Mechanical step variability during treadmill running

The present study was designed to study intra-individual step variability measured both on vertical displacement of the body (Z) and on step time (t) parameters by means of a kinematic arm and during treadmill running. A group of 17 subjects ran successively at 60%, 80%, 100% and 140% of their maximal aerobic velocity (v _amax). The total number of steps analysed was 6116. The absolute Z step variability (Z) ranged between 5 mm and 21 mm while the absolute t variability (t) ranged between 6 ms and 40 ms. Step variabilities were due to step asymmetry (from 38.5% to 48.5% of the step variability) and to stride variability. For submaximal velocities (60%, 80%, and 100%v _amax) both t and Z were independent of velocity or body dimensions whereas differences between subjects were significant (P < 0.01) for Z. On the other hand, variabilities were significantly increased when velocity was changed from submaximal to the 140%v _amax level. Furthermore, at submaximal levels Z was linked to the subject's energy cost of running (P < 0.05). Therefore, the intra-individual step variability should not be neglected in future studies on mechanical efficiency of running and it is suggested that, to obtain a good accuracy (better than 1%,P < 0.05) on mean value and variability of the mechanical parameters, measurements should be performed on at least 32–64 consecutive steps, which corresponds to about 15 to 20 s of running.     

Indices for the role played by regional flow resistance in blood pressure reflex

Summary An index, = (r/r)/(R/R), is proposed for assessment of the relative degree of participation of a regional flow resistance in a blood pressure reflex, wherer andR are regional and total peripheral resistances respectively and 's refer to their reflexive changes. For actual computation, =I (iP – Pi)/i(IP – PI), whereI=cardiac output,i=regional flow rate,P=mean arterial pressure. When the change in cardiac output is neglegible, the above equation is simplified as =1 – Pi/iP. Another index, = g/G = (Pi – iP)/(PI – IP), is introduced for the degree of contribution of a region to a reflex, whereg andG are regional and total conductances.i = 1. Some examples of application of the indices are presented.Supported in part by a grant from the Ministry of Education of Japan.     

End-plate currents evoked by paired stimuli in frog muscle fibres

Using voltage-clamp techniques spontaneously occuring miniature end-plate currents (mepc) and nerve-evoked end-plate currents (epc) were recorded in frog glycerol-treated or cut muscle preparations. Epcs were induced by pairs of stimuli (the delay of the 2nd stimulus, t being 6 ms–30 s; one pair was delivered every 60–90 s). The decay time constant of the epc (_epc) was longer, the larger its quantal content despite the presence of active acetylcholinesterase (AChE). After treatment with anticholinesterases (prostigmine or armin, an irreversible inhibitor) this increase in _epc became more pronounced. When AChE was fully active the decay of the 1st epc ₁ was slightly faster than the decay of the 2nd epc ₂ only when the interstimulus interval was rather short (t<20 ms). Following treatment with anticholinesterases this difference between ₂ and ₁ could be determined even when t was as long as 30 s. In anticholinesterase-treated preparations was found to be inversely proportional to log t: a 50% increase in the decay time-constant of the 2nd epc occurred with t=120 ms. During continuous stimulation (10 impulses/s) _epc increased from the 1st to the 5–6th responses, but then decreased in parallel with the fall in the epc amplidude. The phenomenon of postsynaptic potentiation we observed could be readily abolished when quantal content was decreased by the presence of magnesium ions, but it was relatively unaffected when the receptor density was decreased by -bungarotoxin (-BuTX).The possible existence is discussed of two kinds of repetitive binding of ACh molecules, first, to free cholinoreceptors (a process which could be inhibited by -BuTX) and, second, to a complex of the cholinoreceptor plus one molecule of ACh (a process which is less sensitive to -BuTX blocking action).     

Quantitative and sustained suppression of renal sympathetic nerve activity by left atrial distension in conscious dogs

In order to investigate the interrelations between left atrial pressure (Pla) and renal sympathetic nerve activity (RSNA) and heart rate (HR), Pla was increased by a balloon both in conscious sham-operated and cardiac-denervated dogs. RSNA was decreased and HR was increased with increasing Pla in sham-operated dogs. The reflex changes in RSNA and HR induced by the stimulation of atrial receptors persisted for at least 15 min. There was a consistent relationship between Pla and RSNA which could be described by a single exponential equation: % RSNA = 80.0(1–e^{–0.395 Pla}), or by a linear equation when Pla was less than 6 mmHg; %RSNA=-13.5Pla–2.25. The relationship between Pla and HR can be described by a single exponential equation: HR = 86.5(1–e^{–0.125 Pla}). A significant linear relationship between RSNA and HR was obtained during a graded left atrial distention (%RSNA=-1.08HR–17.7). In cardiac-denervated dogs, RSNA tended to increase and HR remained constant during the left atrial distention. These results indicate that left atrial receptors regulate RSNA and HR in both a quantitative and sustained manner in conscious sham-operated dogs.     

