Schistosoma mansoni: Cercarial degradation of a radioactively labeled collagen gel

The apparent penetration activity of Schistosoma mansoni cercariae was quantified by means of an in vitro assay with a radioactively labeled Type I collagen gel. Both live cercariae and cercarial preacetabular gland secretions degraded the collagen. The addition of skin lipid or linoleic acid to the gel surface enhanced the degradation by live cercariae.     

Direct infection of hepatocytes by sporozoites of Plasmodium berghei

To identify the unknown liver cell type initially invaded by sporozoites of mammalian malaria, young rats were inoculated intravenously with large numbers of Plasmodium berghei sporozoites obtained from infected Anopheles stephensi mosquitoes. Fine structural studies of liver specimens obtained from the rats within 2 min after inoculation demonstrated the presence of morphologically unaltered sporozoites in the cytoplasm of hepatocytes. Many sporozoites were also observed undergoing cytolysis within the lysophagosomes of Kupffer cells, as well as other phagocytic cells. These observations strongly suggest direct infection of the hepatocyte by the sporozoite.     

Interrelation of Two Forms of Ferredoxin-NADP+ Reductase with Different Molecular Weights

The heavier form of ferredoxin-NADP⁺ reductase was extractedfrom spinach leaves or chloroplasts and isolated as the majorfraction at high ionic strengths with ammonium sulfate or sodiumchloride. At low ionic strengths, the form with the higher molecularweight was relatively unstable and was converted gradually intothe lower form. We concluded that the enzyme exists in vivoas the form with the higher molecular weight. ¹Present address: Market Development Department, Shionogi &Co. LTD., 5-Sagisu, Fukushima-ku, Osaka 553, Japan. (Received December 16, 1980; Accepted January 19, 1981)     

Leucocytosis in Biomphalaria glabrata sensitized and resensitized to Echinostoma lindoense

Leucocytosis was shown to occur in the pulmonate gastropod Biomphalaria glabrata exposed to the trematode Echinostoma lindoense. In these sensitized snails, the leukocyte count in the hemolymph was elevated 3 to 5 days postexposure to miracidia, and prior to complete encapsulation of sporocysts. This increase continued 1 to 5 days after destruction of sensitizing, irradiated E. lindoense sporocysts. Counts returned to normal levels after this period. A significant and more rapid increase in numbers of circulating leukocytes occurred 1 to 6 hr after reexposure of snails to a sensitizing dose of nonirradiated E. lindoense sporocysts. The leukocyte counts usually returned to normal levels after this period, except in snails in which some resensitizing sporocysts remained alive.     

Some observations on the morphological evidence for mechanism of the bile secretion

The morphological evidence of the intracellular route of bile secretion was investigated in the liver of goldfish (Carassius auratus) as revealed by electron microscopy. Smooth surfaced tubules or cisterns within or adjacent to the Golgi apparatus showed linear saccular forms and contained sparse particulate or cloudy materials of low electron density. The isolated vacuoles were restrictedly found between the Golgi apparatus and the intracellular bile canaliculus or hepatocytic side at the zone of transition. These vacuoles showed no reaction for acid phosphatase activity, and contained only a few cloudy materials similar to those found in the saccular tubules and within the bile canaliculus. Some of these vacuoles fused with the luminal cytolemmas of the bile canaliculus. Bases on these findings, it was assumed that these vacuoles are structures participating in transport and secretion of bile constituents and derive from the linearly sacculated tubules or cisterns in the Golgi zone. Duct cells showed no morphological evidence to suggest bile secretion.     

Cellular tumorigenicity in nude mice. Role of susceptibility to natural killer cells

The athymic nude mouse is a useful animal model for assaying the neoplastic growth potential in vivo of animal cells transformed in vitro. Despite the demonstrated absence of thymus-dependent immunological functions, however, the nude mouse has now been shown to reject transplants of certain highly malignant heterologous tumors. In addition, a few transformed mammalian cell lines that exhibit all or most of the cellular phenotypes usually associated with malignancy fail to grow as tumors when injected into nude mice. In a continuing study to identify the in vitro phenotypes associated with tumor-forming ability in vivo, we investigated the role of cellular susceptibility to the naturally occurring, thymus-independent lymphocytes (natural killer or NK cells) in determining tumor induction by animal cells in nude mice. A representative collection of animal cells (ranging from normal human diploid cell strains to highly tumorigenic clonal cell lines, either transformed in vitro or derived from experimental tumors) was tested to see if the ability of cells to form tumors is consistently correlated with their susceptibility to NK cell-mediated lysis measured in vitro with splenic leukocytes from nude mice. If the physiological role of the NK cells in vivo were to recognize, and possibly to destroy, incipient tumor cells in situ, a direct association between cellular tumorigenicity and susceptibility to NK activity, might be expected. If, on the other hand, the formation of growing tumors by animal cells in nude mice depended on their ability to escape the cytolytic activity of NK cells, cellular tumorigenicity would be associated with cellular resistance to NK cells. Results obtained in this study failed to confirm either of these associations. Thus, cellular suscepbibility to NK cells, at least as determined by direct cytotoxicity assay in vitro, is not a useful predictive indicator of cellular tumorigenicity in nude mice.     

