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PubMed1991

Additional force during stretch of single frog muscle fibres following tetanus.

Single fibres from the anterior tibialis muscles of frogs were used in paired difference experiments to investigate the long-term effect (up to 3.8 s) of tetanic stimulation on fibre stiffness during relaxation. The fibres were stretched from sarcomere lengths of 2.5 microns to 3.0 microns at constant velocities for periods ranging from 0.5 to 1.75 s. The first stretch of each pair took place when the fibres had not experienced a tetanus for at least 5 min. The second stretch took place 20-30 s after the first, but it was preceded by a tetanus (100 Hz stimulation applied for 190 ms; temperature, 23 degrees C). The force produced by the first stretch was subtracted from the force produced by the second to produce a paired difference. The fibres were held at the sarcomere length of 3.0 microns except for a brief period of time immediately prior to the stretches (1200 or 1450 ms). During those periods the fibres were shortened to 2.5 microns (250 ms) and then held at 2.5 microns, regardless of whether a tetanus was elicited, for either 950 or 1200 ms. The second stretch of each pair began either at the end of, or 250 ms after, the last stimulating pulse of the tetanus. At every velocity of stretch, the force produced by the fibres during the stretches was greater when the stretches were preceded by a tetanus than when they were not, and the additional force peaked at the conclusion of the stretches. The additional force, which was produced during the stretches following the tetani, declined for the remainder of the data acquisition period (up to 3 s) following the completion of stretches; it extrapolated to zero at 7-8 s after the completion of the stretches. The magnitude of the additional force was a non-linear direct function of the rate of stretch. Thixotropy or an increased stiffness to stretch was observed in all of the fibres following periods of quiescence.

Animals↗
PubMed1986

Effect of tetanus duration on the free calcium during the relaxation of frog skeletal muscle fibres.

Single fibres were dissected from the tibialis anterior muscle of the frog and injected with the photoprotein aequorin. Tension and the light emission of the injected aequorin (a function of the free intracellular calcium concentration) were recorded both at rest and during tetanus relaxation. The level of light emission from resting single fibres corresponded to a free intracellular calcium concentration ([Ca2+]i) of 100 nM (+/- 40 nM, n = 4). The time course of the decline in light was examined during the three periods of muscle relaxation: period 1 during the slow phase of tension relaxation, period 2 during the exponential phase of relaxation and period 3 after the completion of force relaxation. The time course of the decline in light (after a correction for the kinetics of the aequorin reaction) showed that [Ca2+]i declines exponentially with a rate constant of 25 s-1 (+/- 1.7, n = 3) after a single stimulus at 10 degrees C. With increasing tetanus duration, the rate of decline of [Ca2+]i decreased during period 1. It is suggested that this decrease in the rate of decline of [Ca2+]i results from an intracellular calcium buffer (which takes up calcium in parallel with the sarcoplasmic reticulum) becoming loaded with calcium during the tetanus. Throughout period 2 [Ca2+]i was elevated above resting levels. The level of [Ca2+]i during this period varied from fibre to fibre but could be as high as 1 microM. The mean level of [Ca2+]i during this period also depended on the tetanus duration. A long-lasting elevation in [Ca2+]i was observed during period 3, [Ca2+]i returning towards resting levels with an approximately exponential time course. During this period the level of [Ca2+]i (at a given time after the last stimulus) depended on the tetanus duration. It is suggested that this long-lasting elevation in [Ca2+]i reflects the release of calcium from the intracellular calcium buffer described above. The results suggest that the rate of decline of [Ca2+]i after a few seconds of tetanic stimulation can be explained by the rate of calcium sequestration by the sarcoplasmic reticulum. The increased rate of decline of [Ca2+]i after shorter periods of stimulation may be explained by the presence of a buffer that takes up calcium in parallel with the sarcoplasmic reticulum. The later release of calcium from this buffer gives rise to the long-lasting elevation in [Ca2+]i during period 3. The slow kinetics of calcium binding and release by this buffer appear compatible with published data on the kinetic properties of parvalbumin.

Aequorin↗
PubMed1981

Inhibition of tetanus tension by elevated extracellular calcium concentration.

