Restoration of voltage-dependent antibrain antibody-inhibited calcium current by cyclic adenosine monophosphate

A dual-microelectrode voltage clamp technique was used for recording voltage-dependent calcium current (I_ca) in unidentified neurons isolated fromHelix pomatia. Neither intracellular injection of cyclic adenosine monophosphate (cAMP; 10 nA, 5 min) nor intracellular application of dibutyril-cAMP (dcAMP; 1 mM, 10–20 min) induced a change in normal I_ca or produce a reversible 10–20% reduction in amplitude. Adding S-100 protein fraction antibodies to the external medium led to the onset of calcium-dependent inactivation of I_ca, bringing amplitude of I_ca down to 15±12% of its initial level. Either cAMP or dcAMP then restored inhibited I_ca to 50±11% of its original level. It was found that the effects of cAMP on I_ca of intact neurons depend on level of cytoplasmic Ca²⁺.Institute for Brain Research, All-Union Center for Mental Health Research, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 21, No. 2, pp. 247–252, March–April, 1989.     

Direct selection of Aspergillus terricola variants having different toxicity on a culture of fibroblasts

A direct method is proposed to select less toxic mutants of Aspergillus terricola on a culture of fibroblasts. The conidia are first irradiated with UV, and then are used to grow colonies on the glass surface of tubes or flasks containing medium 199. The cells of fibroblasts are added thereupon and the two cultures are being grown together for 24--48 hours. The colonies which inhibit the growth of fibroblasts to a less extent are selected using microscopy. The method can be used for primarily selection of experimentally produced mutants of Aspergillus which form fibrinolytic enzymes possessing low toxicity.     

Mechanisms of accelerating decay of cAMP-induced calcium current

The change in the decay rates of a high-threshold calcium current (I_Ca) when a depolarizing pulse is presented was investigated under conditions of an increased level of cyclic adenosine monophosphate (cAMP) in the cytoplasm of isolated snail neurons using an intracellular injection of cAMP or extracellular application of dibutyryl-cAMP. For 20 of the 38 neurons it was found that cAMP reduced the half-life of the fast and slow components of I_Ca decay by 2–2.5 times. The effect did not depend on the test-pulse potential and was reproduced with respect to a high-threshold barium current. In double-pulse experiments it was found that cAMP enhanced the effect of depolarized prepulses (V_c) on the I_Ca tested (I_t). Analysis of the I_t-V_c curve showed that cAMP enhanced both calcium- and potential-dependent inactivation of I_Ca. It was found that when the interval between the pulses changes, cAMP slows the recovery of the calcium channel from calcium-dependent inactivation. The results suggest that cAMP increases the affinity of the Ca²⁺-channel inactivation substrate for Ca²⁺-ions.Brain Institute, Russian Academy of Medical Sciences, Moscow. Translated from Neirofiziologiya, Vol. 24, No. 1, pp. 60–68, January–February, 1992.     

Dynamic changes in the response of molluscan neurons to cyclic AMP with repeated injections

Microiontophoretic injection of cAMP (but not of non-cyclic AMP) into Helix snail neurons induces rapid reversible membrane depolarization. The reversa potential of the cAMP response varies between +10 and -30 mV in different cells. The amplitude of the responses gradually increases (15 experiments), decreases (4 experiments) or remains unchanged (40 experiments) when the interval between the injections is less than 5 minutes. The identified neurons of the different preparations exhibit different types of dynamic changes in the amplitude of the responses to repeated cAMP injections. The possible role of the retaining current in the origin of the potentiation of cAMP responses was investigated. Potentiation of cAMP responses was preserved after the retaining current was switched off only in cases with no membrane depolarization due to spontaneous leakage of the substance from the microelectrode. It is suggested that potentiation or depression of cell responses to repeated cAMP injections is caused by dynamic changes in the cell cAMP system.     

Ultrasonography in the diagnosis of diffuse fibrocystic mastopathy

The breast of 160 females clinically diagnosed as having diffuse fibrocystic mastopathy and 61 females without clinical manifestations of breast diseases were echographically studied. The ultrasonographic design included measurement of the layer thickness of glandular tissue and its echodensity. In all diffuse mastopathies, including cystic one, there was over 14-mm glandular tissue thickness in all the portions of the breast or in its any quadrant, as well as glandular tissue echodensity changes which do not correspondent to the patients' age. In the control group, the thickness of a glandular layer varied with age, but it was no greater than 14 mm. Thus, the studies have demonstrated that over 14-mm glandular layer thickness and age-unspecific glandular tissue changes are the symptoms of diffuse fibrocystic mastopathy. The authors propose to include the measurement of these parameters into breast ultrasonographic methods since this allows one not only to make a more accurate diagnosis, but to clearly identify an echographic type of mastopathy.     

