Effects of terbutaline on force and intracellular calcium in slow-twitch skeletal muscle fibres of the rat.

1. The effect of the alpha2-adrenoceptor agonist, terbutaline, was investigated on simultaneously measured force and intracellular free calcium ([Ca2+]i) in intact rat soleus muscle fibres, and on contractile protein function and Ca2+ content of the sarcoplasmic reticulum (SR) in skinned fibres. 2. Terbutaline (10 microM) had no significant effect on either resting force or [Ca2+]i. Exposure to terbutaline increased both the integral of the indo-1 ratio transient and peak twitch force by 37%. 3. At sub-maximal (10 Hz) stimulation frequencies, terbutaline accelerated force relaxation but had highly variable effects on tetanic force amplitude. The corresponding indo-1 ratio transients were significantly larger, and faster to decay than the controls. 4. Terbutaline increased tetanic force at near maximal stimulation frequencies (50 Hz) by increasing tetanic [Ca2+]i. Force relaxation was accelerated at this frequency with no significant change in the indo-1 ratio transient decay rate. 5. All of terbutaline's effects on force and indo-1 ratio transients in intact fibres were completely blocked and reversed by ICI 118551 (1 microM). 6. Mechanically skinned fibres isolated from intact muscles pre-treated with terbutaline showed no significant changes in SR Ca2+ content, myofilament [Ca2+]i-sensitivity or maximum force generating capacity. 7. The results suggest that terbutaline primarily modulates force by altering the amplitude and decay rate of the [Ca2+]i transient via phosphorylation of both the ryanodine receptor (RR) and the SR pump regulatory protein, phospholamban (PLB). The high variability of responses of slow-twitch muscles to beta2-agonists probably reflects individual differences in basal phosphorylation levels of PLB relative to that of RR.     

AZATHIOPRINE INDUCED BONE MARROW SUPPRESSION IN LIVE RELATED RENAL ALLOGRAFT RECIPIENTS

Over a follow-up period of 6 years, 4 out of 31 live related renal allograft recipients (12.9%) developed azathioprine induced bone marrow suppression. Presentation in 3 patients was with fever and 2 patients also had associated graft dysfunction. All patients had leucopenia, 2 patients in addition had anaemia and one patient had pancytopenia. Bone marrow suppression developed 9.6 months (3.5-16.0 months) following transplantation and recovery followed over a period of 30 (18-49 days) days after withdrawal of the drug. One patient succumbed during the phase of bicytopenia.KEY WORDS: Azathioprine, Bone marrow suppression, Kidney transplantation     

CLINICO-PATHOLOGICAL CORRELATION IN NEONATAL AUTOPSIES

Of the 253 neonates admitted to a neonate intensive care unit during the period Jan 91 to Sep 93, 43 neonates died. Autopsy was done in 23 of these (53%). The mean duration of stay of the neonates in the intensive care unit prior to death was 5.6 days (range 2 hours to 10 days). Antemortem diagnoses included asphyxia neonatorum (4), meconium aspiration syndrome (2), septicemia (5), prematurity (3), birth trauma (2), congenital anomalies (2), hypoxic ischemic encephalopathy (1), and non-specific diagnosis (4). There were 6 major autopsy findings that, if known prior to death, would have altered clinical management and might have resulted in cure or prolonged survival. There were 8 additional major findings that, if known prior to death, would not have altered management There were 14 minor findings related to major diagnoses but unrelated to the primary cause of death.KEY WORDS: Autopsy, Cause of death, Perinatal mortality     

Verapamil in the prophylaxis of bronchial asthma

Summary A single oral dose of verapamil 80 mg was shown significantly to inhibit histamine-induced bronchoconstriction in 8 out of 16 asthmatic subjects (maximum increase in PD_20FEVHi 416%). There was still significant protection ( PD_20FEV1Hi>100%) in the responders 5 h after the oral dose. The relationship of the bronchoprotective effect to the plasma level of verapamil was also examined. Responders and non-responders did not differ significantly in the peak plasma level or the time course of the plasma verapamil concentration.The protective effect was not correlated with the peak plasma level of verapamil or with the baseline bronchial hyperreactivity.     

