Life cycle ofSarcocystis tenella in sheep and dog

ForSarcocystis tenella, the second microscopic sarcocyst in sheep, the dog was shown to act as final host shedding sporocysts measuring 13.75–15.8 (14.8±0.8)×9.7–10.8 (10.1±0.4) m after a prepatent period of 8–13 days. The clinical signs and the course of experimental infections in sheep were most similar toS. ovicanis. After high doses of sporocysts sheep had temperatures up to 42° C, anaemia, and paresis; they finally died from haemorrhagic diathesis. The development ofS. tenella in sheep was studied and it resulted in microscopic cysts in the musculature that measured 300–650×20–50 m. They showed hair-like delicate protrusions of the cyst wall measuring 6–8×<0.5 m, by whichS. tenella could be clearly differentiated fromS. ovicanis from day 60 p.i. onwards. The decreasing number ofS. tenella through degeneration of cysts is suggested to be a self-cleaning process.     

Untersuchungen über die aus der Muttersporocyste auswandernden Tochtersporocysten von Schistosoma mansoni

Zusammenfassung 1. Wird Australorbis glabratus mit Schistosoma mansoni infiziert und bei 30°C gehalten, so sind 11 Tage nach der Infektion Tochtersporocysten in der Mitteldarmdrüse nachzuweisen.2. Werden Tochtersporocysten in Ringerlösung ohne Glucose gehalten, so ist 60–75 min nach der Präparation keine starke Bewegungsaktivität nachweisbar. Zusatz von Glucose zur Ringerlösung (10 mmol) verlängert die Zeit aktiver Bewegung auf etwa 300 min.3. Wenn Glucose geboten wird, beträgt der Sauerstoffverbrauch pro Sporocyste 0,96·10^–4 l/h.4. Ohne Glucose wird ein Sauerstoffverbrauch von 0,73·10^–4 l/h/Sporocyste beobachtet. Mit zunehmender Versuchsdauer wird der Sauerstoffverbrauch geringer. Das wird auf die geringer werdende Bewegungsaktivität zurückgeführt.5. In dem Ausmaß wie bei Miracidien und Cercarien findet eine Speicherung von Glykogen nicht statt.Auswandernde Tochtersporocysten sind während ihrer Wanderung auf Zufuhr von Kohlenhydraten angewiesen.6. Die Sporocysten haben ein Durchschnittsvolumen von 48000 m³. Der durchschnittliche Sauerstoffverbrauch der Sporocysten beträgt 2,00 l/mg/h.7. Während der Entwicklung der Tochtersporocysten in der Mitteldarmdrüse vermehrt sich das Parasitengewebe bei einer Temperatur von 30°C im Durchschnitt um das 150–200fache seiner Masse.

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Studies on the migrating daughter sporocysts of Schistosoma mansoniI. Aspects of their carbohydrate metabolism

Summary 1. If Australorbis glabratus is infected with Schistosoma mansoni and is maintained at 30°C, there are 11 days after infection migrating daughter sporocysts in the hepatopancreas.2. Motility of daughter sporocysts which are maintained in Ringer solution without glucose ceases 60–75 minutes after preparation. If the Ringer solution contains glucose (10 mmol) they remain active for about 300 minutes.3. The average oxygen consumption of one sporocyst in Ringer solution with glucose is 0,96·10^–4 l/h.4. The average oxygen consumption in Ringer solution without glucose is 0,73·10^–4 l/h/sporocyst. The oxygen consumption decreases with increasing time. This may be due to the decreasing motility of the sporocysts.5. The sporocysts are only very poor in carbohydrates. They do not store glycogen like miracidia and cercariae. They need supply of carbohydrates from the snail during migration to the hepatopancreas.6. Migrating daughter sporocysts have an average volume of 48 000 m³. The average oxygen consumption is 2,00 l/mg/h.7. During development of daughter sporocysts in the hepatopancreas at 30°C, there is a 150–200 fold increase of the mass of parasite tissues.

