Chemotaxis of polymorphonuclear leukocytes towards human pre-ovulatory follicular fluid and serum using a 'sparse-pore' polycarbonate filtration membrane.

The chemotactic responses of polymorphonuclear leukocytes (PMN) towards pre-ovulatory follicular fluid and serum from patients participating in an in vitro fertilization program were tested in a modified Boyden chamber using a 'sparse-pore' polycarbonate filtration membrane method. The chemotactic activities of follicular fluids were generally low, but were significantly higher in conceptual cycles than in non-conceptual cycles. The chemotactic activities of sera were generally high, but were significantly lower in conceptual cycles. The chemotactic activity of few follicular fluids ever exceeded that of serum, regardless of the occurrence of conception. These findings demonstrate for the first time using an appropriate technique, that pre-ovulatory follicular fluids can be chemotactic for PMN, but the relationship between this activity, serum chemotactic activity and successful pregnancy is not clear.

The role of therapeutic drug monitoring in the care of epileptic patients.

Plasma concentrations of anti-epileptic drugs were measured in outpatients with a positive diagnosis of idiopathic epilepsy. Dosage adjustments were based on pharmacokinetic principles to obtain optimal seizure control and drug utilization. By means of the sign test the decrease in the frequency of seizures was shown to be statistically significant (P = 0,00024), as was the decrease in the number of anti-epileptic drugs being used concurrently (P = 0,00098). Combined with judicious clinical observation, measurement of blood levels of antiepileptic drugs can contribute greatly to the successful management of the epileptic patient.

Creatinine excretion as an index of myofibrillar protein mass in dystrophic mice.

1. Daily creatinine excretion in the urine of normal and dystrophic mice was determined and then the carcass proteins were quantitatively extracted into soluble, myofibrillar and collagenous fractions. 2. On a live body-weight basis, total carcass protein was 15% lower in dystrophic than in normal mice. Relative to carcass weight, however, the amount of protein was significantly lower only in male dystrophic mice. 3. The myofibrillar protein fraction comprised 36 . 3 and 32 . 5% of the total protein in male and female dystrophic mice and 48 . 8 and 45 . 0% respectively in normal mice. The decrease in myofibrillar protein in dystrophic mice was accompanied by an increase in the residual collagenous fraction of proteins. 4. The rate of excretion of creatinine was strongly correlated (r = +0 . 98) with the myofibrillar protein mass in each mouse. This relationship was the same for both normal and dystrophic mice, each gram of myofibrillar protein being associated with 3 . 6 mumol of creatinine excreted/day. 5. The creatinine excretion rate is a valid index of contractile muscle mass in murine dystrophy.

Increased rates of myofibrillar protein breakdown in muscle-wasting diseases.

The excretion of endogenous creatinine and 3-methylhistidine by subjects with muscle diseases has been measured in order to assess muscle mass and fractional rates of myofibrillar protein degradation. Increases in the rates of myofibrillar protein breakdown were observed in all subjects with Duchenne, Becker, autosomal recessive Duchenne-like, and limb-girdle muscular dystrophy; dystrophia myotonica; myotonia congenita; peroneal muscular atrophy; myasthenia gravis; and central core disease; in some cases of spinal muscular atrophy; but in no cases of facioscapulohumeral muscular dystrophy of dystonia musculorum deformans. All increases in myofibrillar protein breakdown were associated with reductions in muscle proportion below the normal. Muscle-wasting diseases may respond to therapy directed towards an inhibition of muscle protease activity; the efficacy of such therapy can be monitored by the 3-methylhistidine-to-creatinine excretion ratio.

Metabolism of glucose, fructose and lactate in vivo in chronically cannulated foetuses and in suckling lambs.

1. Chronically cannulated sheep foetuses and suckling lambs were injected with 14C-labelled glucose, fructose or lactate, and sequential blood samples taken under conditions of minimal stress and without anaesthesia. 2. Gluconeogenesis from lactate was not detectable in foetal sheep, but the pathway was active in suckling lambs. 3. Fructose utilization rates were low in foetal sheep, with no measurable conversion into glucose or lactate. 4. The high rates of irreversible loss of both glucose and lactate in the foetus were decreased in suckling lambs. Radioactivity from labelled glucose entered both the lactate and fructose pools in foetal sheep, and entered the lactate pool in suckling lambs. 5. A model is proposed in which carbon flow between glucose, fructose and lactate has been quantified in foetal sheep.

The appearance of gluconeogenesis at birth in sheep. Activation of the pathway associated with blood oxygenation.

1. Measurements of pyruvate carboxylase, mitochondrial phosphoenolpyruvate carboxykinase (GTP), hexose bisphosphatase and glucose 6-phosphatase in developing sheep liver showed substantial activities of all enzymes in the foetus, especially towards the end of gestation. Cytosol phosphoenolpyruvate carboxykinase (GTP) in livers of mid-term foetuses was only 10% of the activity at birth. 2. All enzymes except pyruvate carboxylase showed 1.5-2-fold increases after birth. 3. Gluconeogenesis form [14C]actate could not be detected in chronically cannulated sheep foetuses at any developmental stage and was not initiated by the infusion of adrenaline or glucagon. 4. An active pathway of gluconeogenesis was evident in vivo within 2 min after natural birth or within 4 min after Caesarian delivery of term lambs, and was delayed in prematurely delivered lambs until breathing was established and the blood fully oxygenated. 5. It is proposed that oxygen availability initiates gluconeogenesis in the newborn lamb.