Some aspects of Phlebotomus papatasi (Scopoli) in greater Cairo, Egypt

Exogenous and indigenous cases of zoonotic cutaneous leishmaniasis are reported in several Egyptian Governorates particularly those in the Nile Delta, Phlebotomus paptasi (Scopoli) is the only proven insect vector. This paper was intended to study the seasonal abundance, nocturnal activity and breeding sites as well as other relevant behaviour aiming to throw some light on this insect vector. The results showed that: (a) the seasonal activity started in April and ended in November or beginning of December. (b) female outnumbered male indoors (7.4:1) and V.V. outdoors (0.14:1). (c) blood fed females were 97.7% indoors and 29.4% outdoors. (d) the nocturnal activity ranged between 6 p.m. to 6 a.m. indoors and 8 p.m. to 6 a.m. outdoors. (e) the immature stages of Phlebotomus were successfully recovered from rodent burrows and poultry sheds.     

Optimised dietary regimens for the laboratory maintenance of Phlebotomus langeroni nitzulescu (Diptera: Psychodidae)

The optimal feeding conditions for laboratory colonies of Phlebotomus langeroni, the vector of infantile visceral leishmaniasis in Egypt, were investigated. Sugarmeals were offered only before bloodmeals (the SB regimen), only after blood (BS), or both before and after blood (SBS). In each regimen, three different solutions of sucrose (10%, 30% and 50%, w/v) were tested as the source of sugarmeals. In general, the concentration of sucrose used had no significant effect on female longevity, although the longest lived females were those fed on 30% sucrose. Females on the BS regimen were the longest lived whereas those on the SB were the shortest lived. Sucrose concentration did not significantly affect total fecundity, the number of eggs oviposited by females, or the proportion of each egg batch that remained unlaid, but female flies fed 30% sucrose laid more eggs than those fed 10% or 50%, and SBS females laid more eggs than SB or BS. Sucrose concentration and dietary regimen both significantly affected the proportion of laid eggs that hatched, 30% sucrose giving significantly higher proportions than 10% or 50% (in all tested regimens), and the SBS regimen producing higher proportions than the SB or BS. Provision of 30% sucrose before and after bloodmeals is therefore recommended for the laboratory maintenance of P. langeroni.     

Phlebotomus papatasi saliva inhibits protein phosphatase activity and nitric oxide production by murine macrophages

Leishmania parasites, transmitted by phlebotomine sand flies, are obligate intracellular parasites of macrophages. The sand fly Phlebotomus papatasi is the vector of Leishmania major, a causative agent of cutaneous leishmaniasis in the Old World, and its saliva exacerbates parasite proliferation and lesion growth in experimental cutaneous leishmaniasis. Here we show that P. papatasi saliva contains a potent inhibitor of protein phosphatase 1 and protein phosphatase 2A of murine macrophages. We further demonstrate that P. papatasi saliva down regulates expression of the inducible nitric oxide synthase gene and reduces nitric oxide production in murine macrophages. Partial biochemical characterization of the protein phosphatase and nitric oxide inhibitor indicated that it is a small, ethanol-soluble molecule resistant to boiling, proteolysis, and DNase and RNase treatments. We suggest that the P. papatasi salivary protein phosphatase inhibitor interferes with the ability of activated macrophages to transmit signals to the nucleus, thereby preventing up regulation of the induced nitric oxide synthase gene and inhibiting the production of nitric oxide. Since nitric oxide is toxic to intracellular parasites, the salivary protein phosphatase inhibitor may be the mechanism by which P. papatasi saliva exacerbates cutaneous leishmaniasis.     