Comparative analysis of vestibular system development in various groups of mammals living under different environmental conditions

We have conducted for the first time a comparative study of the prenatal development of the vestibular system in representatives of pinnipeds (Phocidae, Otariidae, Odobenidae) and cetaceans (Odontoceti, Mysticeti) in comparison with terrestrial mammals. This allowed us to perform a detailed study of the structural organization of the inner ear in species with different ecological specialization, to find out adaptive aspects and stages of the formation of cochlear and vestibular structures in each of the studied species, and to correlate it with the properties of the environment. Studies on early embryogenesis of the labyrinth in cetaceans and pinnipeds, which represent a special direction in the evolution of placentates, give a significant contribution to the solution of problem about the evolutionary origin of the labyrinth in mammals studied. Sensory systems clearly demonstrate the scope of evolutionary and adaptive transformations, which appear in mammals during the transition from the terrestrial to the aquatic mode of life. At the same time, these results may provide help in understanding the general trends of the development of structure and function of the inner ear in mammals as a whole.     

Enhancement of low-threshold A-current of the neuronal membrane by vinpocetine

A low-threshold fast inactivating K+ current (I(Alth)) was recorded in isolated land snail neurons using the two-microelectrode voltage clamp method. A nootropic drug, vinpocetine, applied to the extracellular medium at a concentration of 1-100 microM potentiated I(Alth). The potentiation consisted in a rise of its peak amplitude and an increase of the half-decay time. Vinpocetine did not cause a shift of the steady-state activation and inactivation curves along the potential axis. Dibutyryl cyclic GMP (dcGMP) also increased the peak amplitude but did not change the time of current half-decay. dcAMP did not potentiate I(Alth). The possible role of K+-current potentiation in neuronal membranes in therapy of dementia is discussed.     

Induction of amnesia evoked by memory reconsolidation disruption with glutamate or serotonin receptor antagonists depends on protein synthesis activation

Effects of DNQX (ionotropic AMPA/cainate glutamate receptor antagonist) and metiotepin (serotonin receptor antagonist) and cycloheximide (protein synthesis inhibitor) on long-term memory reconsolidation processes were studied in snail Helix lucorum with definite type of food aversion conditioned reflex. DNQX or cycloheximide injected immediately before reminding disrupt retrieval of the food aversion 24 hours after conditioning, and repeated trials of learning with the same food as at initial trials did not form the food aversion 2 weeks later. Metiotepin + reminding also discrupt recalling of food aversion 24 hours after conditioning, while food aversion was repaired after repeated trials 2 weeks later. Simultaneous injections of DNQX + cycloheximide or metiotepin + cycloheximide immediately before reminding do not discrupt the food aversion. We suggest that unrecovered and recovered forms of amnesia induced by AMPA/cainate glutamate receptor antagonists or serotonin receptor antagonist, respectively, need specific protein molecules de novo.     

Cyclic Nucleotides Induce Long-Term Augmentation of Glutamate-Activated Chloride Current in Molluscan Neurons

1.Literature data indicate that serotonin induces the long-term potentiation of glutamate (Glu) response in molluscan neurons. The aim of present work was to elucidate whether cyclic nucleotides can cause the same effect. 2. Experiments were carried out on isolated neurons of the edible snail (Helix pomatia) using a two-microelectrode voltage-clamp method. 3. In the majority of the cells examined, the application of Glu elicited a Cl- -current. The reversal potential (Er) of this current lied between -35 and -55 mV in different cells. 4. Picrotoxin, a blocker of Cl- -channels, suppressed this current equally on both sides of Er. Furosemide, an antagonist of both Cl- -channels and the Na+/K+/Cl- -cotransporter, had a dual effect on Glu-response: decrease in conductance, and shift of Er to negative potentials. 5. A short-term (2 min) cell treatment with 8-Br-cAMP or 8-Br-cGMP caused long-term (up to 30 min) change in Glu-response. At a holding potential of -60 mV, which was close to the resting level, an increase in Glu-activated inward current was observed. This potentiation seems to be related to the right shift of Er of Glu-activated Cl- -current rather than to the increase in conductance of Cl- -channels. The blocking effect of picrotoxin rested after 8-Br-cAMP treatment. 6. The change in the Cl- -homeostasis as a possible mechanism for the observed effect of cyclic nucleotides is discussed.     

An unusual presentation of a malignant jejunal tumor and a different management strategy

BACKGROUND: Malignant small bowel tumors are very rare and leiomyosarcoma accounts for less than 15% of the cases. Management of these tumors is challenging in view of nonspecific symptoms, unusual presentation and high incidence of metastasis. In this case report, an unusual presentation of jejunal sarcoma and management of liver metastasis with radiofrequency ablation (RFA) is discussed. CASE PRESENTATION: A 45-year-old male presented with anemia and features of small bowel obstruction. Operative findings revealed a mass lesion in jejunum with intussusception of proximal loop. Resection of bowel mass was performed. Histopathological findings were suggestive of leiomyosarcoma. After 3-years of follow-up, the patient developed recurrence in infracolic omentum and a liver metastasis. The omental mass was resected and liver lesion was managed with radiofrequency ablation. CONCLUSION: Jejunal leiomyosarcoma is a rare variety of malignant small bowel tumor and a clinical presentation with intussusception is unusual. We suggest that an aggressive management approach using a combination of surgery and a newer technique like RFA can be attempted in patients with limited metastatic spread to liver to prolong the long-term survival in a subset of patients.