     

The developmental cycle of a species of Sarcocystis occurring in dogs and sheep,with observations on pathogenicity in the intermediate host

Summary Twelve dogs were fed mutton containing small sarcocysts, and killed 1, 3, 4, 6, 7, 10, 15, 16, 17 days after infection (DAI). Beginning 13–15 DAI sporocysts 14.7×9.0 m were passed in the faeces of the dogs killed 15–17 DAI. Histological examination showed that developing stages were most numerous in the subepithelial tissue at the tips of villi in the proximal third of the small intestine. Macrogametes containing tiny PAS+ granules, and microgametocytes with peripheral developing microgametes were present 1 DAI. By 4 DAI oocysts, with a small nucleus and vacuolate cytoplasm were seen. Sporulation was observed 7–10 DAI. The first nuclear division resulted in 2 polar nuclei which divided laterally, resulting in 2 sporocysts each with 2 polar nuclei. This process was repeated once more to produce 4 nucleated sporozoites in each of 2 sporocysts. PAS+ granules were seen at the periphery of sporulating oocysts and sporocysts. There was a large PAS+ granule in the mid zone of sporozoites, with a smaller granule at one tip. Numerous sporulated sporocyst pairs were present beneath the epithelium at the tips of villi in dogs killed during patency.Four lambs were inoculated orally with sporocysts passed by dogs following feeding of infected mutton. Fifteen DAI schizonts were seen in the endothelium of arteries and arterioles in many organs, but not brain. Twenty-four DAI, smaller schizonts were seen in capillary endothelium in many organs, including brain. The two other lambs died 42 and 104 DAI, after an illness characterized by anaemia and ill-thrift. Mature schizonts were found in cells in the brain 42 DAI, associated with nonsuppurative meningoencephalitis. Developing sarcocysts were found in muscle, associated with myositis. Sarcocysts in muscle 104 DAI were mature. In the brain there were degenerate cysts and mature sarcocysts, and nonsuppurative meningoencephalitis.     

Zur Feinstruktur und Entwicklung vonSarcocystis aucheniae beim Lama

Zusammenfassung Isolierte Zysten vonSarcocystis aucheniae aus dem Lama (Lama glama) wurden an einen Hund und an eine Katze verfüttert. Nur der Hund schied nach 11 Tagen für 21 Tage 13,1–15,7 (15,0±0,54)×9,0–11,3 (10,4±0,36) m große Sporozysten aus. Eine zweite Katze, die Lamafleisch erhalten hatte, das sowohl Makrozysten vonS. aucheniae als auch nur mikroskopisch sichtbare Zysten enthielt, blieb ebenfalls negativ. Die Zysten vonS. aucheniae sind von einer Primärhülle umgeben, die blumenkohlartige gefaltete Vorwölbungen in die sie umgebende Muskelfaser bildet. Die Vorwölbungen enthalten zahlreiche Mikrofilamente. Die Primärhülle besitzt außerdem viele sehr kleine bläschenförmige Einstülpungen. Die parasitierte Muskelfaser liegt in einem großen Hohlraum im normalen Muskelgewebe. Die Zystenwand vonS. aucheniae ist ähnlich strukturiert wie die vonS. gigantea des Schafes.

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Investigations on the fine structure and biology ofSarcocystis aucheniae of the llama

Isolated cysts ofSarcocystis aucheniae of the llama (Lama glama) were fed to one dog and one cat. Only the dog excreted sporocysts, measuring 13.1–15.7 (15.0±0.54)×9.0–11.3 (10.4±0.36) m after 11 days for 21 days. A second cat, which had ingested meat of a llama containing macrocysts ofS. aucheniae as well as sarcosporidial cysts visible only under a microscope also did not excrete sporocysts. The cysts ofS. aucheniae are surrounded by a folded primary cyst wall forming cauliflower-like protrusions into the muscle fibre. The protrusions contain numerous microfilaments. In addition, the primary cyst wall forms numerous tiny vesicles. The parasitized muscle fibre is located in a large cavity within the normal muscle tissue. The cyst wall ofS. aucheniae is similarly structured to that ofS. gigantea of the sheep.