The potential effect of global warming on the geographic and seasonal distribution of Phlebotomus papatasi in southwest Asia

The distribution of Phlebotomus papatasi in Southwest Asia is thought to be highly dependent on temperature and relative humidity. A discriminant analysis model based on weather data and reported vector surveys was developed to predict the seasonal and geographic distribution of P. papatasi in this region. To simulate global warming, temperature values for 115 weather stations were increased by 1 degree C, 3 degrees C, and 5 degrees C, and the outcome variable coded as unknown in the model. Probability of occurrence values were then predicted for each location with a weather station. Stations with positive probability of occurrence values for May, June, July, and August were considered locations where two or more life cycles of P. papatasi could occur and which could support endemic transmission of leishmaniasis and sandfly fever. Among 115 weather stations, 71 (62%) would be considered endemic with current temperature conditions; 14 (12%) additional stations could become endemic with an increase of 1 degree C; 17 (15%) more with a 3 degrees C increase; and 12 (10%) more (all but one station) with a 5 degrees C increase. In addition to increased geographic distribution, seasonality of disease transmission could be extended throughout 12 months of the year in 7 (6%) locations with at least a 3 degrees C rise in temperature and in 29 (25%) locations with a 5 degrees C rise.     

Vector-host-parasite inter-relationships in leishmaniasis. I. The effect of Leishmania parasites on rate of digestion of blood proteins from various vertebrate hosts by the sand fly Phlebotomus langeroni (Diptera: Psychodidae)

Phlebotomus langeroni collected from a leishmaniasis endemic focus at Et Agamy, Alexandria, Egypt, were found to have fed on blood from man, dogs (Canis familiaris) and rats (Rattus rattus). The effect of the kind of blood meal on the development and the life-cycle of L. infantum and L. major in laboratory reared P. langeroni was therefore investigated. A membrane feeding technique was used to infect sand flies. Gut smears of infected females were examined immediately after feeding and daily for 16 days. Nectomonads and short promastigote forms of L. infantum or L. major were detected in females fed on human, dog and rat bloods at all intervals. Paramastigotes (infective stage) were present only in females fed on dog blood containing L. infantum or L. major and in those fed on rat blood containing L. major. It is concluded that among the factors influencing the Leishmania-phlebotomus relationship is the natural medium in which the parasite is present in vivo. The blood of the natural reservoir host(s) is the key factor for the development of the infective parasite form in the sand fly and P. langeroni could be considered a potential vector for transmitting L. infantum from dogs and L. major from rats and dogs but not from man. This investigation offers a new concept for the study of interactions among vector, host and parasites in Leishmania transmission.     

Fate of the promastigotes of Leishmania tropica major and L. gymnodactyli in the body of Phlebotomus papatasi under conditions of a mixed infection

We have shown that 8S and U2 fractions of low molecular weight nuclear RNA lmwn RNA) have tow stable conformational states with different electrophoretic mobilities. We have shown also that fractions UIa and UIb are conformational isomers. Fractions 8S and U2 are present only in one conformational state during electrophoresis, while UI RNA is always represented by both conformations. The conformation of lmwn RNAs is dependent upon conditions of isolation of nuclei and of extraction of RNA. It may change during storage of water solution of RNA at -20 degrees. Conformational changes discovered are not the result of degradation. Only one of two stable conformations of any lmwn RNA may be physiologically active, as it is the case of 5S rRNA and tRNAS. One ought to keep this in mind while studying the functions of low molecular weight nuclear RNAs.     

Phlebotomus papatasi sand fly salivary gland lysate down-regulates a Th1, but up-regulates a Th2, response in mice infected with Leishmania major

A vertebrate host becomes infected with Leishmania major when the sand fly vector injects parasites into skin along with saliva. Previous studies showed that salivary gland lysate of the New World sand fly Lutzomyia longipalpis markedly enhanced L. major infection in CBA mice. However, L. major is an Old World parasite transmitted in nature by the Old World sand fly Phlebotomus papatasi. Here we examine the ability of P. papatasi salivary gland lysate to enhance infection (lesion size and parasite burden) by L. major. In addition, we examine the effects of salivary gland lysate on the immune response to L. major by monitoring the levels of cytokine mRNA from the lymph nodes draining cutaneous lesions. We found that P. papatasi salivary gland lysate dramatically exacerbated lesion development in disease-resistant CBA mice. This exacerbation of disease correlated with inhibition of the production of Thl cytokines and associated factors (IFN-gamma, IL-12, and inducible nitric oxide synthase), but with enhancement of the Th2 cytokine IL-4, whereas no changes in the levels of IL-10 and TGF-beta were noted. Importantly, salivary gland lysate directly up-regulated expression of IL-4 mRNA in mice in the absence of infection with L. major.     

