Unusual primary location of non-Hodgkin lymphoma in the uterine body with compressive form: About case.

INTRODUCTION: Primary non-Hodgkin's malignant lymphoma (NHML) of the uterine body is an extremely rare localization since only eleven cases have been reported in the literature. CASE PRESENTATION: We report a case of primary NHML of the uterine body discovered during a hysterectomy performed for a uterine mass. The primary character of NHML of the uterine body was retained in view of the absence of extra-genital localization in the clinical, biological and radiological workup (Ann Arbor stage IE) and there were no signs of recurrence during follow-up. The patient received anti-CD20 immunochemotherapy (rituximab-CHOP and rituximab-VCAP combinations) and at 12 months follow-up, she is in complete remission. DISCUSSION: The diagnosis of primary and isolated NHML of the uterine body is based on a clinical and further examination and regular follow-up for several months. The treatment is not codified; surgery, poly-chemotherapy and radiotherapy are the different therapeutic modalities. Rituximab-CHOP immunochemotherapy is currently the reference treatment for primary malignant lymphomas of the uterine body particularly in young patients who wish to become pregnant. The prognosis depends mainly on two factors: age and Ann Arbor stage. CONCLUSION: Primary uterine lymphomas are rare tumors of unknown etiopathogeny and of non-specific clinical presentation, the role of the various treatments remains difficult to evaluate due to the small number of published cases.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as mortality predictor of advanced stage non-small cell lung cancer (NSCLC) with COVID-19 in Indonesia.

OBJECTIVE: This study aimed to compare the mortality rate between advanced-stage non-small cell lung cancer patients (NSCLC) with and without COVID-19. This study also explores the possible laboratory characteristics used for prognostication in patients with NSCLC and COVID-19. Additionally, this study evaluated potential differences in laboratory values between the case and control groups. PATIENTS AND METHODS: This is a single-center retrospective cohort study conducted in Dharmais National Cancer Hospital, Indonesia, enrolling patients with NSCLC undergoing chemotherapy or targeted therapy between May 2020 and January 2021. All patients with NSCLC and COVID-19 in these periods were enrolled into the case group. The control group was age-matched NSCLC patients without COVID-19 that was derived from the NSCLC cohort through randomization. RESULTS: There were 342 patients with NSCLC between May 2020 and January 2021. Twenty-seven (7.9%) of the patients were infected by COVID-19. To facilitate comparison, thirty-five age-matched controls with NSCLC were selected from the cohort. The mortality rate in patients with COVID-19 was 46.2%. Eleven patients (40.7%) had severe COVID-19, of which none survived. NLR >8.35 has a sensitivity of 83.3%, specificity of 92.9%, LR+ of 12, and LR- of 0.18. The AUC was 0.946 (95% CI 0.867-1.000), p<0.001. PLR >29.14 has a sensitivity of 75.0%, specificity of 71.4%, LR+ 2.62, LR- 0.35, and AUC 0.851 (95% CI 0.706-0.996), p=0.002. Both NLR and PLR were associated with shorter time-to-mortality in the unadjusted and adjusted model CONCLUSIONS: NLR and PLR are independent predictors of mortality in COVID-19 patients with NSCLC.

Phlebotomus papatasi sand fly predicted salivary protein diversity and immune response potential based on in silico prediction in Egypt and Jordan populations.

Phlebotomus papatasi sand flies inject their hosts with a myriad of pharmacologically active salivary proteins to assist with blood feeding and to modulate host defenses. In addition, salivary proteins can influence cutaneous leishmaniasis disease outcome, highlighting the potential of the salivary components to be used as a vaccine. Variability of vaccine targets in natural populations influences antigen choice for vaccine development. Therefore, the objective of this study was to investigate the variability in the predicted protein sequences of nine of the most abundantly expressed salivary proteins from field populations, testing the hypothesis that salivary proteins appropriate to target for vaccination strategies will be possible. PpSP12, PpSP14, PpSP28, PpSP29, PpSP30, PpSP32, PpSP36, PpSP42, and PpSP44 mature cDNAs from field collected P. papatasi from three distinct ecotopes in the Middle East and North Africa were amplified, sequenced, and in silico translated to assess the predicted amino acid variability. Two of the predicted sequences, PpSP12 and PpSP14, demonstrated low genetic variability across the three geographic isolated sand fly populations, with conserved multiple predicted MHCII epitope binding sites suggestive of their potential application in vaccination approaches. The other seven predicted salivary proteins revealed greater allelic variation across the same sand fly populations, possibly precluding their use as vaccine targets.

Perception of a modular 3D print model in undergraduate endodontic education.