     

Vorkommen und Entwicklung von 2 Sarkosporidienarten des Pferdes

Zusammenfassung In Muskelproben (Schlund, Zwerchfell, Unterzungenmuskulatur und Herz) von 200 Pferden aus dem Schlachthof München wurden 1978/79 bei 31 Tieren (15,5%) Zystozoiten (Merozoiten, Bradyzoiten) mit der Trypsinverdauung nachgewiesen. Das Herz war dabei stets parasitenfrei. Bei 3 Tieren konnten Muskelzysten in Frischpräparationen isoliert und damit differenziert werden. AlsSarcocystic equicanis wurden Zysten mit 5–11 m langen und <0,5 m dicken, haarförmigen, labilen Vorwölbungen bestimmt, während Zysten mit 2,5–4,5 m langen und 0,8–1,0 m dicken, fingerförmigen, stabilen Vorwölbungen der SpeciesS. fayeri zugeordnet wurden. Histologisch warenS. equicanis-Zysten dünnwandig, währendS. fayeri-Zysten dickwandig und häufig quergestreift erschienen.Als Endwirt für beide Arten fungiert der Hund. Die Präpatenz beträgt 11 bis 17 Tage, die Sporozystengröße einer Mischsuspension aus beiden Arten 12,0–14,4 (13,4±0,7)×9,3–10,5 (9,8±0,4) m. Bei 2 experimentell mit je 100 000 Sporozysten infizierten Ponies konnte keine klinische Erkrankung festgestellt werden. Es fanden sich aber in Frischpräparationen bzw. bei der histopathologischen Untersuchung von Biopsieproben (111., 130., 152. und 165. Tag p.i.) und Muskelproben post mortem (167. bzw. 189. Tag p.i.) neben verschiedenen Entwicklungsstadien der Zysten beider Arten auch zahlreiche gemischtzellige Entzündungsherde, hyalinschollig entartete Muskelfasern sowie degenerierte Zysten bzw. Reste der Zystenwände. In Frischpräparationen waren Muskelzysten vonS. fayeri undS. equicanis am 111. Tag p.i. differenzierbar. Das Verschwinden der Zysten wird als eine Selbstreinigung angesehen.

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Prevalence and development of twoSarcocystis spp. in the horse

The prevalence ofSarcocystis spp. in horses was investigated in a survey at the Munich abattoir during 1978/79. Muscle specimens (oesophagus, diaphragm, sublingual muscle, myocardium) were examined using tryptic digestion. Out of 200 horses 31 (15.5%) were found to be carriers of sarcocysts. No parasites were found in the myocardium. In three animals sarcocysts could be isolated and differentiated in fresh preparations. Cysts with 5 to 11 m by less than 0.5 m hairlike, unstable protrusions were classified asSarcocystis equicanis, whereas those with 2.5 to 4.5 m by 0.8 to 1.0 m fingerlike, stabile protrusions were assigned to beS. fayeri. HistologicallyS. equicanis cysts were thin-walled andS. fayeri cysts were thick-walled and often striated.For both species the dog acts as final host. A mixture of sporocysts of both species measured: 12.0–14.4 (13.4±0.7)×9.3–10.5 (9.8±0.4) m. The prepatent period is 11 to 17 days. Two ponies experimentally infected with 100,000 sporocysts each did not show clinical signs. In fresh preparations and in histopathological examinations of biopsied (111th, 130th, 152th, and 165th day post-infection (p.i.) and postmortem material (167th and 189th day p.i.) different developmental stages of sarcocysts of both species were seen and the following pathological alterations observed: circumscribed nonpurulent inflammation, moderate Zenker's degeneration of muscle fibres, and degenerated cysts, of which sometimes only parts of the cyst wall were left. In fresh preparationsS. equicanis andS. fayeri could be differentiated 111 days p.i. The observed disappearance of the sarcocysts is suggested to be a self-cleaning process.