Extracellular [Ca2+] in the range of 5-20 mM produces a concentration-dependent reversible reduction in tetanus tension in single frog skeletal muscle fibers. Both peak tension and ability to sustain tension during tetanus is reduced. The effect is unrelated to osmotic effects and independent of stimulation frequency in the range 100-200 Hz. The effect occurs both at 8 and 24 degrees C. Tetanus tension is most strongly inhibited by elevated extracellular [Ca2+] at short muscle lengths, but the effect can be seen at all lengths. Microelectrode recordings during tetanus indicate that action potentials remain undiminished in amplitude and duration throughout the tetanus. The evidence suggests that the inhibition results from a failure of action potentials propagation within the transverse tubular system.

Action Potentials↗
PubMed2000

Mechanisms involved in tetanus-induced potentiation of fast IPSCs in rat hippocampal CA1 neurons.

In the present study, possible mechanisms involved in the tetanus-induced potentiation of gamma-aminobutyric acid-A (GABA-A) receptor-mediated inhibitory postsynaptic currents (IPSCs) were investigated using the whole cell voltage-clamp technique on CA1 neurons in rat hippocampal slices. Stimulations (100 Hz) of the stratum radiatum, while voltage-clamping the membrane potential of neurons, induces a long-term potentiation (LTP) of evoked fast IPSCs while increasing the number but not the amplitude of spontaneous IPSCs (sIPSCs). The potentiation of fast IPSCs was input specific. During the period of IPSC potentiation, postsynaptic responses produced by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride and baclofen, GABA-A and GABA-B agonists respectively, were not significantly different from control. CGP 36742, a GABA-B antagonist, blocked the induction of tetanus-induced potentiation of evoked and spontaneous IPSCs, while GTPgammaS, an activator of G proteins, substitution for GTP in the postsynaptic recording electrode did not occlude potentiation. Since GABA-B receptors work through G proteins, our results suggest that pre- but not postsynaptic GABA-B receptors are involved in the potentiation of fast IPSCs. A tetanus delivered when GABA-A responses were completely blocked by bicuculline suggests that GABA-A receptor activation during tetanus is not essential for the induction of potentiation. Rp-cAMPs, an antagonist of protein kinase A (PKA) activation, blocks the induction of potentiation of fast IPSCs. Forskolin, an activator of PKA, increases baseline evoked IPSCs as well as the number of sIPSCs, and a tetanic stimulation during this enhancement uncovers a long-term depression of the evoked IPSC. Sulfhydryl alkylating agents, N-ethylmaleimide and p-chloromercuribenzoic acid, which have been found to presynaptically increase GABA release and have been suggested to have effects on proteins involved in transmitter release processes occurring in nerve terminals, occlude tetanus-induced potentiation of evoked and spontaneous IPSCs. Taken together our results suggest that LTP of IPSCs originates from a presynaptic site and that GABA-B receptor activation, cyclic AMP/PKA activation and sulfhydryl-alkylation are involved. Plasticity of IPSCs as observed in this study would have significant implications for network behavior in the hippocampus.

Alkylation↗
PubMed1976

The myocardial energetic active state. I. Oxygen consumption during tetanus of cat papillary muscle.

The potential role of active state maintenance as a determinant of myocardial oxygen consumption (MVO2) has not been defined. Right ventricular papillary muscles from 15 cats were studied in a polarographic myograph at 23 degrees C in a Krebs-Ringer solution containing 7.5 mM Ca2+ and 10 mM caffeine. MVO2 was determined for isometric tetani at Lmax of 1-5 seconds' duration. Increases in tetanus duration related linearly to increments in both active tension time (delta active tension) and MVO2. In order to examine the oxygen cost of active state maintenance not attributable to associated tension generation, both the same isometric and 2.5- to 10.0-second lightly preloaded isotonic tetani were produced in nine muscles. For each tetanus duration the contribution throughout the contraction of developed force (preload) to MVO2 could be subtracted from overall isotonic MV02. In the absence of the MVO2 associated with force development, the active state duration was related linearly to MVO2, with a mean active state MVO2 of 2.42 +/- 0.29 nl O2/mg dry muscle/sec of isotonic tetanus; this MVO2 is 68% of the value of 3.58 +/- 0.42 nl O2/mg dry muscle/sec that was obtained for isometric tetanus at Lmax. This study identifies active state maintenance as the major determinant of MVO2 during myocardial tetanus and, furthermore, suggests the possibility that alterations in ative state intensity and duration may be the biochemical mechanism by which other determinants of MVO2 act in a more physiological setting.

