Microfilarial periodicity in Mastomys natalensis

The microfilarial level in the peripheral blood of Mastomys natalensis infected with the filarial parasites, Litomosoides carinii, Brugia pahangi, B. malayi and Dipetalonema viteae was monitored at two-hour intervals for 24 hours. The microfilariae of B. pahangi and B. malayi exhibited nocturnal and diurnal subperiodicity, respectively; no such periodicity was seen in L. carinii and D. viteae infections. The level of B. pahangi and D. viteae microfilariae in peripheral blood was significantly increased when the host was anaesthetized with diethylether or pentothal sodium. Ether-induced anaesthesia had no effect on the level of B. malayi microfilariae but pentothal was most effective. The peripheral blood count of L. carinii microfilariae tended to decrease in the anaesthetized animals but the reduction was not statistically significant.     

Occurrence of microfilariae in various hollow organs and in the peritoneal cavity after treatment of Litomosoides carinii infected Mastomys natalensis with diethylcarbamazine and haloxon

Treatment of Litomosoides carinii infected Mastomys natalensis with diethylcarbamazine (DEC: 500 mg/kg p.o.) was followed by increased occurrence of microfilariae in the bronchi of the host after 40 min and lasting at least until 6 h after treatment. After 4 h, increased levels of larvae were observed in the gut. Only a few microfilariae occurred in the bladder and sputum. Accumulations of microfilariae were found furthermore in the Lnn. hepaticae whereas no changes were observed in the inguinal or jejunal and lung and pleura associated lymph nodes. Increased numbers of microfilariae were found in the peritoneal cavity only after 8 and continuing until at least 48 h after treatment. In contrast, after haloxon treatment (100 mg/kg p.o.) an accumulation of microfilariae was found in the peritoneal cavity only, following a time course similar to that after DEC.     

Immunity to Litomosoides carinii in Mastomys natalensis. I. Effect of immunization with microfilariae and existing primary infections on the parasitaemia after microfilariae injection and challenge infection

Subcutaneous injections of intrauterine stages of Litomosoides carinii into Mastomys natalensis induced strong immunity to i.v. injected blood microfilariae. Immunity, developed after boostering with an i.p. and an i.v. injection of microfilariae, did not totally suppress the parasitaemia of a challenge infection but reduced significantly the microfilaraemia level. No effect was found on number and size of the worms of the challenge infection, the number of microfilariae or the number of leucocytes in the pleural cavity. Delayed type hypersensitivity reactions in challenged animals were similar to those in non-immunized, infected controls. Sera of immunized animals agglutinated microfilariae and mediated cell attachment to microfilariae. Challenge infections did not change this until the end of the fourth week post infection but sera taken 32 days after challenge and later failed to induce such reactions. Challenge infections performed 120 or 240 days after a primary infection did not increase the parasitaemia of recipients. Dissections carried out 130 days after the challenge showed that (a) the developmental rate of the challenge infection was reduced by about 50%; (b) the size of the challenge parasites was reduced; and (c) that these worms produced significantly less embryonic stages in comparison to worms of primary infections, of which about 90% were abnormal.     

Histamine metabolism of gastric carcinoids in Mastomys natalensis.

Pharmacological inhibition of gastric acid secretion and subsequent hypergastrinemia in Mastomys natalensis is an experimental model well suited for the study of gastric carcinoid formation. The genetic susceptibility of Mastomys to develop such tumors is a feature reminiscent of the situation in patients with the MEN-1 Zollinger Ellison syndrome, in whom tumor-induced hypergastrinemia, promotes the development of gastric carcinoids. Chronic hypergastrinemia, induced by the irreversible H2-receptor antagonist loxtidine will cause carcinoid formation in Mastomys already after four to six months. As in humans, gastric carcinoids in Mastomys are mainly composed of enterochromaffinlike (ECL) cells and have low malignant potential. Administration of exogenous gastrin to normal young animals increases the expression of histidine decarboxylase (HDC) mRNA in the oxyntic mucosa within 30 minutes. Endogenous hypergastrinemia, induced by short-time loxtidine treatment (three to 29 days) enhances the expression of HDC mRNA, histamine contents and ECL cell numbers in the oxyntic mucosa. Long-term loxtidine treatment (seven to 21 months) results in sustained hypergastrinemia and tumor formation. Tumor-bearing animals exhibited an increase in HDC mRNA and histamine content in the oxyntic mucosa as well as increased urinary excretion of the main histamine metabolite, tele-methylimidazole acetic acid (MeImAA). Subsequent to cessation of loxtidine treatment for two weeks, all parameters of histamine metabolism were normalized in tumor-bearing animals. These results indicate that gastric carcinoids developing during hypergastrinemia are well-differentiated neoplasms whose histamine synthesis and metabolism is regulated by plasma gastrin.     