Calcium-activated potassium channel gene expression in the midgut of Drosophila

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are linked to both familial and sporadic human colon cancer. So far, a clear biological function for the APC gene product has not been determined. We assayed the activity of APC in the early Xenopus embryo, which has been established as a good model for the analysis of the signaling activity of the APC-associated protein beta-catenin. When expressed in the future ventral side of a four-cell embryo, full-length APC induced a secondary dorsoanterior axis and the induction of the homeobox gene Siamois. This is similar to the phenotype previously observed for ectopic beta-catenin expression. In fact, axis induction by APC required the availability of cytosolic beta-catenin. These results indicate that APC has signaling activity in the early Xenopus embryo. Signaling activity resides in the central domain of the protein, a part of the molecule that is missing in most of the truncating APC mutations in colon cancer. Signaling by APC in Xenopus embryos is not accompanied by detectable changes in expression levels of beta-catenin, indicating that it has direct positive signaling activity in addition to its role in beta-catenin turnover. From these results we propose a model in which APC acts as part of the Wnt/beta-catenin signaling pathway, either upstream of, or in conjunction with, beta-catenin.     

Epithelium formation in the Drosophila midgut depends on the interaction of endoderm and mesoderm

The reorganization of mesenchymal cells into an epithelial sheet is a widely used morphogenetic process in metazoans. An example of such a process is the formation of the Drosophila larval midgut epithelium that develops through a mesenchymal-epithelial transition from endodermal midgut precursors. We have studied this process in wild type and a number of mutants that show defects in midgut epithelium formation. Our results indicate that the visceral mesoderm serves as a basal substratum to which endodermal cells have to establish direct contact in order to form an epithelium. Furthermore, we have analyzed the midgut phenotype of embryos mutant for the gene shotgun, and the results suggest that shotgun directs adhesion between midgut epithelial cells, which is independent from the adhesion between endoderm and visceral mesoderm.     

Behavioral effects of infectious diseases: Phlebotomus fever in man.

Employed the synthetic work technique to assess the behavioral effects of a self-limiting viral infection, Phlebotomus (Sandfly) fever. Average efficiency, as measured with the mean percentage of base line performance, fell about 18 and 25% with 2 groups of 8 experimental Ss each as compared with 4 uninfected controls. These are not as great as the 25-33% decrements in performance previously observed in more severe cases of bacterial infection with respiratory Pasteurella tularensis (Rabbit fever or tularemia). Ss differed greatly in their behavioral reactions to infection, ranging from essentially no decrement to maximum decrements of about 14% (Sandfly fever) and 20% (tularemia) of base line performance per degree rise in body temperature during the febrile period. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Historical note on the discovery of cutaneous leishmaniasis transmission by Phlebotomus]

Compared to the past, modern dentistry offers a wide range of treatment options to the public. These options are more likely to be appreciated and accepted when we take the feelings of our patients into account. Dr. T. J. Murray, a former dean of Dalhousie University's medical school, says: "I believe it is just as important now, in the era of scientific medicine and dentistry, to practise the art of our profession as it ever was. Our professions were always a balance of caring and healing. In modern times, the concepts and approaches to healing have had a scientific underpinning, but they have not supplanted the need for humanistic care. In fact, many persons have problems and illnesses that are not amenable to scientific treatment or cure, and the approach is for caring, understanding, explanation, reassurance, and 'being there' for the patient."     

