ACETALDEHYDE METABOLISM: DIFFERENCES BETWEEN UChA AND UChB RATS

In order to explore the influence of acetaldehyde (AcH) metabolismon the voluntary ethanol intake of genetically low (UChA) andhigh (UChB) ethanol consumer rats, the AcH disappearance rate(ADR) after incubation with homogenates and subcellular fractionsfrom liver and brain was determined. In addition, the effectof disulfiram pretreatment on AcH metabolism was studied. Maleadult rats of both strains were used. ADR was assayed in totalhomogenates, and in mitochondrial as well as 9000 g supernatantfractions of liver and brain. AcH was measured by gas chromatography.In some experiments, rats were pretreated with disulfiram (300mg/kg po) 24 hr before the studies. The result showed no straindifference in ADR in homogenates or subcellular fractions ofliver from untreated rats, but for disulfiram pretreated ratsa significantly lower decrease of ADR in samples from UChB comparedto UChA rats was observed. This result is consistent with alower peak AcH level in UChB compared to UChA rats after a loadof ethanol (60 mmole/kg ip). Concerning brain homogenates, ahigher ADR was observed in homogenates and crude mitochondrialfractions of UChB than of UChA rats. This difference was notobserved when the incubation was performed without adding NADor in the absence of oxygen. These results provide evidenceof strain differences in mitochondrial AcH metabolism, the natureand origin of which deserve further study.     

The cold pressor test: Vascular and myocardial response patterns and their stability

The purposes of the present study were to compare the cardiovascular response patterns evoked by three versions of the cold pressor test (either forehead stimulation or hand or foot immersion) and to determine the reproducibility of the responses over a 2-week interval. Blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance, and systolic time intervals were obtained during rest and during the cold pressor test in 42 young men. Across conditions, the pressor response was supported by peripheral resistance increases with concomitant stroke volume decreases. Although the response panerns were generally similar across sites, exceptions were apparent for heart rate. Forehead stimulation was characterized by no significant change in heart rate, whereas limb (hand or foot) immersion was associated with significant heart rate acceleration. The responses elicited by the three cold pressor test conditions were reliable and showed little evidence of attenuation over the test-retest interval.     

Smooth muscle myosin light chain kinase is transiently expressed in skeletal muscle during embryogenesis and muscle regeneration both in vivo and in vitro

Byusing a polyclonal antibody raised against smooth muscle MyosinLight Chain Kinase of adult chicken we show that the 135 kDasmooth muscle Myosin Light Chain Kinase isoform is present inneonatal and regenerating rat skeletal muscle, as well as inadult atrial myocardium. No reaction was evident in adultskeletal muscle fibres. In neonatal and in early regeneratingmuscle smooth muscle Myosin Light Chain Kinase is associated withembryonic myosin as revealed by their co-presence in musclefibres. Experiments in vitro show the same results in myotubes.In atrial myocardium there is a patchy positivity in certaingroup of myocytes. Immunoblotting experiments show in muscle cellcultures, in neonatal and in regenerating skeletal muscle aprotein band with electrophoretic mobility corresponding to thatof smooth muscle Myosin Light Chain Kinase. These results suggestthat the expression of smooth muscle Myosin Light Chain Kinase isnot fully tissue-specific and that regulation of the contractilemachinery could be different during myogenesis and in adulthood,in relation to the peculiar dynamic characteristics of developingmuscles     

ANIMAL MODELS FOR OSTEOARTHRITIS--ENSURING EXPERIMENTAL VALIDITY

Confounding factors, bias factors and hidden variables affectthe design of experiments involving animal models. In a frequentlyused dog model for osteoarthritis these can arise, for example,because of the influence of age, sex and breed of dog. Controlsare required to investigate the progression of osteoarthritiseven in experiments forming time series. However, there areno true controls in animal models for joint degeneration. Analysisof data collected from experiments involving animal models dependson the number of factors being varied. The number of animalsinfluences the level of confidence associated with a result.Ignoring statistics can invalidate conclusions drawn from theexperiments. Statistical considerations are also important inthe presentation of results KEY WORDS: Joint degeneration, Dogs, Controls, Study design     

Effects of Cimetidine on Sinus Node Function and Atrioventricular Conduction in Man

Electrophysiological effects of H2-receptor blockade 200 mg cimetidine IV on sinus node (SN) function and atrioventricular (AV) conduction were evaluated. Tests were performed in 21 people in basal state (group I), and in 14 people (group II) after autonomic blockade (AB) (propranolol 0.2 mg/kg, and atropine 0.04 mg/kg). We analyzed sinus cycle length (SCL), sinus node recovery time (SNRT), corrected sinus node recovery time (CSNRT), and secondary pause (SP) as the longest sinus pause after incremental overdrive pacing, sinoatrial conduction time (Strauss method) (SACT), Wenckebach point (WP), and blood pressure (BP). In group I, cimetidine prolonged SCL (717 ± 98 vs 860 ± 138 msec P < 0.001), SNRT (1161 ± 153 vs 1263 ± 163 msec P < 0.002), SP (943 ± 183 vs 1072 ± 187 msec P < 0.001), SACT (121 ± 20 msec vs 149 ± 21 msec P < 0.002), and lowered rate at which AV nodal Wenckebach point were observed (169 ± 24 vs 160 ± 26 beats/min P < 0.02). The drug did not produce significant change of the CSNRT (439 ± 121 vs 402 ± 107 msec. In group II, after AB cimetidine prolonged SCL (643 ± 79 vs 656 ± 86 msec P < 0.05), SP (686 ± 114 vs 717 ± 109 msec P < 0.05) and lowered WP (170 ± 19 vs 166 ± 19 beats/min P < 0.02) significantly. The effects of cimetidine, after AB on SNRT (894 ± 180 vs 920 ± 164 msec, CSNRT (243 ± 99 vs 255 ± 85 msec), SACT (85 ± 20 msec vs 90 ± 22 msec) were not significant. We conclude that H2-receptor blockade decreases SN automatically, prolongs SACT and AV conduction in man. The study suggests that histamine takes part in regulation of electrophysiological properties of the human heart in vivo.     

ITRACONAZOLE VERSUS GRISEOFULVIN IN THE TREATMENT OF TINEA CAPITIS: A DOUBLE-BLIND RANDOMIZED STUDY IN CHILDREN

Background. Tinea capitis is a fungal infection in which topical therapy is often unsuccessful. Griseofulvin has been considered to be a first-line therapy. Other antifungal agents are the azole derivatives. Among these, itraconazole was compared with griseofulvin in children in a double-blind study. Patients and Methods. Thirty-four children and one adult with clinical signs and symptoms of tinea capitis and with positive culture and microscopy for dermatophytes have been included in a double-blind comparison between itraconazole, 100 mg daily, and ultramicronized griseofulvin, 500 mg daily. Both drugs were given for 6 consecutive weeks. The final evaluation was made 8 weeks after the end of treatment to allow the hairs to regrow. Seventeen itraconazole- and 15 griseofulvin-treated patients received the complete 6-week treatment course. Fifteen of these 17 itraconazole patients and 14 of the 15 griseofulvin patients had infections caused by Microsporum canis. Fifteen of 17 patients were cured by itraconazole (88%) and 15 of 17 patients by griseofulvin (88%). One of the patients who discontinued griseofulvin therapy after 4 weeks was clinically and mycologically cured. Two of the original 17 griseofulvin patients discontinued therapy because of vomiting. None of the itraconazole-treated children experienced side effects. Conclusions. Itraconazole is the first azole derivate that matches griseofulvin for the treatment of tinea capitis in children. The drug also appears to be better tolerated than griseofulvin.