Immunity to Litomosoides carinii in Mastomys natalensis. II. Effects of chemotherapeutically abbreviated and postpatent primary infections on challenges with various stages of the parasite

Naive Mastomys natalensis, Litomosoides carinii-infected M. natalensis at a postpatent stage of the infection and L. carinii-infected M. natalensis treated chemotherapeutically with furazolidone (FUR), FUR and diethylcarbamazine (FUR/DEC) or amoscanate (AMOS) were challenged by either injection or implantation of 40 third stage larvae (L3, s.c.), 40 fourth stage larvae (L4, 16 days old, i.p.), 20 male and 20 female preadult worms (36 days old, i.p.), 12 adult female worms (i.p.) or 6 X 10(6) microfilariae/kg (i.v.). Microfilaraemia in animals challenged at a postpatent stage (independent of the kind of challenge), was either totally suppressed or at least greatly reduced. Necropsy of L3-challenged animals showed that neither the length of the worms nor their content of morphologically intact, intrauterine stages was affected. Infected, treated animals challenged with developing stages (L3, L4 and preadult worms) showed reduced levels of microfilaraemia (by up to 75%). Dissection of AMOS-treated, L3-challenged animals showed that both the developmental rate and the fertility of the worms were affected. Microfilaraemia was also reduced after implantation of adult worms into treated animals. This was independent of the interval between treatment and challenge (44-150 days) except in animals challenged 10 days after AMOS-treatment, which showed no difference from naive controls. However, infected, treated M. natalensis, cotton rats and gerbils did not develop immunity against intravenously injected blood microfilariae.     

Hepatic microsomal alterations during Dipetalonema viteae infection in Mastomys natalensis

The multimammate rat, Mastomys natalensis was used as a model system to evaluate the chronic effects of infection by Dipetalonema viteae on hepatic mixed function oxidase activity. Total hepatic cytochrome P450 content and related total tissue mixed function oxidase activity were decreased to about 50% of control levels at patent phase of infection. The decrease in total tissue mixed function oxidase activity was due to a large decrease in cytochrome P450 concentration in the endoplasmic reticulum. Although the decrease in total liver monooxygenase activity in two substrates aniline and aminopyrine roughly paralleled the loss in cytochrome P450 content, several other microsomal enzyme markers not related to cytochrome P450 monooxygenation were elevated in proportion to total liver microsomal protein content. These results suggest that in M. natalensis during experimental filariasis, there is proliferation of hepatic cells with normal content of endoplasmic reticulum. Furthermore, there appears to be selective toxicity for hepatic cytochrome P450 and related monooxygenase activities. This may compromise the animal's ability to metabolize and dispose of other drugs to which the animals may be exposed in the course of infection.     

Effect of picroliv on glutathione metabolism in liver and brain of Mastomys natalensis infected with Plasmodium berghei.

Administration of picroliv, the active principle from Picrorhiza kurrooa, at a dose of 6 mg/kg, po for two weeks showed significant protection against changes in liver and brain glutathione metabolism of Plasmodium berghei infected Mastomys natalensis. The depletion of reduced glutathione level and inhibition of glutathione-S-transferase, glutathione reductase and glutathione peroxidase activities due to P. berghei infection were markedly recovered by picroliv. The increased levels of lipid peroxidation products in damaged tissues were also reduced along with the recovery of glutathione metabolism.     

A mitochondrial phylogeographic scenario for the most widespread African rodent,Mastomys natalensis

In order to evaluate the contribution of geological, environmental, and climatic changes to the spatial distribution of genetic variation of Mastomys natalensis, we analysed cytochrome b sequences from the whole distribution area of the species to infer its phylogeographic structure and historical demography. Six well‐supported phylogroups, differentiated during the Pleistocene, were evidenced. No significant correlation between genetic and geographic distances was found at the continental scale, and the geographic distributions of the observed phylogroups have resulted from extensive periods of isolation caused by the presence of putative geographic and ecological barriers. The diversification events were probably influenced by habitat contraction/expansion cycles that may have complemented topographic barriers to induce genetic drift and lineage sorting. According to our results, we propose a scenario where climate‐driven processes may have played a primary role in the differentiation among phylogroups. © 2013 The Linnean Society of London     

Role of free radicals in Plasmodium berghei infected Mastomys natalensis brain.