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Herrn Prof. Dr. Dr. h.c. J. Boch zum 65. Geburtstag gewidmet     

Wesselsbron virus haemagglutination: studies with erythrocytes of various animal species at different pH and temperatures

Summary The haemagglutinating (HA) properties of the Nigerian strain of Wesselsbron virus have been investigated using erythrocytes from a wide range of animals. The results showed that Wesselsbron virus possesses HA activity when extracted using the sucrose and acetone method. The erythrocytes of goose, horse, donkey, pig, cattle, sheep, goat, monkey, man, rabbit, rat, guinea pig and chicken were agglutinated by Wesselsbron virus at different pH values (5.75–7.0) and temperatures of 4°C, room (25±2°C) and 37°C.The ability to haemagglutinate fell as pH increased, but the effect of incubation at different temperature was not marked. However, under the conditions of the experiment HA pattern was clearest at 37°C. High HA titres (1:16) were consistently obtained using goose, horse, donkey and human erythrocytes at different temperatures.     

Effects of heat acclimation of distance runners in a moderately hot environment

Summary Five distance runners (H group) performed a 60 min bicycle exercise at a load of 60–70% VO_{2 max} in a moderately hot environment (T _a: 33.5 C, 60% RH). Following a period of heat acclimation with bench-stepping at a load equal to about 25–30% VO_{2 max}, in a hot environment (T _a: 45–50 C, 30–40% RH) for 9 days, the work test was repeated. Two control subjects (R) performed the same work tests with no heat acclimation. Heat acclimation increased performance time. Rectal temperature, mean skin temperature, heart rate, and Na⁺ concentrations in sweat were lower in H and, with one exception, sweat rate was higher after heat acclimation. All H subjects demonstrated that the linear relationship between sweat rate and rectal temperature was shifted to a lower temperature (threshold shift). This shift correlated with a lowering of resting rectal temperature. The magnitude of the reduction in those two temperatures due to heat acclimation was identical. The observed improvement of work performance in moderate heat following heat acclimation to a higher temperature is attributed to a more efficient thermoregulatory mechanism.     

The effects of long warm and cold ambient exposures on food intake water intake and body weight in the capsaicin desensitized rat

Seventeen Sprague Dawley rats received, subcutaneously, 250 mg·kg^–1 of capsaicin divided into 10 increasing doses (10–50 mg·kg^–1) and administered on 7 successive days. Nine controls were treated with an isotonic saline solution using the same protocol. The rats spent, in succession, 5 weeks at 20° C, 6 weeks at 33.5° C, 6 weeks at 8° C, 4 weeks at 30° C and, finally, 5 weeks at 20° C ambient temperature. Their mean food intake (FI), water intake (WI) and body weights were recorded daily. In the 2 groups of rats, FI was inversely related to ambient temperature. However, during the first few days of the exposures, FI in treated rats was greater than controls in the warm environment and less in the cold environment. In controls, WI increased linearly with ambient temperature in the warm environment. This relation was not found in treated rats: they drank less water than controls and lost body weight. During the first days at 8° C ambient temperature, rectal temperature decreased in treated rats and two animals died.The results are similar to those described for rats with hypothalamic lesions. They may also be related to a peripheral effect of the drug.This work was supported by the Centre National de la Recherche Scientifique (C.N.R.S. L.A. 181) and by the Institut National de la Santé et de la Recherche Médicale (I.N.S.E.R.M., A.T.P. 80-79-112)     

Fine structure of the oocyst wall and excystation ofEimeria procyonis from the American raccoon (Procyon lotor)

Oocysts ofEimeria procyonis, from the American raccoon (Procyon lotor), were broken, added to a cell suspension, fixed in Karnovsky's fluid, and studied with the electron microscope. The oocyst wall has three layers: a thin electron-dense inner layer (8–15 nm), an electron-lucent middle layer (25–35 nm), and a thick outer layer (120–140 nm). The outer layer has an electron-dense inner portion and an electron-lucent outer portion that contains membrane-bound vesicles. When exposed to a trypsin-sodium taurocholate fluid, sporozoites excysted from most sporocysts which were 35–43 months old, but not from sporocysts that looked normal and were 106 months old. Excysted sporozoites measured 13–16×3–4 (mean 14.3×3.2) m, usually had two refractile bodies, and had a nucleus with a prominent nucleolus.     