Multicentric primary adenocarcinomas of the midgut: the first case report

Multicentric adenocarcinomas of the midgut have not been described; even multiple adenocarcinomas limited to the small intestine are extremely uncommon, with only 14 cases reported in the literature. We report a case of multicentric synchronous involvement of the entire midgut with adenocarcinoma in a 52-yr-old Polish woman who had more than 30 lesions extending from duodenum to mid-transverse colon. There was no family history of cancer. Preoperative evaluation and intraoperative exploration were negative for primary malignancy of the lungs, breasts, ovaries, pancreas, and other parts of the gastrointestinal tract. Results of histopathological examination, immunohistochemical staining, and ras mutational analysis of the lesions uniformly support the diagnosis of multicentric poorly differentiated adenocarcinoma. The cause for this unusual presentation is unknown, although sporadic genetic alteration(s) of oncogene(s) might have been the precipitating event.     

Immunohistological localization of regulatory peptides in the midgut of the female mosquito Aedes aegypti

The midgut of the female mosquito Aedes aegypti was studied immunohistologically with antisera to various regulatory peptides. Endocrine cells immunoreactive with antisera to perisulfakinin, RFamide, bovine pancreatic polypeptide, urotensin 1, locustatachykinin 2 and allatostatins A1 and B2 were found in the midgut. Perisulfakinin, RFamide and bovine pancreatic polypeptide all react with the same, about 500 endocrine cells, which were evenly distributed throughout the posterior midgut, with the exception of its most frontal and caudal regions. In addition, these antisera recognized three to five neurons in each ingluvial ganglion and their axons, which ran longitudinally over the anterior midgut, as well as axons innervating the pyloric sphincter. The latter axons appear to be derived from neurons located in the abdominal ganglia. Antisera to two different allatostatins recognized about 70 endocrine cells in the most caudal area of the posterior midgut and axons in the anterior midgut whose cell bodies were probably located in either the brain or the frontal ganglion. Antiserum to locustatachykinin 2 recognized endocrine cells present in the anterior midgut and the most frontal part of the posterior midgut, as well as about 50 cells in the most caudal region of the posterior midgut. Urotensin 1 immunoreactivity was found in endocrine cells in the same region as the perisulfakinin-immunoreactive cells, but no urotensin-immunoreactive axons were found in the midgut. Double labeling experiments showed that the urotensin and perisulfakinin immunoreactivities were located in different cells. Such experiments also showed that the locustatachykinin and allatostatin immunoreactivities in the most caudal area of the posterior midgut were present in different cells. No immunoreactivity was found in the mosquito midgut when using antisera to corazonin, allatropin or leucokinin IV. Since these peptides have either been isolated from, or can reasonably be expected to be present in mosquitoes, it was concluded that these peptides are not present in the mosquito midgut.     

Implication of the midgut of the centipede Lithobius forficatus in the heavy metal detoxification process

The ability of two rat liver fatty acid binding protein (L-FABP) isoforms to influence microsomal phosphatidic acid biosynthesis, a key intermediate in glycerolipid formation, and phospholipid fatty acid remodeling was examined in vitro. Isoform I enhanced microsomal incorporation of [1-14C]-oleoyl-CoA into phosphatidic acid 7-fold while isoform II had no effect relative to basal. In contrast, isoform II enhanced microsomal incorporation of [1-14C]-palmitoyl-CoA into phosphatidic acid 4-fold while isoform I had no effect. These results suggest that each L-FABP isoform selectively utilized different acyl-CoAs for glycerol-3-phosphate esterification. Both isoforms stimulated phosphatidic acid formation by increasing glycerol-3-phosphate acyltransferase activity, not by increasing lysophosphatidic acid acyltransferase activity. Furthermore, the effects of L-FABP on phosphatidic acid biosynthesis could not be correlated with protection from acyl-CoA hydrolysis. L-FABP isoforms also influenced phospholipid fatty acid remodeling in a phospholipid-dependent manner. Isoform I preferentially enhanced oleate and palmitate esterification into phosphatidylethanol-amine, while isoform II stimulated esterification into phosphatidylcholine, phosphatidylserine and sphingomyelin. Taken together, these data demonstrated a unique role of each L-FABP isoform in modulating microsomally derived phospholipid fatty acid composition. (c) 1998 Elsevier Science B.V.     

