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J L Bennett

Publications and source records attributed to J L Bennett.

At least 127 records · Page 7Linked to original sources
PubMed1982

Microelectrode studies of the tegument and sub-tegumental compartments of male Schistosoma mansoni: anatomical location of sources of electrical potentials.

Histological studies using horse-radish peroxidase (HRP) as a marker, injected iontophoretically through a recording electrode, have indicated the origins of potentials encountered upon advancement of the electrode into and beneath the dorsal surface of adult male Schistosoma mansoni. The first potential encountered, having a value of -51 +/- 0.6 mV originates across the outer tegumental membrane. The next potential has a value of -28 +/- 0.6 mV and originates in the muscle masses underlying the tegument. Finally, a potential having the value -10 +/- 0.5 mV originates within the basal lamina and the interstitial fibers and extracellular space surrounding the muscle. Altering ion concentrations in the bathing medium (i.e. high K+, low Na+, zero Ca2+, low Cl-, high Li+) depolarizes all three potentials. External applications of ouabain and the antischistosomal, praziquantel, also cause depolarization of the potentials. It appears that the muscle potential and the tegumental potential are primarily K+-dependent. The depolarizing effects of ouabain. LiCl and low Na+ suggest that active transport is important in the maintenance of the muscle potential, just as is the case for the tegumental potential. There appears to be a close correlation between changes in the tegumental, muscle and extracellular space potentials. The correlation between tegument and muscle potential changes might be explained by junctional complexes between tegumental cell bodies and muscle cell bodies.

Animals↗
PubMed1982

Microelectrode studies of the tegument and sub-tegumental compartments of male Schistosoma mansoni: an analysis of electrophysiological properties.

Standard intracellular microelectrode techniques were used to determine the electrical properties of the tegument and sub-tegumental regions in male Schistosoma mansoni. Three distinct compartments of electrical potential were observed. The resting potentials recovered in these compartments of -45.9 +/- 2.5 mV (Eteg), -22.0 +/- 1.1 mV (E2) and -4.7 +/- 03 mV (E3) corroborate those previously reported by Fetterer, Pax & Bennett (1980) and Bricker, Pax & Bennett (1981). Input resistance was measured in each compartment and was found to be 4. 5 M omega (tegument), 9.2 M omega (E2) and 3.5 M omega (E3). Time-constants for the tegument, E2 and E3 were 0.24 +/- 0.01 msec, 0.25 +/- 0.01 msec and 0.13 +/- 0.01 msec, respectively. Multiple electrode experiments revealed that the tegument and E2 compartment are electrical syncytia with similar current-spreading capabilities. Low resistance pathways also appear to connect the tegument and E2 region, since electrotonic signals initiated in either of those compartments experience only a 15-25% reduction upon passing into the other. Injecting large (greater than 200 nA) depolarizing current pulses into the tegument or E2 compartment often resulted in the initiation of active membrane responses. These spikes were highly variable, ranging from 4 to 75 mV in magnitude (occasionally overshooting zero potential by as much as 25 mV) and from 10-40 msec in duration. The responses were not actively propagated along the parasite, and their decay over distance was approximately equal to that predicted on the basis of length constant values obtained from electronic signals. The addition of a non-diffusible solute to the recording medium resulted in a significant reduction in the current-spreading capacity of both the tegument and E2 compartment. Coupling ratios between the tegument and E2 compartment. Coupling ratios between the tegument and E2 compartment were decreased, and the input resistance for both compartments increased, while resting potentials remained constant. Active responses could not be evoked in schistosomes exposed to the hyperosmotic medium.

Animals↗
PubMed1982

Oltipraz--antischistosomal efficacy in Sudanese infected with Schistosoma mansoni.