Antibiotic sensitivity of enteric pathogens in Vietnam

The in vitro antimicrobial susceptibilities of 675 common enteropathogenic isolates from faecal specimens of patients with diarrhea (E. coli, Shigella, Salmonella and V. cholerae), and 568 E. coli isolates from faecal flora of healthy persons, which were collected as part of a National antibiotic resistance surveillance in Vietnam, were determined. The agar dilution method was used for the following nine antibiotics: ampicillin, doxycycline, chloramphenicol, gentamicin, nalidixic acid, kanamycin, trimethoprim, trimethoprim in combination with sulfamethoxazole (1/20), and sulfisomidin. Gentamicin was the most active of the antibiotics tested against all bacterial species with MICs in the range 0.125-4 mg/l. All strains were susceptible to nalidixic acid (0.125-8 mg/l) and more than 90% were susceptible to kanamycin. Among E. coli and Shigella isolates from patients the frequencies of resistance to commonly used antibiotics were high: ampicillin 73% and 84%, doxycycline 83% and 94%, chloramphenicol 71% and 91%, sulfisomidin 82% and 92%, respectively. Resistance to trimethoprin, as well as to the combination with sulfamethoxazole was found in 21% and 23%, respectively. The frequencies of multiple resistance (resistance to three or more antibiotics) were also high (77% and 89%, respectively). Less than 10% of Salmonellae and V. cholerae isolates were resistant to ampicillin, sulfisomidin or trimethoprim. Among E. coli from healthy people the frequencies of resistance were lower than in isolates from patients: ampicillin 23%, doxycycline 40%, chloramphenicol 21% and sulfisomidin 34%. However, the same patterns of multiple resistance were found in both groups.     

兴山五味子的质量研究

兴山五味子;;襄五脂素;;主要药理作用     

Lung involvement in Langerhans' cell histiocytosis: prevalence, clinical features, and outcome.

In Langerhans' cell histiocytosis, the prognostic significance of pulmonary disease is controversial. The clinical and radiological features and lung function tests of Langerhans' cell histiocytosis patients presenting to a single tertiary referral center between 1981 and 1987 were reviewed. Age at diagnosis ranged from 2 weeks to 16 years (median 1.7 years) and the male-female ratio was 2.4:1. No child presented with lung involvement alone. In 18 (40%) of 45 patients with multisystem disease there was clinical and/or radiological evidence of lung pathology. Another 6 children (13%) with normal chest roentgenograms had abnormal lung function tests, suggesting subclinical ("occult") involvement. Those with overt lung disease tended to present at a younger than average age (median 0.6 years). The most common functional disturbance was reduced lung or respiratory compliance with reduced lung volumes. Patients with and without lung involvement showed a similar pattern of involvement of other organs, with skin and bone most commonly affected. Of the 45 children with multisystem disease, 38 (84%) survived 2 to 7 years after diagnosis; there was a similar proportion of deaths in children with and without lung involvement. It is concluded that lung involvement occurs in nearly half of young children with multisystem Langerhans' cell histiocytosis but does not adversely affect outcome.     

Use of mid-arm and head circumference to estimate gestational age and nutritional status of newborns]

1110 neonates, from 30 to 42 of estimated gestational age (EGA) were measured on the 1st day of life to estimate upper mid-arm circumference (MAC) and head circumference (HC). Individual MAC/HC ratio was calculated. MAC/HC ratio was used to estimate gestational age and nutritional status of the newborns. We proved that MAC/HC ratio increased linearly between 30 and 38 week of pregnancy and it stabilized between 38-42 week. We compared MAC/HC ratio with birth weight, skin fold score, and ponderal index. We concluded that this ratio may be very useful to estimate gestational age and to include the neonates to "the group of risk".     

Poly(ADP-ribose) polymerase-1 in the nervous system

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme, activated by DNA strand breaks to participate in DNA repair. Overactivation of PARP by cellular insults depletes its substrate NAD(+) and then ATP, leading to a major energy deficit and cell death. This mechanism appears to be prominent in vascular stroke and other neurodegenerative processes in which PARP gene deletion and PARP-inhibiting drugs provide major protection. Cell death associated with PARP-1 overactivation appears to be predominantly necrotic while apoptosis is associated with PARP-1 cleavage, which may conserve energy needed for the apoptotic process. Novel forms of PARP derived from distinct genes and lacking classic DNA-binding domains may have nonnuclear functions, perhaps linked to cellular energy dynamics.