Does duodenal atresia and stenosis prevent midgut volvulus in malrotation?

The risk-benefit balance when aspirin is compared with aspirin combined with ticlopidine is being investigated in several multicentre trials (MUSIC and WEST II versus TASTE, MUST, and STARS respectively). Cardiologists follow one of two strategies. Some prefer a more aggressive antiplatelet regimen, disregarding the risk of neutropenia (0.7%) because they want to avoid lessening the therapeutic effect of vessel patency obtained with stent implantation. Others give only aspirin (a money saving approach) confident that IVUS inspection (an expensive approach) will allow an adequate evaluation of full stent expansion and lesion coverage, despite a more pronounced activation of the coagulation cascade. Our impression so far is that the combination of ticlopidine and aspirin has a more favourable risk-effect balance.     

Nuclease digestion in between and within nucleosomes

In the course of digestions of rat liver nuclei with micrococcal nuclease the size of the nucleosomal DNA is shortened by 50-60 nucleotide pairs from starting lengths of about 200, 400, 600, 800, etc. nucleotide pairs in the monomeric and oligomeric nucleosomes, respectively. Acid soluble DNA material is created relatively slowly as compared to the rate of formation of subnucleosomal material. More DNA with lengths in between the 200, 400, etc. nucleotide pairs of nucleosomal DNA is formed when digestions with micrococcal nuclease are carried out at 0 to 10 degrees C compared to 40 degrees C. With DNAase II, on the other hand, formation of a 200 nucleotide pair pattern is favoured at the low temperatures. Apparently, the accessibility of potential cleavage sites in between and within nucleosomes depends strongly on the conditions of digestion. Possible reasons for this dependence are discussed.     

Molecular systematics of Phlebotominae: a pilot study. Paraphyly of the genus Phlebotomus

Phylogenetic relationships among Phlebotominae were inferred through a pilot study using parsimony analysis of the D2 domain of ribosomal DNA sequences: 455 pairs of bases were sequenced in nine species of Phlebotomine sandflies which belong to the genera Lutzomyia, Phlebotomus and Sergentomyia. Two taxa are used as outgroups: Psychoda sp. and Nemapalpus flavus which is the sister group of the Phlebotominae. The South American genus Lutzomyia appears to be monophyletic. The Mediterranean species Sergentomyia dentata is its sister group and is not clustered with the Old World genus Phlebotomus. The latter is a paraphyletic genus with an early individualization of the branch including the closely related subgenera Phlebotomus and Paraphlebotomus, and a late individualization of the subgenus Larroussius. These results have some consequences on the biogeography of the leishmaniasis in the Old World.     

Secretory patterns of tryptophan metabolites in midgut carcinoid tumor cells

Hormonal overproduction is a significant problem in patients with disseminated midgut carcinoid tumors. Serotonin (5-HT) is one major product secreted from such tumors and the urinary excretion of its metabolite (5-hydroxyindoleacetic acid, 5-HIAA) serves as an important tumor marker. The present study aimed at elucidating mechanisms of tryptophan metabolite secretion to facilitate the treatment of the carcinoid syndrome. When midgut carcinoid tumors were studied in primary cell cultures, several similarities with adrenergic neurons could be demonstrated. A marked dose-dependent depletion of intracellular 5-HT could be induced by reserpine, and monoamine oxidase-activity was revealed both in functional studies and by immunocytochemistry. Differences between tumors in the ratios of tryptophan metabolites released indicated that enzymes for synthesis and degradation of 5-HT were individually expressed. Treatment with the somatostatin analogue octreotide or with dexamethasone decreased the extracellular levels of tryptophan metabolites, but the mechanisms were partly different. In some tumors octreotide also decreased the synthesis of 5-HT, while dexamethasone markedly increased the intracellular 5-HIAA levels. It is of clinical interest to further elucidate these mechanisms, since the two drugs may have complementary actions in carotid crisis reactions.