Interactions of the RAD7 and RAD23 excision repair genes of Saccharomyces cerevisiae with DNA repair genes in different epistasis groups

Summary The RAD7 and RAD23 genes of S. cerevisiae affect the efficiency of excision repair of UV-damaged DNA. We have examined the UV survival of strains carrying the rad7 or rad23 deletion mutation in combination with deletion mutations in genes affecting different DNA repair pathways. As expected, the rad7 and rad23 mutations interact epistatically with the excision repair defective rad1 mutation, and synergistically with the rad6 and rad52 mutations that affect the postreplication repair and recombinational repair pathways, respectively. However, the rad7rad6 and the rad23rad6 mutants exhibit the same level of UV sensitivity as the radlrad6 mutant. This observation is of interest since, in contrast to the rad7 or the rad23 mutations, the rad1 mutant is very UV sensitive and highly excision defective. This observation suggests that RAD6 and RAD7 and RAD23 genes compete for the same substrate during DNA repair.     

Separating the direct effect of hypoxia from the indirect effect of changes in cardiac output on the maximum pressure difference across the tricuspid valve in healthy humans

In healthy humans, changes in cardiac output are commonly accommodated with minimal change in pulmonary artery pressure. Conversely, exposure to hypoxia is associated with substantial increases in pulmonary artery pressure. In this study we used non-invasive measurement of an index of pulmonary artery pressure, the maximum systolic pressure difference across the tricuspid valve (P_max), to examine the pulmonary vascular response to changes in blood flow during both air breathing and hypoxia. We used Doppler echocardiography in 33 resting healthy humans breathing air over 6–24 h to measure spontaneous diurnal variations in P_max and cardiac output. Cardiac output varied by up to ~2.5 l/min; P_max varied little with cardiac output [0.61±0.74 (SD) mmHg min l^–1]. Eight of the volunteers were also exposed to eucapnic hypoxia (end-tidal ) for 8 h. In this group P_max rose progressively from 21 mmHg to 37 mmHg over 8 h. By comparing diurnal variations in P_max during air breathing with changes in P_max during hypoxia in the same eight individuals, we concluded that only approximately 5% of the changes in P_max during hypoxia could be attributed to concurrent changes in cardiac output. The low sensitivity of P_max to changes in cardiac output makes it a useful index of hypoxic pulmonary vasoconstriction in healthy humans.     

Hypothalamic temperature during desynchronized sleep

Summary The influence of changes in heat loss at specific heat exchangers, appraised by recording ear skin temperature (Ts), on the hypothalamic temperature (Thy) rise during desynchronized sleep (DS) was studied in unrestrained cats at different ambient temperatures (Ta). The correlations of initial and final Thy changes (iThy and fThy) with initial and final Ts changes (iTs and fTs), respectively, are statistically not significant. However, a significant negative correlation was found between fiThy, i.e. fThy-iThy, and fiTs, i.e. fTs-iTs. The latter result shows that only after its initial rise is Thy affected by changes in heat loss at specific heat exchangers during DS. Accordingly, fThy and fiThy are positively correlated with Ta. However, also iThy, although not affected by heat loss changes at specific heat exchangers, shows a positive correlation with Ta. On the basis of these results and of the data in the literature, it is concluded that three independent factors underlie Thy changes during DS, namely heat loss at specific heat exchangers, hypothalamic blood flow and thermogenesis.Supported by grant No. 80.00531.04 from the National Research Council (CNR), Rome, Italy     

Influence of muscle fibre type and pedal rate on the V̇O2-work rate slope during ramp exercise