AIM: To evaluate a modular 3D print training dental model with embedded human teeth and electronic working length determination for undergraduate endodontic education. METHODOLOGY: Cone-beam volume tomography data of a human skull were transferred into stereolithographic (STL) data, and a customizable modular 3D print model with individually removable sextants and teeth was generated for the use in commercially available phantom heads. Each of sixty-eight students performed a complete root canal treatment on an extracted human tooth. Working lengths were determined with electronic apex locators (EAL) and verified radiographically. Subsequently, an evaluation was carried out with regard to the difficulty of the working steps access cavity preparation, working length determination, root canal preparation/irrigation and canal filling, and these steps were compared to commonly used benchtop models. Additionally, the agreement of electronic and radiographic working length determination was assessed and analysed statistically with the chi-square test. RESULTS: A total of 68 teeth (20 incisors, 26 premolars and 22 molars) with 127 root canals were treated. In total, 87% of the students considered the modular 3D print model considerably more demanding than the conventional benchtop model. Overall, 96% felt better prepared for the clinical situation, 92% felt markedly reduced stress levels during endodontic practice in the subsequent clinical courses, and 93% of the students suggested the model should be used in future preclinical endodontic training. The preradiographic use of EAL resulted in 85% of the cases having radiographically acceptable working length determination within 0-2 mm from the radiographic apex. Readings more than 2 mm from the apex or beyond were significantly more common in molars than in premolars and incisors (P < 0.05). CONCLUSIONS: The vast majority of students rated the modular 3D print training model positively despite it being more demanding. They also recommended its use in preclinical teaching and training. The model allowed a more realistic simulation of the clinical situation with a simultaneous use of EALs and led to reduced stress levels in endodontic treatment in the subsequent clinical courses.

Polyphenols and Functional Foods from the Regulatory Viewpoint.

The aim of the present article is to give a bird's eye view of polyphenols in the European legislation and its applications according to the European Food Safety Authority, particularly regarding labeling for consumer protection in the European market. Polyphenols are given much attention by consumers because of their health effects and are exploited by food producers. Consequently, a study on cases relating to claims about polyphenols cannot leave out of consideration a panoramic about the legal framework regarding European Regulations on nutrition claims. In this ambit, the general framework is the European Commission Regulation No. 1924/2006 on nutrition and health claims made on foods; it sets the basic legal rules about nutrition claims in the European Union. Because of the possible allowed use of health claims about polyphenols, many applications have been made by food business operators. At present, the use of health claims related to polyphenols in the European market is limited only to olive oil polyphenols. All other formulations so far proposed relating to other foods have been rejected by the European Authority, being judged as lacking substantial scientific evidence.

Behavioral Assessment and Blood Oxidative Status of Aging Sprague Dawley Rats through a Longitudinal Analysis.

BACKGROUND: Cognitive frailty emerges as one of the threats to healthy aging. It is in continuum with advancing of age with uncertain indicator between pathological and physiological changes. Alterations in pathways associated with the aging process have been observed including oxidative stress, lipid metabolism, and inflammation. However, the exact mechanisms leading to cognitive decline are still unclear. OBJECTIVE: This study was sought to assess the level of cognitive functions and linked with blood oxidative status during normal aging in rats. METHODS: A longitudinal study using male Sprague Dawley rats was performed starting from the age of 14 months old to 27 months old. Cognitive functions tests such as open field, Morris water maze and object recognition were determined at the age of 14, 18, 23, and 27 months old and were compared with group 3 months old. Blood was collected from the orbital venous sinus and oxidative status was determined by measuring the level of DNA damage, lipid peroxidation, protein oxidation and antioxidant enzymes activity. RESULTS: Aged rats showed declining exploratory behavior and increased in the level of anxiety as compared to the young rats. The level of DNA damage increased with increasing age. Interestingly, our study found that both levels of malondialdehyde and plasma carbonyl content decreased with age. In addition, the level of superoxide dismutase activity was significantly decreased with age whereas catalase activity was significantly increased from 18 months of age. However, no significant difference was found in glutathione peroxidase activity among all age groups. CONCLUSION: The progressions of cognitive impairment in normal aging rats are linked to the increment in the level of DNA damage.

Pretreatment with Ultrasonication Reduces the Size of Azelaic Acid-Chitosan Nanoparticles Prepared by Electrospray.