Experimentelle Infektion von Kanarien mit Plasmodium cathemerium Hartman, 1927, durch den Stich infizierter Mücken (Culex pipiens L.) und durch Inokulation isolierter Sporozoiten

Zusammenfassung Bei intravenöser Inokulation konnten bereits mit 1–10 Sporozoiten Infektionen erzielt werden; die ID₆₀ lag bei ca. 50 Sporozoiten pro Vogel.Durch den Stich jeweils einer Mücke wurden 24 von 32 Kanarien (75%) erfolgreich infiziert. Nach Präpatenzzeit und Parasitämie beurteilt, wurden pro Stich zwischen 25 und 1000 Sporozoiten abgegeben. Bei der Präparation von 242 Mücken in 15 Gruppen, konnten zwischen 1,3×10³ und 13×10³ Sporozoiten pro Mücke aus den Speicheldrüsen gewonnen werden.Bei Inokula unter 2500 Sporozoiten pro Vogel zeigte die Präpatenzzeit eine deutliche Abhängigkeit von der Anzahl der inokulierten Sporozoiten. Bei Inokula zwischen 2500 und 25000 Sporozoiten unterschieden sich nach gleicher Präpatenzzeit die Parasitämiewerte deutlich. Die Unterschiede waren innerhalb des gleichen Versuchs bei einem Verhältnis der Inokula von 2:1 selbst bei nur 5 Versuchstieren pro Gruppe biometrisch signifikant.30–40 Tage nach der Infektion der Mücken nahm die Infektiosität der Sporozoiten merklich ab, doch konnten selbst mit 68–70 Tage alten Sporozoiten (von der Infektion der Mücken an gerechnet) noch 2 Kanarien erfolgreich infiziert werden.Für die Infektiosität der isolierten Sporozoiten war das verwendete Medium und dessen Temperatur von entscheidender Bedeutung.

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Experimental infection of canaries with plasmodium cathemerium Hartman, 1927, by bites of infected mosquitoes (Culex pipiens L.) and by inoculation of isolated sporozoites

Summary Intravenously inoculated 1 to 10 sporozoites were found sufficient to produce patent infections in canaries; the ID₆₀ was about 50 sporozoites per bird.By bites of one mosquito per bird 24 from 32 canaries (75 p.c.) became infected. It was concluded from the prepatent period and the parasitaemia that one mosquito gave off from 25 to 1,000 sporozoites per bite. From 1.3×10³ to 13×10³ sporozoites could be obtained from the salivary glands of one mosquito judged by dissecting 242 mosquitoes in 15 different lots.If less than 2,500 sporozoites were inoculated, the prepatent period depended strongly on the number of sporozoites inoculated. If 2,500 to 25,000 sporozoites were inoculated, different levels of parasitaemia resulted after the same prepatent period. When the proportion of the inocula was 2:1, the differences of parasitaemia were statistically significant even though only five animals per group were used.30 to 40 days after the infection of mosquitoes the infectivity of sporozoites decreased markedly, although it was possible to infect two canaries with sporozoites of mosquitoes 68 to 70 days after their infection.The infectivity of isolated sporozoites was stongly influenced by the liquid medium used in dissecting and by its temperature.

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Eine Spende der Stiftung Volkswagenwerk hat den Bau und die Einrichtung eines Biologischen Prüfungslaboratoriums beim Institut für Angewandte Chemie ermöglicht. — Die Versuche wurden von der Weltgesundheitsorganisation finanziell unterstützt.     

Metiamide—An orally active histamine H2-receptor antagonist

Metiamide has been found to be about 10 times more active than burimamide in vitro in antagonizing histamine H₂-receptors and nearly 5 times more active in vivo as an antagonist of histamine or pentagastrin-stimulated secretion. Effective oral ED₅₀ doses for inhibition have been estimated as 25 mole kg^–1 against basal secretion in rats and 16 mole kg^–1 against maximal histamine-stimulated secretion in dogs. Administration of metiamide orally daily for 90 days with doses of 1,500 mole kg^–1 to rats and 700 mole kg^–1 to dogs produced signs of kidney damage as the dominant lesion in both species. These toxic doses are roughly 60 and 44 times greater than the ED₅₀ doses in the rat and dog, respectively. These results show that metiamide has the degree of activity and safety needed for a compound to be a candidate for thorough clinical evaluation.     