We hypothesised that the ratio between the increase in oxygen uptake and the increase in work rate (O₂/WR) during ramp cycle exercise would be significantly related to the percentage type II muscle fibres at work rates above the gas exchange threshold (GET) where type II fibres are presumed to be active. We further hypothesised that ramp exercise at higher pedal rates, which would be expected to increase the proportional contribution of type II fibres to the total power delivered, would increase the O₂/WR slope at work rates above the GET. Fourteen healthy subjects [four female; mean (SD): age 25 (3) years, body mass 74.3 (15.1) kg] performed a ramp exercise test to exhaustion (25 W min^–1) at a pedal rate of 75 rev min^–1, and consented to a muscle biopsy of the vastus lateralis. Eleven of the subjects also performed two further ramp tests at pedal rates of 35 and 115 rev min^–1. The O₂/WR slope for exercise <GET (S ₁) was significantly correlated with O₂ peak in ml kg^–1 min^–1 (r=0.60; P<0.05), whereas the O₂/WR slope for exercise >GET (S ₂) was significantly correlated to percentage type II fibres (r=0.54; P=0.05). The ratio between the O₂/WR slopes for exercise above and below the GET (S ₂/S ₁) was significantly greater at the pedal rate of 115 rev min^–1 [1.22 (0.09)] compared to pedal rates of 35 rev min^–1 [0.96 (0.02)] and 75 rev min^–1 [1.09 (0.05), (P<0.05)]. The greater increase in S ₂ relative to S ₁ in subjects (1) with a high percentage type II fibres, and (2) at a high pedal rate, suggests that a greater recruitment of type II fibres contributes in some manner to the xs O₂ observed during ramp exercise.     

Effect of menstrual cycle and gender on ventilatory and heart rate responses at the onset of exercise

To clarify the luteal-follicular and male–female differences in ventilatory and heart rate responses at the onset of exercise, seven women and seven men performed voluntary exercise and passive movement for 20 s (brief voluntary exercise and brief passive movement) and voluntary exercise for 3 min (long voluntary exercise) in a sitting position. Voluntary exercise consisted of alternate flexion-extensions of both lower legs with a weight corresponding to about 2.5% of the subjects' body mass attached to each ankle, at a frequency of about 60 times min^–1. Passive movement was carried out without weights by experimenters pulling ropes attached to both of the subjects' ankles, in the same way as voluntary exercise. During these exercises and movements, minute inspiratory ventilation (_I) and heart rate (HR) were continuously measured by breath-by-breath and beat-to-beat techniques. We calculated relative changes of _I and HR (_I and HR). Additionally, we averaged _I and HR obtained during the exercise and movement for each subject, and performed a correlation analysis between the averaged _I and HR. It was clarified that: (1) _I and HR in the follicular phase were almost equal to those in the luteal phase; (2) there were no significant male–female differences in these parameters; (3) significant positive correlations were found in both genders only during brief voluntary exercise. We conclude that ventilatory and HR responses at the onset of voluntary exercise and passive movement are not affected by the menstrual cycle or gender.     

Heat storage and body temperature during cooling and rewarming

Summary During calorimetric experiments with forced cooling and rewarming, changes in rectal temperature (T _re) and mean skin temperature ( _sk) allowed calculations of Burton's (1935) weighting coefficient a, which relates body temperature change to change in mean body temperature ( _b). Calculating _b from change in body heat content (H _b), which was determined from direct and indirect calorimetry, included individualized values for body specific heat based on body fat content. In five different cooling procedures there were two with cooling by exposure to cold water and three with cooling in a tubing suit; two of the procedures included mild exercise. The H _b ranged from –335 to –1600 kJ; rewarming restored body heat content. The mean (SEM) value of a in 119 determinations was 0.75 (0.01). This small variability in the coefficient probably came from the large values of H _b and from the use of maximal changes in _sk andT _re, including afterdrop. Change inT _re by itself correlated with _b, but with much variability. In forced body cooling and rewarming, 0.75(T _re) + 0.25 ( _sk) gives an accurate estimate of _b, hence change in body heat storage.     

Mating-type suppression of the DNA-repair defect of the yeast rad6Δ mutation requires the activity of genes in the RAD52 epistasis group

The RAD6 gene of Saccharomyces cerevisiae is required for post-replication repair of UV-damaged DNA, UV mutagenesis, and sporulation. Here, we show that the radiation sensitivity of a MAT a rad6 strain can be suppressed by the MAT2 gene carried on a multicopy plasmid. The a1-2 suppression is specific to the RAD6 pathway, as mutations in genes required for nucleotide excision repair or for recombinational repair do not show such mating-type suppression. The a1-2 suppression of the rad6 mutation requires the activity of the RAD52 group of genes, suggesting that suppression occurs by channelling of post-replication gaps present in the rad6 mutant into the RAD52 recombinational repair pathway. The a1-2 repressor could mediate this suppression via an enhancement in the expression, or the activity, of recombination genes.     