Lipid peroxide, lipid hydroperoxide, reduced glutathione, oxidised glutathione, lipofuscin contents and the activity of the enzyme superoxide dismutase were assessed in P. berghei infected M. natalensis brain. The results showed significant increase in the levels of lipid peroxides, lipid hydroperoxides and lipofuscin in brain subcellular fractions of P. berghei infected M. natalensis. Furthermore, a depressed superoxide dismutase activity was observed along with regulation in glutathione content. An elevated level of lipid peroxidation products along with depressed activity of scavengers in brain during malaria highlights the role of free radicals in malarial pathology.     

Time courses of antibody levels in Mastomys natalensis after infections with Litomosoides carinii, Dipetalonema viteae, Brugia malayi or B. pahangi, Determined by ELISA

Using a Litomosoides carinii adult antigen, time courses of antibody levels were followed by an ELISA in L. carinii, Dipetalonema viteae, Brugia malayi and B. pahangi infected Mastomys natalensis. Using various groups of infected animals, periods up to 400 days after infection were covered. In L. carinii infected Mastomys, antibodies were first detected 11 days p.i. and levels increased rapidly until day 40. Temporarily reduced levels about the beginning of patency were followed by increasing values until about 100 days p.i. Then the antibody content of the sera remained more or less constant until about 250 days p.i. although maximum levels were found at day 170. Thereafter, the antibody concentration in the sera declined slowly but high levels were still observed 390 days p.i. The antibody content was usually higher in animals with high microfilariae densities than in those with low microfilariae counts but relations could not be proven statistically. In D. viteae infected Mastomys, maximum antibody values were reached within the beginning of patency. Levels were not altered markedly until about 110 days p.i. Thereafter they decreased slightly but then remained constant until the end of the investigation period 350 days p.i. B. malayi infected animals showed a rapid increase of the antibody content in the sera; a maximum was reached by 20 days after the infection. Thereafter, somewhat constant levels were found for 4--5 months. After 300 days p.i. the antibody levels declined progressively, accompanied with increasing parasitaemia densities; after 380 days the levels reached about 2/3 of the maximum. However, despite this, no relation was found between the levels of parasitaemia and antibody in individual animals. In B. pahangi infections the main prepatent antibody increase occurred during week 5 p.i., when maximum values were observed. The beginning of patency and the early patency were accompanied with slightly declining antibody levels. From 150 days p.i. until the end of the investigation 400 days p.i., the antibody content of the sera was fairly constant.     

Receptors for gastrin on gastric carcinoid tumor membrane of Mastomys natalensis

Specific binding sites for human gastrin I (gastrin) were identified in a crude membrane preparation from the gastric carcinoid tumor of Mastomys (Praomys) natalensis. The binding of 125I-gastrin to the carcinoid tumor membrane was saturable, and Scatchard analysis of the data revealed a single class of binding site with a dissociation constant of 139.2 pM and a maximal binding capacity of 23.5 fmol/mg protein. Gastrin and CCK8 equipotently and dose-dependently displaced the binding of 125I-gastrin to the membrane. GTP but not ATP decreased 125I-gastrin binding to the membrane, and removal of Mg2+ attenuated this inhibitory action of GTP. The GTP-induced reduction of 125I-gastrin binding was found to be due to a decrease in binding affinity without a change in binding capacity. These results clearly indicate the presence of specific binding sites for gastrin, probably coupled to guanine nucleotide-binding protein, in the carcinoid tumor membrane of Mastomys, and suggest that gastrin has possible biological actions on these tumors.     

Effects of predation and dispersal on Mastomys natalensis population dynamics in Tanzanian maize fields

1. We investigate the effects of different levels of predation pressure and rodent dispersal on the population dynamics of the African pest rodent Mastomys natalensis in maize fields in Tanzania. 2. Three levels of predation risk were used in an experimental set-up: natural level (control), excluding predators by nets and attracting avian predators by nest boxes and perch poles. Because dispersal of the rodents could mask the predation pressure treatment effects, control and predator exclusion treatments were repeated with enclosed rodent populations. 3. Population growth during the annual population rise period was faster in the absence of predators and peak population size was higher, but otherwise dynamics patterns were similar for populations where predators had access or were attracted, indicating that compensatory mechanisms operate when rodents are exposed to high levels of predation risk. Reducing dispersal of rodents removed the effect of predation on population growth and peak size, suggesting that local predators may play a role in driving rodent dispersal, but have otherwise little direct effect on population dynamics.     

Morphological and histochemical study of the submandibular gland in Praomys (Mastomys) natalensis

The submandibular gland in female and male Praomys (Mastomys) natalensis (a South African multimammate rodent) was studied using light microscopy and techniques for the demonstration of carbohydrates. Hematoxylin and eosin stain revealed the presence of a single secreting component that gave a strongly positive PAS reaction. Limiting elements of the granular tubules gave a weakly positive PAS reaction. Acidic glycoproteins were evidenced only in granules of the acinar component.