What — if any — is the role of adrenergic mechanisms in histamine release from mast cells?

The effects of catecholamines on histamine release from rat peritoneal mast cells, was studied in an in vitro system. It was found that norepinephrine (10^–5–10^–3 M) exerts a significant, dose related, repressive effect on compound 48/80-induced histamine release. This effect is greatly potentiated by -antagonists and is noticeable throughout the concentration range 10^–11–10^–3 M norepinephrine. Phentolamine diminishes the repressive effect that norepinephrine shows at 10^–5 M.Norepinephrine (10^–5 M) totally inhibits the progressive histamine release induced by both compound 48/80 and strontium (10 M) in non-Ca²⁺-depleted cells. The release that is dependent on extracellular calcium is inhibited by norepinephrine.The repressive effect of norepinephrine at 10^–3 is counteracted by 5.6 mM d-glucose, 2-deoxyglucose abolishes this effect. The repression of histamine release by 10^–5 M norepinephrine is not influenced byd-glucose.These results suggest that the effects on histamine release, observed within a low concentration range of norepinephrine (<10^–3 M), may be due to -adrenoreceptor mechanisms and an interference in transmembrane calcium transport. Our data further suggest that norepinephrine at 10^–3 M may inhibit oxidative phosphorylation.Isoproterenol and epinephrine (10^–9–10^–5 M) show little effect on 48/80-induced histamine release in a normal medium. However, when calcium is excluded from the medium, histamine release is potentiated. These results seem to indicate that isoproterenol and epinephrine act by displacing intracellular calcium, making it available for the exocytosis process.     

Predicting sweat loss response to exercise,environment and clothing

Summary Metabolic heat production (M), clothing heat transfer characteristics, and the environment dictate a required evaporative cooling (E_req) from the body to maintain thermal balance. However, the maximal evaporative capacity (E_max) is dictated by vapor transfer properties of the clothing and environment. Relationships between metabolic load, environmental conditions, clothing and sweat loss were studied in 34 heat-acclimatized males categorized into four groups (eight, eight, eight, and ten subjects) and exposed to various environmental conditions (ambient temperature, 20–54 C, and relative humidity, 10–90%), three levels of metabolic rate (resting; walking 1.34 m·s^–1, level; or walking 1.34 m·s^–1, 5% grade) while wearing various clothing ensembles (shorts and T-shirts, fatigues, fatigues plus overgarment, or sweat suit). Individual groups were not exposed to all combinations. Exposures lasted 120 min: either 10 min rest — 50 min exercise — 10 min rest — 50 min exercise, or 120 min at rest. Physiological measurements included heart rate, rectal temperature, mean skin temperature, energy expenditure and sweat loss (m_sw). E_max and E_req were calculated from environmental conditions, metabolism, clothing insulation and permeability. The ratio E_req/m_sw was found to correlate with E_max and not with M. The predictive equation for sweat loss was: m_sw=18.7×E_req×(E_max)^–0.455 within the limits 50req<360; W·m^–2 and 20max<525; W·m^–2. This formula predicts sweat loss for specific work loads, climates and clothing ensembles.     

Life cycle and ultrastructure of Adelina tenebrionis (Sporozoea: Adeleidae) from Heteronychus arator (Coleoptera: Scarabaeidae)

The coccidian from the black beetle, Heteronychus arator (Fabricius), in New Zealand was identified as Adelina tenebrionis Sautet 1930. Its development occurs in the fat body of the host. Merogony produces bundles of 8–19 vermiform merozoites, which range in length from 12.0 to 24.1 m. Spherical macrogametocytes and small, vermiform microgametocytes fuse to form a zygote. Sporogony produces an oocyst 29.2–45.0 m in diameter, containing 3–13 sporocysts, 12.3–14.0 m in diameter. The life cycle takes about 46 days in an alternative host, Planotortrix excessana (Lepidoptera: Tortricidae), at 22 C. Electron micrographs of merozoites and gametocytes are presented.     