Animals↗
PubMed1996

[Analysis of neonatal tetanus mortality in Brazil]

This study reports mortality from neonatal tetanus in Brazil (1979-1987), based on an analysis of death certificates. The distribution of causes of death in time and space was used as an indicator of proportional neonatal mortality from tetanus. Underreporting remains a serious problem, particularly in northern and northeastern Brazil. In most municipalities, only one death was notified during the period under consideration, thus highlighting the importance of considering the theoretical approach of "sentinel events" in the control of this disease. A proportional decrease in mortality from neonatal tetanus was observed in the states of Rondônia, Pará, Sergipe, São Paulo, Paraná, and Rio Grande do Sul. It was not possible to detect an association between immunization coverage with two doses of tetanus toxoid and neonatal tetanus mortality. The reduction in the number of deliveries taking place in the home during the period studied appears to have played an important role in the reduction of neonatal deaths attributable to this cause.

Journal Article↗
PubMedDate not supplied

[Neonatal tetanus]

OBJECTIVE: Neonatal tetanus is an infection with high mortality, constituting a problem in underdeveloped countries, where there is faulty prenatal attendance. In spite of this and of the decreasing incidence of the disease in the state of Rio Grande do Sul, we report a case of neonatal tetanus identified in 1997. METHOD: We interviewed the infantacute;s mother and verified her vaccination history. We conducted a clinical examination of the newborn, anaerobic culture of umbilical stump and review of medical records. We also reviewed the literature and verified the epidemic profile of neonatal tetanus in Rio Grande do Sul.RESULTS: Healthy mother, with complete outline of tetanus vaccination 4 years ago, prenatal uncomplicated and hospital delivery. Family of good socioeconomic level, differing from the other cases notified in the State, in that most did not have prenatal care nor hospital delivery. The patient is a boy. In the 24th day of life he presented fever, cyanosis, lower and upper limbs muscle hypertonia and opisthotonos episodes. An anaerobic culture of the umbilical stump grew Clostridium tetani. He was treated with penicillin G, gentamicin, sedation and tetanus immunoglobulin. He left hospital in good conditions.CONCLUSIONS: Faulty prenatal care in underdeveloped countries is the largest risk factor for high incidence of this disease in these areas. However, in pregnant women with good socioeconomic level and prenatal care, as in the case described here, this diagnosis should not be excluded if there are suggestive signs of it.

Journal Article↗
PubMed2005

Changes of synaptic structure after long-lasting LTP induced by high and low frequency tetanus in slices of the rat visual cortex.

Synaptic ultrastructural changes after long-lasting long-term potentiation (L-LTP) induced by 2 and 100 Hz tetanus were investigated by electron microscopic and stereological approach in slices of the developing rat visual cortex (postnatal days 15~21). Both 2 and 100 Hz tetanus-induced L-LTP groups showed significant increases in synaptic interface curvature, synaptic numeric density and postsynaptic density thickness, as well as significant decreases in the cleft width, as compared with the control groups. In addition, the volume density of the active zone (AZ) was increased significantly in the 100 Hz tetanus-induced L-LTP group, but not in the 2 Hz group. The mean lateral area of individual AZ in the 100 Hz group was relatively higher than that in the 2 Hz group. These data suggest that newly formed synapses in the 100 Hz tetanus-induced L-LTP group are larger than those in the 2 Hz group and that 100 Hz tetanus might trigger reorganization or synthesis of postsynaptic cytoskeleton.

Animals↗
PubMed1992

Motor units of medial gastrocnemius muscle in the rat during the fatigue test. I. Time course of unfused tetanus.

Time course of tetanus recorded during 40 Hz stimulation was examined on 70 motor units (MUs) of medial gastrocnemius muscle in 41 rats. Three types of MUs were distinguished: slow(S), fast resistant to fatigue (FR) and fast fatigable (FF). In fast MUs of either type, the stimulation induced unfused tetanus with noticeable sag. It was found that in cases of tetani in FF MUs, the sag developed earlier than in FR MUs. Timing of tetanic peak before the sag appeared correlated with contraction time. Some fast MUs demonstrated a distinct time course of tetanus: the weakly accentuated sag appeared early and it was followed by a relatively significant rise in tetanic tension. However, in slow MUs, 40 Hz stimulation induced fused or fused-like tetani. In these MUs the sag was never observed. The obtained results indicate the relation between the sag time course in tetanus and the extent of tetanus fusing.

