is a serum protein that transports thyroxine. Three naturally occurring mutations have been reported to produce complete deficiency of TBG (TBG-CD). The first to be reported was TBG-CD5 in caucasian families of French-Canadian origin and consists of substitutions in exons 2 and 3. TBG-CD of English ethnic origin (TBG-CD6) is characterized by a thymine deletion in codon 165 (exon 1). In Japanese families with TBG-CD (TBG-CDJ), a variant has been characterized with a deletion of the first base of the codon for amino acid 352 (exon 4) in the common type TBG. In this communication we report a new type of TBG-CD in a family of Japanese ethnic origin that is characterized by a single nucleotide substitution in place of two nucleotides in exon 1. This is an uncommon mutation which we have been unable to find in other genes. DESIGN: Exons of the TBG gene amplified by the polymerase chain reaction (PCR) were subcloned and sequenced. To examine for the presence of the same mutation in potentially affected individuals, we performed PCR using primer-directed mutagenesis or allele-specific amplification. PATIENTS: The index case was of Japanese ethnic origin, and was diagnosed as having TBG deficiency on the basis of undetectable serum TBG. The patient consented to this evaluation and the protocol was in accordance with IRB standards. MEASUREMENTS: Serum thyroid hormones, thyrotrophin binding inhibitory immunoglobulin and TBG concentrations were measured by conventional radio-immunoassay. Genomic DNA was extracted from white blood cells. RESULTS: In the index case exons 2, 3 and 4 were normal, but nucleotides 144 (cytosine) and 145 (thymine) in exon 1 were substituted with a single base (adenine) which induced a frame shift in the reading frame, resulting in an early stop codon at codon 51. The patient and his daughters were confirmed as having this mutation using primer-directed mutagenesis or allele-specific amplification. CONCLUSIONS: We have described a novel mutation in the TBG gene in a Japanese family. This results in a frame shift and premature stop codon, and was associated with undetectable serum TBG in the index case.

Tonic block of the Na+ current in single atrial and ventricular guinea-pig myocytes, by a new antiarrhythmic drug, Ro 22-9194.

Ro 22-9194 reduced the Na+ current in the atrial myocytes as well as ventricular myocytes in a tonic block fashion. Ro 22-9194 had a higher affinity to the inactivated state Na+ channels (KdI = 3.3 microM in atrial myocytes, KdI = 10.3 microM in ventricular myocytes) than to those in the rested state (KdR = 91 microM in atrial myocytes, KdR = 180 microM in ventricular myocytes), which indicated that Ro 22-9194 had a higher affinity to the Na+ channels in atrial myocytes than in ventricular myocytes. Ro 22-9194 shifted the inactivation curve in the hyperpolarized direction in both atrial and ventricular myocytes. These findings suggest that Ro 22-9194 more strongly inhibited the Na+ channel of the atrial myocytes of the diseased hearts with the depolarized membranes potentials than the Na+ channels in ventricular myocytes.

Streptococcus pneumoniae in the nasal cavity of mice causes lower respiratory tract infection after airway obstruction.

A model of persistent colonisation in the nasal cavity of mice by Streptococcus pneumoniae has been established. S. pneumoniae NNP-4 was introduced to the lungs of CBA/J mice at a density of c. 10(4) cfu/lung by an aerosol method and a high dose of ampicillin was administered 1 h after infection. This antibiotic eliminated bacteria from the lungs and trachea, but did not affect the bacterial counts in the nasal cavity. In mice given ampicillin, the bacteria were recovered from the nasal cavity only more than 2 weeks after infection, but IgG antibody against the colonising organisms was produced in sera around day 8 after infection. Airway obstruction was induced by intratracheal injection of formalin 2% into mice. Organisms appeared in the lungs in greater numbers when formalin was injected before the antibody production than when the immunity was established. In the early stages of infection, 10(3)-10(4) cfu appeared in the lungs 6 h after the formalin injection and the bacterial counts increased to c. 10(6) cfu within 24 h. When ampicillin was administered again 1 h after formalin was given, no bacteria were recovered from lungs 6 h later. However, in some of the mice given ampicillin after formalin, bacteria appeared in the lungs on the next day and the bacterial counts increased thereafter. These results suggest that S. pneumoniae in the nasal cavity invade the lower respiratory tract and that these organisms can localise and proliferate in lungs in the event of damage to the airway.

Optically active antifungal azoles. V. Synthesis and antifungal activity of stereoisomers of 3-azolyl-2-(substituted phenyl)-1-(1H-1,2,4-triazol-1-yl)-2- butanols.

The (2S,3S)-, (2R,3S)- and (2S,3R)-stereoisomers of (2R,3R)-3-azolyl-2-(substituted phenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanols [(2R,3R)-1a--d] were prepared and evaluated for antifungal activity against Candida albicans in vitro and in vivo to clarify the relationships between stereochemistry and biological activities. The results revealed that the in vitro antifungal activity in each set of the four stereoisomers [(2R,3R)-, (2S,3S)-, (2R,3S)- and (2S,3R)-1a--d] definitely paralleled the in vivo antifungal activity against candidosis in mice, and the order of potency was (2R,3R) >> (2R,3S) > or = (2S,3S) > or = (2S,3R). In addition, the four stereoisomers in each set were assessed for sterol biosynthesis-inhibitory activities in C. albicans and rat liver. The (2R,3R)-isomer was found to exert a strong and selective inhibitory effect on the sterol synthesis in C. albicans as compared with that in rat liver.