Cardiorespiratory adjustments to tethered-swimming in the horse

The cardiorespiratory and metabolic responses to various levels of tethered-swimming were evaluated in 5 sedentary horses. Cardiac output (QQ}) and heart rate (HR) correlated highly (r=0.89 and 0.94 respectively) with work effort (WE) expressed as kg pulled·kg body wt^–1·10^–2. While swimming, stroke volume (SV) was reduced at the lowest workloads, but increased with increasing WE so that at the highest workloads it had returned to the on-land standing SV. Pressures in the pulmonic as well as on both sides of the systemic circulation were considerably elevated by this form of exercise, although only mean carotid artery pressure (CAP) correlated highly (r=0.83) with WE. During tethered-swimming plasma lactic acid (LA) rose exponentially from 1 to 10 mmol·1^–1 with increasing HR over the range 150–200 beats·min^–1. Oxygen uptake ( ) increased linearly (r=0.95) from 25–112 ml·kg^–1·min^–1. over the WE range of 3.0–7.8 kg pulled·kg body wt^–1·10^–2. The aerobic capacity of the equine species would appear to be twice that of man. The greater increase in in the exercising horse cannot be explained solely on the basis of increases inQQ}. Therefore alterations in hematocrit, hemoglobin and oxygen extraction appear to play a more important role in the horse during exercise than they do in man.     

Metiamide — An orally active histamine H2-receptor antagonist

Metiamide has been found to be about 10 times more active than burimamide in vitro in antagonizing histamine H₂-receptors and nearly 5 times more active in vivo as an antagonist of histamine or pentagastrin-stimulated secretion. Effective oral ED₅₀ doses for inhibition have been estimated as 25 mole kg^–1 against basal secretion in rats and 16 mole kg^–1 against maximal histamine-stimulated secretion in dogs. Administration of metiamide orally daily for 90 days with doses of 1,500 mole kg^–1 to rats and 700 mole kg^–1 to dogs produced signs of kidney damage as the dominant lesion in both species. These toxic doses are roughly 60 and 44 times greater than the ED₅₀ doses in the rat and dog, respectively. These results show that metiamide has the degree of activity and safety needed for a compound to be a candidate for through clinical evaluation.     

Potassium channels in the basolateral membrane of the rectal gland ofSqualus acanthias

The present study examines the influences of pH and Ca²⁺ and several putative inhibitors on the basolateral K⁺ channel of the rectal gland ofSqualus acanthias. Excised membrane patches were examined using the patch clamp technique. It is shown that reduction of the calcium activity on the cytosolic side to less than 10^–9 mol/l has no detectable inhibitory effect on this channel. Conversely, increase in calcium activity to some 10^–3 mol/l reduced the activity of this channel. Variations in cytosolic pH had only a moderate effect on the current amplitude: alkalosis by one pH unit increased and acidosis reduced the single current amplitude by some 15%. Several inhibitors were tested in excised patches when added to the cytosolic side. Ba²⁺ (5·10^–3 mol/l), quinine (10^–3 mol/l), quinidine (10^–4 mol/l), lidocaine (1 mmol/l), tetraethylammonium (10 mmol/l), Cs⁺ (10 mmol/l), and Rb⁺ (20 mmol/l) all blocked this K⁺ channel reversibly. We conclude that the basolateral K⁺ channel of the rectal gland is distinct from other epithelial K⁺ channels inasmuch as it is not stimulated by Ca²⁺ directly, but that it is qualitatively similar to many other known K⁺ channels with respect to its sensitivity towards blockers.This study was supported by Deutsche Forschungsgemeinschaft Gr 480/8 and by NSF and NIH grants to the Mount Desert Island Biological Laboratory     

The influence of H1-, H2- and H3-receptors on the spontaneous and ConA induced histamine release from human adenoidal mast cells

The effects of the H₃-agonist R--methylhistamine (R--MeHA) and the H₃-antagonist thioperamide on the spontaneous and concanavalin A (ConA) induced histamine release from human mast cells were tested and compared with the effect of some H₁- and H₂-receptor active substances. R--MeHA (10^–9–10^–7 M) exerted no effect on histamine release whereas thioperamide increased the spontaneous release at 10^–6–10^–4 M but inhibited the ConA induced release in a narrow concentration range (10^–6–10^–5 M). This enhancement might be taken as an indication of the existence of H₃-receptor dependent autoregulation although presently other mechanism cannot be excluded.     