Animals↗
PubMed1998

A statistical model for defining priority geographic areas for the control of neonatal tetanus

We applied factor analysis to indicators of health and living conditions from Brazilian states in order to define geographic areas at potential risk for neonatal tetanus. Two factors, namely 'health profile in the rural area' and 'proportional mortality on neonatal tetanus' were selected and plotted against each other. A cluster composed of States from the Northeast plus Para and Amapa was found to include most neonatal tetanus risk areas and a low case-reporting rate. Another cluster included States from the Southeast and South and displayed a neonatal tetanus reporting rate that was compatible with that for other indicators. Espirito Santo, however, was found to be a silent productive area. The Federal District appeared alone, showing the best health conditions. Finally, the States of the Middle West and Roraima constituted the last cluster, characterized by intermediate health status and high neonatal tetanus case-reporting rate. Our results were consistent with the overall Brazilian health profile, distinguishing the North and Northeast from the South and Southeast, with the Middle West in an intermediate position.

Journal Article↗
PubMed1991

Quantitation of anti-tetanus and anti-diphtheria antibodies by enzymoimmunoassay: methodology and applications.

We have developed enzymoimmunoassays (EIA) for the quantitation of antibodies (Ab) to tetanus and diphtheria toxoids (TT, DT) using Immulon I plates coated with the appropriate toxoid. A preparation of human tetanus immunoglobulin with a known concentration of anti-TT Ab was used as calibrator of the anti-TT antibody assay. The assay of anti-DT Ab is calibrated with a pool of human sera whose anti-DT Ab concentration was determined by quantitative immunoelectrophoresis, using a horse anti-DT with known Ab concentration as calibrator. A peroxidase-conjugated anti-human IgG was used in both assays. ABTS was used as substrate, and the reaction was stopped after 1 min incubation with citric acid and the OD measured at 414 nm on a Vmax reader. The assays have been applied to a variety of clinical situations. In patients suspected of having tetanus, the quantitation of antibodies has been helpful in establishing a diagnosis. In patients with a history of hypersensitivity to tetanus toxoid, verification of the levels of anti-TT antibody may prevent unnecessary and potentially harmful immunizations. The assays have also been used for the diagnostic evaluation of the humoral immune response to TT and DT, both in pediatric patients and in immunosuppressed patients. Several non-responders have been detected, and we have recently used the assay to monitor the effects of fish oil administration on the humoral immune response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Chronic tetanus: clinical report and histochemistry of muscle.

A patient who was partially immune to tetanus developed nonfulminant tetanus after a minor injury. Manifestations of the disease persisted for over 17 months. Electrophysiologic studies revealed an absent silent period in the masseter muscle, large-amplitude F-responses, and denervation. A muscle biopsy showed neurogenic atrophy with reinnervation. This observation supports the existence of chronic tetanus and provides morphologic evidence for a peripheral action of tetanus toxin in humans.

Adult↗
PubMed1996

Risk factor for neonatal tetanus in west Burkina Faso: a case control study.

A case-control study was carried out to identify risk factors for neonatal tetanus in rural Burkina Faso. Each of the 31 cases identified prospectively were matched with two controls. Risk factors such as the instrument used to cut the umbilical cord and the qualification of the midwives were only identified in the univariate analysis. The multifactorial analysis identified factors commonly believed to be associated with neonatal tetanus: lack of mother's immunization and place of birth other than maternity clinics. However, applying karite nut butter on the umbilical cord was found to be a strong independent factor associated with neonatal tetanus. Immunization of mothers against tetanus should be enforced. Health education must take into consideration sociocultural realities of these populations.

Burkina Faso↗
PubMed1979

Electrical excitability of motoneurones in early local tetanus.

1. After injection of tetanus toxin into the gastrocnemius muscle of the cat non-synaptic excitability of motoneurones was studied in early local tetanus. Antidromic stimulation of motoneurones was performed onthe toxin-treated side and on the control side of the same cat. 2. The mean resting membrane potential of the motoneurones on the toxin-treated side did not differ from that on the control side. 3. Similarly, no differences were found as to the amplitude of the action potential and its rate of rise as well as to the size and time course of the after-hyperpolarization. 4. The mean input resistance of the motoneurones of the toxintreated side did not differ from that of the motoneurones of the control side. 5. Tetanus toxin did not change the mean refractory period and latency of antidromic responses. 6. It is concluded that the action of tetanus toxin the spinal cord cannot be explained by an action of the toxin on the electrically excitable membrane elements of the motoneurones.

Action Potentials↗
PubMed1979

The involvement of the sympathetic nervous system in tetanus.