Oltipraz was administered orally to 62 hospitalized male Sudanese infected with Schistosoma mansoni. The patients were split into two equal groups; one group received a total dose of 25 mg/kg body weight, the other group received 35 mg/kg. Half of the total dose was given with breakfast, the second half with supper. In general, the drug was well tolerated although some vomiting was observed 3--5 hours after the second half-dose. Blood chemistry and hematology remained normal 24 hours after administration of oltipraz. The cure rate was above 95% for both groups at 1, 3, and 6 months after treatment. Stratification of patients by eggs/g feces clearly indicated that the drug was equally efficacious for patients excreting high, medium or low numbers of eggs. Our results indicate that further trials will be necessary with lower doses of oltipraz in order to determine its antischistosomal potency.

Administration, Oral↗
PubMed1982

Plasma spectrometric analysis for Na, K, Ca, Mg, Fe, and Cu in Schistosoma mansoni and S. japonicum.

The concentration of K, Na, Ca, Mg, Fe, and Cu in adult Schistosoma mansoni and S. japonicum was determined using plasma spectrometric analysis. There was no difference in elemental composition of Schistosoma mansoni pairs that were incubated in various media such as RPMI/1640, Eagle's medium or Hanks' balanced salt solution. These values were also equivalent to those obtained from worms directly extracted with 2% HCl. Female worms of both species contained a relatively higher concentration of Fe and Cu than the males. Incubation of worms at low temperature (0 C) but not at 37 C because an increase in Na and decrease in K compared to those at room temperature (21 C). Similar changes in Na and K values were also caused by treatment of worms with ouabain (10(-5) M) and also by incubation in Ca-free medium containing EGTA. Praziquantel (10(-6) M) caused a slight increase in Na content.

Animals↗
PubMed1982

Surface electrical activity from Schistosoma mansoni: a sensitive measure of drug action.

Spontaneous electrical activity was recorded by means of suction electrodes placed on the surface of adult, male Schistosoma mansoni. This electrical activity was a complex of bi- and triphasic potentials that ranged from smaller amplitude waves (0-40 microV) of high frequency (10-40/sec), to randomly occurring, larger amplitude waves (40-1,000+ microV) of lower frequency (0-5/sec). Many of the larger potentials (greater than 100 microV) appeared to be propagated. This activity varied with respect to the region of the parasite. The caudal region consistently exhibited potentials greater than 120 microV, whereas activity in the anterior region was rarely greater than 40 microV. Decreased concentrations of Ca++ (0.0 or 0.14 mM), an increased concentration of Mg++ (30.0 mM) or addition of a mM CoCl2 significantly decreased the level of electrical activity. Drug concentrations of 1 x 10(8) M carbachol, 1 x 10(-6) M metrifonate, 1 x 10(-8) dopamine, and 1 x 10(-5) M pentobarbital also significantly decreased electrical activity. In contrast, serotonin (1 x 10(-7) M) significantly increased the level of electrical activity.

Animals↗
PubMed1982

Effect of Triton X-100 on tegument and muscle in Schistosoma mansoni.

Short periods of in vitro incubation of Schistosoma mansoni with low concentrations of the nonionic detergent Triton X-100 caused marked changes in the physiological and morphological status of the parasite. Less than 15 min of exposure to 1 mM Triton at 37 C led to irreversible destruction of the tegument, relaxation and depolarization of the muscle, and loss of response to electrical stimulation, to 60 mM K+-HBS, or to 10(-6) M praziquantel. A 5-min incubation in 100 microM Triton X-100 caused no gross structural damage, changes in tegumental or E2 electrical potential, or decrease in response to praziquantel, but markedly inhibited the ability of 60 mM K+-HBS or electrical stimulation to cause muscle contraction. Radioactive calcium influx measurements indicated that a 5-min exposure to 100 microM Triton X-100 may be uncoupling membrane depolarization from development of muscle tension by interfering pharmacologically with calcium channels. Longer incubations (15 min) in the presence of 100 microM Triton X-100 caused transitional physiological changes suggesting that the mode of action of the detergent was passing from a specific, pharmacological mode to a nonspecific disruptive action.

Animals↗
PubMed1981

Na+-K+ transport, motility and tegumental membrane potential in adult male Schistosoma mansoni.