Life cycle ofSarcocystis gongyli Trinci 1911 in the skinkChalcides ocellatus ocellatus and the snakeSpalerosophis diadema

The life cycle ofSarcocystis gongyli was established and its stages were studied by means of light and electron microscopy. The life cycle of this parasite needs two hosts, the skinkChalcides ocellatus ocellatus as the intermediate host and the snakeSpalerosophis diadema as the final host. Microscopically visible sarcocysts were observed in the skeletal muscles of naturally infected skinks (infection rate, 63%). These cysts measured 60–100×200–900 m (mean, 85×600 m). Typical mature cysts were bordered by a primary cyst wall folded into long, leaf-like protrusions, which reached approximately 2.4 m in length and were never branched. The interior of the cyst contained both metrocytes and cyst merozoites that showed the typical characteristics of the Apicomplexa. Experimental transmissions of the parasite from naturally infected intermediate hosts (skinks) to final (definitive) hosts were carried out. Only the snakeSp. diadema (family Colubridae) shed fully sporulated oocysts of theIsospora type (each with two sporocysts). The prepatent period was 14 days and the patent period ended 60 days post-infection (p.i.). Gamogony and sporogony were found within the intestinal epithelial cells of the snake. Free sporocysts in fresh snake feces measured 9.1×10.6 m on average. The fine structure of the gamogonic and sporogonic stages was studied. Gamogony occurred within the first 8 days p.i., giving rise to young oocysts in the epithelial cells of the small intestine.Abbreviations A amylopectin - C conoid - CM cyst merozoites - GS ground substance of cyst interior - HC host cell - IL inner layer of oocyst wall - L lipid - MC metrocyte - MD developing merozoite - MI mitochondrion - MN microneme - MP micropore - N nucleus - NH nucleus of a host cell - NU nucleolus - OL outer layer of oocyst wall - OW oocyst wall - P polar ring - PE pellicle - PT protrusion of PW - PW prmary cyst wall - R rhoptries - RB residual body of sporocyst - S sporocyst - SP sporozoite - ST subpellicular microtubules - SW sporocyst wall - UT unthickened places of PW - ZY zygote cytoplasm     

Coupled sodium and chloride transport into plasma membrane vesicles prepared from dogfish rectal gland

A membrane fraction, rich in basal-lateral plasma membranes, was prepared from the rectal gland of the spiny dogfish,Squalus acanthias, and the uptake of²²Na into the plasma membrane vesicles was investigated by a rapid filtration technique. Sodium uptake was greatest in the presence of a chloride gradient directed into the vesicles; it was strikingly reduced when chloride was replaced with nitrate and was even slower with gluconate. If the membrane vesicles were pre-equilibrated with potassium chloride or potassium nitrate plus valinomycin, to minimize any electrical driving forces on sodium movement, the uptake of sodium was still greatest in the presence of chloride and remarkably decreased in the presence of nitrate. Furosemide, 10^–3 and 10^–4 M, decreased sodium uptake into the vesicles in a dose dependent manner only in the presence of chloride. Furthermore, saturation of sodium uptake by increasing sodium chloride concentrations was observed. The above results provide direct evidence for a coupling of sodium and chloride fluxes across the plasma membrane of the rectal gland via a cotransport system sensitive to furosemide. They support the hypothesis that chloride secretion of the rectal gland is a secondary active transport and is driven by the sodium gradient across the basal-lateral membranes of the cell.Abbreviations Dibutyryl cyclic AMP N⁶, O²-dibutyryl adenosine 3: 5-cyclic monophosphoric acid, monosodium salt - ATP adenosine triphosphate, disodium salt - Na K-ATPase, sodiumpotassium stimulated adenosine triphosphatase - Tris tris(hydroxymethyl)aminomethane - HEPES 2-(N-2-hydroxyethylpiperazin-N'yl)ethanesulphonic acid - EDTA ethylenediaminetetraacetate Deceased October 6, 1978