Besides the characteristic disturbances of the motor nervous system symptoms indicating an overactivity of the sympathetic nervous system can complicate the course of severe cases of tetanus. These symptoms include fluctuating tachycardia and hypertension, electrocardiographic changes, sweating, constipation with development of paralytic ileus and metabolic disorders. These symptoms are comparable to these developing in patients with phaeochromocytoma. Elevated catecholamine levels in plasma and urine have been found in several patients with tetanus who developed these symptoms. The prolonged over-activity of the sympathetic nervous system is thought to contribute to the still considerably high mortality rate. Myocardial lesions observed at necropsy are comparable to those found in patients dying of phaeochromocytoma. These lesions are suggested to be associated with sudden death from arrhythmias or cardiac failure in patients with tetanus. For the protection of the organism against the overactivity of the sympathetic nervous system a treatment using the combination of beta-adrenergic receptor blocking agents and adrenergic neuron blocking agents has been introduced. A reduction of the mortality rate was achievable by this treatment. Experimental evidence is accumulating that the tetanus toxin affects not only the motor, but also the sympathetic and sensory neurons.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Serum antibodies to diphtheria-tetanus-pertussis vaccine components in Argentine children.

The Argentine vaccination schedule against diphtheria, tetanus and pertussis (DTP) recommends three doses of DTP vaccine at 2, 4 and 6 months of age, two boosters at 18 months and 6 years, a booster dose of tetanus vaccine every 10 years and two doses during pregnancy. To evaluate the effect of this schedule, antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) and against tetanus and diphtheria toxoids were determined by ELISA in serum samples from children (1 month to 6 years) who received different doses of DPT vaccine: 0 dose (n = 50), 1 dose (n = 25), 2 doses (n = 25), 3 doses (n = 55), first and second booster (n = 25); 25 pregnant women and their offspring, and 45 adults. High antibody levels against PT (> 140 EU/ml) and FHA (> 80 EU/ml) were recorded in mothers and in the newborn. Antibody titers against PT increased with the number of doses given and decreased with time. Full protection against tetanus (titers > 0.1 IU/ml) was observed in the group of adults (0.37 IU/ml), in mothers (4.4 IU/ml) and their newborn offspring (5.5 IU/ml), and in children after receiving the second dose of DTP vaccine (1.86 IU/ml). The immune status for diphtheria was far lower, as most of the groups lacked adequate protection. After the third dose of DTP vaccine, only 78% of the children had antibody titers above the protective level (0.1 IU/ml). Since antibody levels considered to provide full protection were only achieved after the first booster dose of DTP vaccine, the primary three-dose schedule seems to be insufficient to confer adequate immunity in all vaccinees. Because of the high proportion of non-protected adults, a booster dose of Td vaccine should be considered for this group.

Adhesins, Bacterial↗
PubMed1983

Monoclonal antibodies against tetanus toxin and toxoid.

Monoclonal antibodies against tetanus toxin and its toxoid were produced by immunizing mice with toxoid or toxin. They were measured by an enzyme-linked immunosorbent assay (ELISA), by a toxin neutralization test in mice (in vivo prevention test), and by their ability to prevent binding of 125I-toxin to brain membranes or gangliosides (in vitro prevention test). Six monoclonal antibodies obtained by immunization with toxoid (anti-toxoid 1-6) were investigated in more detail. They belonged to IgG class 1. Three of them (anti-toxoid 1, 2 and 3) recognized both toxoid and toxin as well as fragment B and the light chain of toxin, but not fragment C. Two other antibodies (anti-toxoid 4 and 5) were directed against toxoid only. Neither of them prevented toxin action in vitro or in vivo. Anti-toxoid 6 recognized toxin, toxoid and fragment C, but not light chain, and prevented toxin action in vitro and in vivo. Immunization against toxin was initiated with a toxin-antitoxin complex and boosted with toxin. We studied six antibodies in more detail, all of IgG type 2. Their KD against 125I-tetanus toxin varied from 10(-9) to 10(-10) M. Anti-toxin 2 recognized toxin, toxoid, light chain and fragment B, but not fragment C. The others reacted with toxin, toxoid and fragment C, but not with light chain or fragment B. All of them prevented toxin action in vitro and in vivo. As calculated from the maximal extinction achieved in the ELISA, tetanus toxin combined with a maximum of two different antibody molecules from our set. Gel filtration data indicate that tetanus toxin reacts with monoclonal antibodies one by one. Compared with polyclonal antiserum, monoclonal antibodies yield flatter slopes in both in vitro and in vivo prevention tests. Thus, they cannot substitute for the polyclonal antibodies in clinical situations, and cannot be calibrated in international units.

Animals↗