Amino acids 519–524 of Dictyostelium myosin II form a surface loop that aids actin binding by facilitating a conformational change

Residues 519–524 of Dictyostelium myosin II form a small surface loop on the actin binding face, and have been suggested to bind directly to actin through high affinity hydrophobic interactions. To test this hypothesis, we have characterized mutant myosins that lack this loop in vivo and in vitro. A mutant myosin in which this loop was replaced by an Ala residue (519–524/+A) was non-functional in vivo. Replacement with a single Gly residue instead of Ala yielded partial function, suggesting that structural flexibility, rather than hydrophobicity, is the key feature of the loop. The in vivo phenotype of the mutant enabled us to identify a number of additional amino acid changes that restore function to the 519–524/+A mutation. Intriguingly, many of these, including L596S, were located at some distances away from the 519–524 loop. We have also isolated suppressors for the L596S mutant myosin, which was not functional in vivo. The suppressors for 519–524/+A and those for L596S showed complementary charge patterns. In ATPase assays, 519–524/+A S1 showed very low activity and little enhancement by actin, whereas L596S S1 was hyper active and displayed enhanced affinity for actin. In motility assays, 519–524/+A myosin released actin filaments upon addition of ATP and was unable to support movements. L596S myosin was also inactive, but in this case actin filaments stayed immobile even after the addition of ATP. Transient kinetic measurements demonstrated that 519–524/+A S1 is not only slower than wild type to bind actin filaments, but also slower to dissociate from actin filaments. Based on these results, we concluded that the 519–524 loop is not a major actin binding site but aids actin binding by facilitating a critical conformational change.     

Differential cardiorespiratory response to combined exercise with different combinations of forearm and calf exercise

The purpose of this study was to examine whether cardiorespiratory responses to combined rhythmic exercise (60 contractions · min^–1) was affected by different combinations of upper and lower limb exercise in seven healthy women. Six different rhythmic exercises were compared: 6-min rhythmic handgrip at 10% of isometric maximal voluntary contraction (MVC) (H10); 6-min rhythmic plantar flexion at 10% MVC (P10); exhausting rhythmic handgrip at 50% MVC (H50); exhausting rhythmic plantar flexion at 50% MVC (P50); H50 was added to P10 (P1OH50); and P50 was added to H10 (H10P50). Exercise duration, after handgrip was combined with plantar flexion (P10H50), was shorter than that of H50, although the exercise duration of HIOP50 was not significantly different from P50. No significant difference was found between the difference from rest in oxygen uptake ( O₂) during H10P50 and the sum of O₂ during H10 and P50. Also, the differences from rest in forearm blood flow ( FBF) and calf blood flow ( CBF) during H10P50 were not significantly different from FBF in H10 and from CBF in P50. In contrast, O₂ in P10H50 was lower than the sum of O₂ in P10 and H50 (P < 0.05), and J FBF in P10H50 was lower than that in H50 (P < 0.05) , while CBF was not significantly different between P1OH50 and P10. The changes in heart rate from rest (d HR) during the combined exercises were lower than the sums of HR in the corresponding single exercises (P < 0.05). These results demonstrated an inhibitory summation of several cardiorespiratory responses to combined exercise resulting in a reduction in exercise performance which would seem to occur easily when upperlimb exercise is added to lower limb exercise.     