Nowadays, electrospray is becoming a favourable approach for preparing monodispersed nanoparticles. However, this approach is quite recent and requires further works to optimize control over physicochemical properties of its products. This study aimed to determine the possible effects of sonication as a pretreatment to reduce the size of azelaic acid-chitosan particle before using electrospray. The results showed that sonication treatment can produce submicron particles of azelaic acid-chitosan. By diluting the solution and increasing sonication time and amplitude, smaller particles were obtained with the smallest one at 516 nm, sized by dynamic light scattering. The pretreated solution was then electrosprayed to reduce the size of nanoparticles to 80 nm, indicating that sonication may play an important role in reducing the size of electrosprayed nanoparticles. The electrosprayed nanoparticles were nearly monodispersed and almost spherical in shape.

Population genetics analysis of Phlebotomus papatasi sand flies from Egypt and Jordan based on mitochondrial cytochrome b haplotypes.

BACKGROUND: Phlebotomus papatasi sand flies are major vectors of Leishmania major and phlebovirus infection in North Africa and across the Middle East to the Indian subcontinent. Population genetics is a valuable tool in understanding the level of genetic variability present in vector populations, vector competence, and the development of novel control strategies. This study investigated the genetic differentiation between P. papatasi populations in Egypt and Jordan that inhabit distinct ecotopes and compared this structure to P. papatasi populations from a broader geographical range. METHODS: A 461 base pair (bp) fragment from the mtDNA cytochrome b (cyt b) gene was PCR amplified and sequenced from 116 individual female sand flies from Aswan and North Sinai, Egypt, as well as Swaimeh and Malka, Jordan. Haplotypes were identified and used to generate a median-joining network, F ST values and isolation-by-distance were also evaluated. Additional sand fly individuals from Afghanistan, Iran, Israel, Jordan, Libya, Tunisia and Turkey were included as well as previously published haplotypes to provide a geographically broad genetic variation analysis. RESULTS: Thirteen haplotypes displaying nine variant sites were identified from P. papatasi collected in Egypt and Jordan. No private haplotypes were identified from samples in North Sinai, Egypt, two were observed in Aswan, Egypt, four from Swaimeh, Jordan and two in Malka, Jordan. The Jordan populations clustered separately from the Egypt populations and produced more private haplotypes than those from Egypt. Pairwise F ST values fall in the range 0.024-0.648. CONCLUSION: The clustering patterns and pairwise F ST values indicate a strong differentiation between Egyptian and Jordanian populations, although this population structure is not due to isolation-by-distance. Other factors, such as environmental influences and the genetic variability in the circulating Le. major parasites, could possibly contribute to this heterogeneity. The present study aligns with previous reports in that pockets of genetic differentiation exists between populations of this widely dispersed species but, overall, the species remains relatively homogeneous.

Effects of age on the glucoregulatory response following acute glucoprivation induced by 2-deoxyglucose (2DG) in the adrenal medulla of Sprague Dawley rats.

OBJECTIVES: Impairment in glucose homeostasis is one of the factors that may alter the feeding drive, hunger and satiety signals, which essential to maintain a sufficient level of energy for daily activities especially among the elderly. Adrenal medulla is one of the important organs that involves in glucose homeostasis through secretion of catecholamines. The catecholamines biosynthesis pathway utilizes various enzymes and protein kinases. The aims of this study are to investigate the effects of age on the biosynthetic pathway of catecholamines in adrenal medulla by determining the level of blood glucose and blood catecholamines, the gene and protein expression of biosynthetic catecholamine enzymes (TH, DBH and PNMT) as well as protein kinase substrates that involved in the phosphorylation of TH in 2DG-induced rats. METHODS: Adrenal medulla from male Sprague Dawley rats at the age of 3-months (n=12) and 24-months (n=12) were further divided into two groups: 1) treatment group with 2DG to create glucoprivation condition and 2) the vehicle group which received normal saline as control. RESULTS: The results showed that the level of glucose, adrenaline and noradrenaline were increased in response to acute glucoprivation conditions in both young and old rats. No age-related differences were found in the basal gene expression of the enzymes that involved in the catecholamines biosynthesis pathway. Interestingly the expressions of TH and DBH protein as well as the level of TH phosphorylation at Ser40, PKA, PKC and ERK1/2 substrates were higher in basal condition of the aged rats. However, contradicted findings were obtained in glucoprivic condition, which the protein expressions of DBH, pERK1/2 and substrates for pPKC were increased in young rats. Only substrate for pCDK was highly expressed in the old rats in the glucoprivic condition, while pPKC and pERK1/2 were decreased significantly. The results demonstrate that adrenal medulla of young and old rats are responsive to glucose deficit and capable to restore the blood glucose level by increasing the levels of blood catecholamines. CONCLUSION: The present findings also suggest that, at least in rats, aging alters the protein expression of the biosynthetic catecholamine enzymes as well as protein kinase substrates that may attenuate the response to glucoprivation.