Retention of endocrine function by an insulin-secreting pancreatic islet cell tumour from Syrain hamster through serial transplantation in nude mice.

An insulin-secreting islet cell tumour of the Syrian hamster has been transplanted serially in the congenitally immune-deficient nude mouse, in order to test the potential usefulness of this mouse mutant as a graft carrier of heterologous tumours with stable differentiated phenotypes. The incidence of tumour growth was very high, and the hamster tumour retained its functional and histologic characteristics during consecutive passages in nude mice. These results show that nude mice may be useful carriers of differentiated tumours from non-inbred species including man, and for the isolation of cell lines from such tumours.     

The role of C3 as an opsonin in the early stages of infection.

In order to investigate the role of C3 in host defense in vivo, normal AKR/J mice, genetically deficient in C5, were depleted of serum C3 by the injection of purified cobra venom factor (CoVF). Concurrent with their C3 depletion, their serum opsonizing activity decreased to a level less than 20% of normal. When these mice were challenged with an intraperitoneal injection of pneumococci 2 hr after the CoVF treatment, the LD50 was from 30 to 80 times lower than the LD50 in saline-treated control animals. When the CoVF was given only 6 hr after the pneumococcal challenge, the LD50 was the same as in the control mice. If the pneumococci were first preopsonized in vitro and then injected into CoVF-treated animals, the LD50 was the same as that in control animals. These experiments demonstrate that C3 plays a significant role in vivo in the host's defense against infection and that a major part of that role is through its action as an opsonin. Furthermore, these experiments demonstrate that the role of C3 is most significant during the early stages of bacterial invasion.     

Pyronaridine–artesunate real-world safety,tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm,open-label,cohort event monitoring study

BackgroundIn Phase II/III randomized controlled clinical trials for the treatment of acute uncomplicated malaria, pyronaridine–artesunate demonstrated high efficacy and a safety profile consistent with that of comparators, except that asymptomatic, mainly mild-to-moderate transient increases in liver aminotransferases were reported for some patients. Hepatic safety, tolerability, and effectiveness have not been previously assessed under real-world conditions in Africa.Methods and findingsThis single-arm, open-label, cohort event monitoring study was conducted at 6 health centers in Cameroon, Democratic Republic of Congo, Gabon, Ivory Coast, and Republic of Congo between June 2017 and April 2019. The trial protocol as closely as possible resembled real-world clinical practice for the treatment of malaria at the centers. Eligible patients were adults or children of either sex, weighing at least 5 kg, with acute uncomplicated malaria who did not have contraindications for pyronaridine–artesunate treatment as per the summary of product characteristics. Patients received fixed-dose pyronaridine–artesunate once daily for 3 days, dosed by body weight, without regard to food intake. A tablet formulation was used in adults and adolescents and a pediatric granule formulation in children and infants under 20 kg body weight. The primary outcome was the hepatic event incidence, defined as the appearance of the clinical signs and symptoms of hepatotoxicity confirmed by a >2× rise in alanine aminotransferase/aspartate aminotransferase (ALT/AST) versus baseline in patients with baseline ALT/AST >2× the upper limit of normal (ULN). As a secondary outcome, this was assessed in patients with ALT/AST >2× ULN prior to treatment versus a matched cohort of patients with normal baseline ALT/AST. The safety population comprised 7,154 patients, of mean age 13.9 years (standard deviation (SD) 14.6), around half of whom were male (3,569 [49.9%]). Patients experienced 8,560 malaria episodes; 158 occurred in patients with baseline ALT/AST elevations >2×ULN. No protocol-defined hepatic events occurred following pyronaridine–artesunate treatment of malaria patients with or without baseline hepatic dysfunction. Thus, no cohort comparison could be undertaken. Also, as postbaseline clinical chemistry was only performed where clinically indicated, postbaseline ALT/AST levels were not systematically assessed for all patients. Adverse events of any cause occurred in 20.8% (1,490/7,154) of patients, most frequently pyrexia (5.1% [366/7,154]) and vomiting (4.2% [303/7,154]). Adjusting for Plasmodium falciparum reinfection, clinical effectiveness at day 28 was 98.6% ([7,369/7,746] 95% confidence interval (CI) 98.3 to 98.9) in the per-protocol population. There was no indication that comorbidities or malnutrition adversely affected outcomes. The key study limitation was that postbaseline clinical biochemistry was only evaluated when clinically indicated.ConclusionsPyronaridine–artesunate had good tolerability and effectiveness in a representative African population under conditions similar to everyday clinical practice. These findings support pyronaridine–artesunate as an operationally useful addition to the management of acute uncomplicated malaria.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03201770","term_id":"NCT03201770"}}NCT03201770.

Gaston Tona Lutete and co-workers report on safety and effectiveness of the antimalarial drug pyronaridine-artesunate in African countries.