Processing of binaural stimuli by cat superior olivary complex neurons

Summary A method was developed to record stereotactically from the cat Superior Olivary Complex (SOC) using glass micropipettes. Sound stimulation was given through a closed system that permitted independent variation of interaural time (time) and intensity (int) differences. The most common binaural units found (n = 34) were ipsilateral excitatory, contralateral inhibitory (EI¹), cells of the Lateral Superior Olive (LSO). Some Medial Superior Olive (MSO) cells and presumed MSO ascending afferents were found but, as noted by other authors, we found it difficult to obtain single unit recordings from this nucleus. The LSO EI cells were mostly sensitive to higher frequencies and showed Peristimulus Time Histograms (PSTHs) consisting of a sharp On response followed by a plateau when stimulated with Best Frequency (BF) tone bursts or noise bursts. This On response was sensitive to time and int such that ipsilateral time lead or intensity increase resulted in a stronger response. The response reached a minimum around zero time or int. No sharp peaks or dips were seen in the physiological range needed for localization, instead the response increased with increasing ipsilateral lead or intensity to the maximum values tested (2048 s time, 30 dB int). In the physiological range the time and int response were complementary (both increasing response as ipsilaterality was increased). Provided enough sound energy in the unit's sensitive region was present, the same time curves were produced when BF tone bursts, masked tone bursts, sharp onset tone bursts or noise bursts were used. Changing the time of the carrier of the tone burst alone had no effect (except for one cell with a BF of 560 Hz), only the relative time of arrival of the stimulus envelope seemed to be important. In contrast to these LSO EI cells MSO-type units showed EI or EE predominantly low frequency phase-locked responses. When stimulated with interaurally phase shifted (pha) BF tones the unit response was a cyclic function of pha. Some cells (all that were tested, n = 6 including the 560 Hz LSO EI cell) showed these cyclic responses when stimulated with noise bursts or non-BF tones. However, these characteristic delays were not necessarily in the physiological range, i.e. we could find no evidence that these units were responding to time/pha values corresponding to a particular sound source direction. In both LSO and MSO it seems that integration of information higher in the CNS from a population of these cells is necessary for unambiguous coding of sound source direction. The time intensity trading ratios measured in two MSO type cells (11 and 26 /dB) were clearly different to those measured in LSO EI cells (n = 6, 99–550 s/dB). These ratios correspond approximately to those of the psychophysical time and int images measured by Hafter and Jeffress (1968).Supported by the Deutsche Forschungsgemeinschaft (SFB 45)     

Plasma catecholamines and heart rate at the beginning of muscular exercise in man

Summary The relationship between the time course of heart rate and venous blood norepinephrine (NE) and epinephrine (E) concentrations was studied in 7 sedentary young men before and during 3 bicycle exercises of 5 min each (respectively 23±2.8%, 45±2.6% and 65±2.4% , mean ±SE). During the low level exercise the change in heart rate is monoexponential ( =5.7±1.2s) and no increment above the resting level of NE (NE) or of E (E) occurs. At the medium and highest intensity of exercise: a) the change in heart rate is biexponential, for the fast and the slow component averaging about 3 and 80 s respectively; b) NE (but not E) increases continuously with time of exercise; c) at the 5th min of exercise heart rate increments are related to NE; d) between 20s and 5 min, at corresponding sampling times, the heart rate of the slow component is linearly related to NE. At exercise levels higher than 33% the increase in heart rate described by the slow component of the biexponential kinetic could be due to an augmented sympathetic activity revealed by increased NE blood levels.     

Effects of the order of running and cycling of similar intensity and duration on pulmonary diffusing capacity in triathletes

To study the pathophysiological mechanisms involved in the decrease of post-triathlon diffusing capacity (DLco), blood rheologic properties (blood viscosity: _b; changes in plasma volume: PV) and atrial natriuretic factor (ANF) were assessed in ten triathletes during cycle-run (CR) and run-cycle (RC) trials at a metabolic intensity of 75% of maximal oxygen consumption (O_2max). The DLco was measured before and 10 min after trials. ANF and PV were measured at rest, after the cycle and run of CR and RC trials, and at the end of and 10 min after exercise. RC led to a greater DLco decrease, a lower ANF concentration and a lower PV than did CR, whereas for both CR and RC _b was increased throughout exercise and 10 min after. In addition, after CR the DLco decrease was inversely correlated (r=–0.764; P<0.01) with PV. The association of decreased plasma volume, increased _b, and lower ANF concentrations after RC suggested that lower blood pulmonary volume may have caused the greater decrease in Dlco as compared with CR. The inverse correlation between PV and DLco reinforces the hypothesis that fluid shifts limit the post-exercise DLco decrease after the CR succession in triathletes. Lastly, cycling in the crouched position might increase intra-thoracic pressure, decrease thorax volume due to the forearm position on the handlebars, and weaken peripheral muscular pump efficacy, all of which would limit venous return to the heart, and thus result in low pulmonary blood volume. Compared with cycling, running appeared to induce the opposite effects.     