Ouabain applied to adult male Schistosoma mansoni causes a large, non-reversible tension increase of the parasite's musculature and elimination of spontaneous contractions. The tension increase and the time-course of tension development caused by ouabain are dose dependent with significant effects obtained at 3 x 10(-6) M. Digoxin and digoxigenin act in a similar manner with a relative potency of ouabain approximately or equal to digoxin greater than digoxigenin. Lowered temperature as well as substitution of Li+ for Na+ increases muscle tension. The membrane potential recorded from the ventral tegument is also affected by treatments which interact with Na+-K+ transport systems. Ouabain (0.1 mM) causes a rapid depolarization without a significant effect on membrane resistance. The tegument is depolarized by temperature below 30 degrees C. The effect of temperature is readily reversible and the temperature sensitivity is eliminated by pretreatment with ouabain. Substitution of Li+ for Na+ also causes a depolarization of the tegument. Tracer experiments show both an increase in Na+ and a decrease in K+ in the parasite within 10 min after treatment with ouabain (1 x 10(-5) M). Decreasing temperature of the bathing medium also causes an accumulation of Na+ as well as a K+ decrease in the animals. The above results indicate a significant role for active Na+-K+ transport in muscle contraction and in maintenance of the tegumental membrane potential. The data also suggest that the Na+-K+ transport in S. mansoni may be electrogenic.

Animals↗
PubMed1980

Praziquantel, potassium and 2,4-dinitrophenol: analysis of their action on the musculature of Schistosoma mansoni.

Praziquantel (PZ) (10(-6) M), an antischistosomal drug, 60 mM K+ and 2,4-dinitrophenol (DNP) induce a rapid contracture of the musculature in adult male S. mansoni. This event is accompanied, except for DNP, by an increased accumulation of 45Ca2+ in the parasite. K+-induced contractures had phasic and tonic components while DNP and PZ produced only tonic contracture of the parasites musculature. The Ca2+ antagonist, D-600 (10(-4) M) as well as La3+ (10 mM) and Co2+ (10 mM) prevented the 45Ca2+ accumulation produced by high K+. La3+ and Co2+ blocked the tension increasing effects of high K+; D-600 blocked only the tonic contractures. D-600 and Co2+ did not prevent the 45Ca2+ increase produced by PZ but La3+ did. D-600 did not block the PZ response but Co2+ and La3+ partially attenuated it. La3+ also partially attenuated the DNP response. Co2+ and D-600 prevented sustained contractures in response to DNP. Thus, although K+, PZ and DNP have the same final effect on the musculature of S. mansoni, it appears that their effects are not mediated by the same mechanisms.

2,4-Dinitrophenol↗
PubMed1980

Characteristics of antischistosomal benzodiazepine binding sites in Schistosoma mansoni.

The benzodiazepines, clonazepam and Ro 11-3128, have been identified as antischistosomal drugs (Stohler, 1978). Using [14C] Ro 11-3128 or [3H] clonazepam, we were able to demonstrate that male S. mansoni can specifically bind these labeled drugs. The binding sites on this parasite displayed characteristics of saturability and low affinity. The affinity of various benzodiazepines for the binding site on intact schistosomes correlated with their antischistosomal efficacy. Binding was markedly altered by agents known to destroy membrane integrity. Combined with previous studies (Pax et al., 1978), this work suggests that a specific, benzodiazepine binding site may be located on the epidermis of male S. mansoni.

Animals↗
PubMed1979

The effects of chronic disulfiram treatment on mice infected with Schistosoma mansoni.

Compounds which block the formation of the egg shell in female schistosomes are thought to have chemotherapeutic value. One of these compounds, disulfiram, when given chronically in the diet produced a 60% reduction in the mortality of mice carrying a heavy schistosome burden. This reduction in mortality was associated with an 80% decrease in granuloma formation. On the other hand, there was no decrease in the amount of periportal inflammation in drug-treated animals. While the use of this drug results in significant amelioration of schistosomal pathology, its effects are rapidly reversible, thus severely limiting its chemotherapeutic potential.

Animals↗