Continuous recording of intrapulmonary “Compressed air” as a sensitive noninvasive method of measuring bronchial obstruction in guinea pigs

The method presented is based on whole-body plethysmography. The apparatus consisted of two chambers (a=respiratory, b-body chamber) separated by a tight water-filled rubber cuff which was fixed around the head of the animal. Experiments were performed under constant gas conditions: temperature 30°C, 100% relative humidity, the volumes of the two chamber being identical. Volume changes in the chamber (V _a, V _b) were recorded continuously by means of pressure transducers. Respiratory flow was calculated by differentiation of V _a with respect to time. The three parameters V _a, V _b and respiratory flow allowed the calculation of breathing frequency, inspiration/expiration ratio, (peak) expiratory flow and specific airway conductance. In addition we describe a new parameter indicating bronchial obstruction: a graphical plot of V _b against V _a produces a closed loop, the area of which reflects the degree of airway obstruction, and we read off the parameter we term compressed air from this graph. In our hands this parameter was more than ten times as sensitive as other measures of bronchial obstruction. Using this new technique we have carried out pharmacological studies with eicosatetraynoic acid (ETYA), 2-aminomethyl 4-t-butyl-6-iodophenol (MK 447=radical scavenger), the histamine₁ antagonist elemastine and the histamine₂ antagonist cimetidine. In allergen-tested animals we observed mild protective effects of ETYA when given as an aerosol (3 mg) and pronounced effects of MK 447 (4 mg i.p.). Combined H₁H₂-antagonism was much more effective in preventing allergen-induced bronchial obstruction than H₁-antagonism alone.Supported by Deutsche Forschungsgemeinschaft (Do 240/1)     

Antiandrogentherapie der pathologisch gesteigerten und abartigen Sexualität des Mannes

Zusammenfassung Mit 100 mg Cyproteronacetat (1.2-Methylen-6-chlor-^4,6-pregnadien-17-ol-3.20-dion-17-acetat) pro Tag per os konnten innerhalb von 10–14 Tagen Libido und Potenz hypersexuell bzw. abartig sexuell erregter Männer unabhängig vom Lebensalter in bisher 17 behandelten Fällen ohne Therapieversager und ohne wesentliche Nebenwirkungen gehemmt werden.

---

Summary With 100 mg Cyproteroneacetate (1.2-methylene-6-chloro-^4,6-pregnadiene-17-ole-3.20-dione-17-acetate) orally applied per day libido and potency of men suffering from hyper- or abnormal sexuality were inhibited within 10 to 14 days independent from the age of the patients in 17 cases up to this time without any failure in therapy and without fundamental side effects.

     

Hypomethylation of the human HLA-DRα gene in breast carcinomas and autologous metastases

The methylation pattern of the human HLA-DR gene was analyzed in normal breast tissues, breast primary tumors and lymphonodal metastases isolated from patients carrying breast carcinomas. In breast adenomas and also in normal tissues (including breast, muscle, brain, sperm and T- and B-lymphocytes), the HLA-DR gene is hypermethylated at the CCGG and GCGC sites. In all tissues studied, the only constantly unmethylated region is located in the 5 portion of the gene, near the promoter sequence. Further, the results indicate that the HLA-DR gene is hypomethylated in carcinomas and in the relative metastatic lymph nodes. It is suggested that hypomethylation of the human HLA-DR gene could be proposed as a molecular marker of malignant breast tumors.     

Bidirectional active transport of thiosulfate in the proximal convolution of the rat kidney

Using the standing droplet method in the late proximal convolution and simultaneous microperfusion of the peritubular capillaries, the zero net flux transtubular concentration difference of thiosulfate at 45 s was determined, the latter being taken as a measure of active thiosulfate transport. Under control conditions, in the presence of Na⁺, near zero c values were observed. When 1 mmol/l carinamide or paraaminohippurate (PAH) were added to the perfusates significant reabsorptive c arose. However, when 7.5 mmol/l sulfate was added to the Na⁺-free secretory c values were observed. Tested under Na⁺-free conditions, the secretory c was not influenced by simultaneously present 5 mmol/l of SO ₄ ^2– but was diminished by 50 mmol/l SO ₄ ^2– . PAH (1 mmol/l), carinamide (0.2 mmol/l) and probenecid (1 mmol/l) decreased the secretory c by 48, 65 and 48%, respectively. The PAH secretion was not influenced, when thiosulfate or sulfate up to 50 mmol/l was added to both perfusates. Under Na⁺-free conditions the c of thiosulfate in early loops of the proximal convolution is higher than in late loops, while for PAH this pattern is reversed. Taken together with the previously published inhibition of sulfate reabsorption by thiosulfate the data indicate 1. thiosulfate is reabsorved by the Na⁺-dependent sulfate transport system and 2. thiosulfate is simultaneously secreted by a carinamide-, probenecid-and PAH-sensitive secretory system. The secretory system might also be shared by sulfate. The thiosulfate net flux is the result of the difference in the activity of the counteracting transporters, located at the luminal and contraluminal cell side. Is is possible that the higher activity of the transporter at one cell side leads to a reversal of the flux through the transporter at the other cell side.