Phlebotomus papatasi SP15: mRNA expression variability and amino acid sequence polymorphisms of field populations.

BACKGROUND: The Phlebotomus papatasi salivary protein PpSP15 was shown to protect mice against Leishmania major, suggesting that incorporation of salivary molecules in multi-component vaccines may be a viable strategy for anti-Leishmania vaccines. METHODS: Here, we investigated PpSP15 predicted amino acid sequence variability and mRNA profile of P. papatasi field populations from the Middle East. In addition, predicted MHC class II T-cell epitopes were obtained and compared to areas of amino acid sequence variability within the secreted protein. RESULTS: The analysis of PpSP15 expression from field populations revealed significant intra- and interpopulation variation.. In spite of the variability detected for P. papatasi populations, common epitopes for MHC class II binding are still present and may potentially be used to boost the response against Le. major infections. CONCLUSIONS: Conserved epitopes of PpSP15 could potentially be used in the development of a salivary gland antigen-based vaccine.

Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate.

Perception of content and non-content expert facilitators of PBL according to students' performance levels.

OBJECTIVE: Problem-based learning (PBL) is a student-centred learning system that involves multidisciplinary fields focused on problem solving. Facilitators of PBL are not necessarily content experts but little is known on how this concept has affected the outcomes of PBL sessions in learning Medical Biochemistry. We aimed to evaluate the impact of having the content expert as a facilitator in conducting PBL. METHODS: A total of 150 first and second year medical students from the University Kebangsaan Malaysia were interviewed with a validated set of questions to acquire their views on the roles of facilitators in PBL in learning Medical Biochemistry. Their achievement were evaluated through their essay marks derived from various PBL packages. RESULTS: All respondents agreed that PBL sessions associated with Medical Biochemistry are best appreciated when conducted by a content-expert facilitator. Their exam marks reflected well on their perception. CONCLUSION: PBL sessions related to Medical Biochemistry is best facilitated by Biochemistry lecturers as the content experts.

Profiling of human acquired immunity against the salivary proteins of Phlebotomus papatasi reveals clusters of differential immunoreactivity.

Phlebotomus papatasi sand flies are among the primary vectors of Leishmania major parasites from Morocco to the Indian subcontinent and from southern Europe to central and eastern Africa. Antibody-based immunity to sand fly salivary gland proteins in human populations remains a complex contextual problem that is not yet fully understood. We profiled the immunoreactivities of plasma antibodies to sand fly salivary gland sonicates (SGSs) from 229 human blood donors residing in different regions of sand fly endemicity throughout Jordan and Egypt as well as 69 US military personnel, who were differentially exposed to P. papatasi bites and L. major infections in Iraq. Compared with plasma from control region donors, antibodies were significantly immunoreactive to five salivary proteins (12, 26, 30, 38, and 44 kDa) among Jordanian and Egyptian donors, with immunoglobulin G4 being the dominant anti-SGS isotype. US personnel were significantly immunoreactive to only two salivary proteins (38 and 14 kDa). Using k-means clustering, donors were segregated into four clusters distinguished by unique immunoreactivity profiles to varying combinations of the significantly immunogenic salivary proteins. SGS-induced cellular proliferation was diminished among donors residing in sand fly-endemic regions. These data provide a clearer picture of human immune responses to sand fly vector salivary constituents.

Ecological and control techniques for sand flies (Diptera: Psychodidae) associated with rodent reservoirs of leishmaniasis.

BACKGROUND: Leishmaniasis remains a global health problem because of the substantial holes that remain in our understanding of sand fly ecology and the failure of traditional vector control methods. The specific larval food source is unknown for all but a few sand fly species, and this is particularly true for the vectors of Leishmania parasites. We provide methods and materials that could be used to understand, and ultimately break, the transmission cycle of zoonotic cutaneous leishmaniasis. METHODS AND FINDINGS: We demonstrated in laboratory studies that analysis of the stable carbon and nitrogen isotopes found naturally in plant and animal tissues was highly effective for linking adult sand flies with their larval diet, without having to locate or capture the sand fly larvae themselves. In a field trial, we also demonstrated using this technique that half of captured adult sand flies had fed as larvae on rodent feces. Through the identification of rodent feces as a sand fly larval habitat, we now know that rodent baits containing insecticides that have been shown in previous studies to pass into the rodents' feces and kill sand fly larvae also could play a future role in sand fly control. In a second study we showed that rubidium incorporated into rodent baits could be used to demonstrate the level of bloodfeeding by sand flies on baited rodents, and that the elimination of sand flies that feed on rodents can be achieved using baits containing an insecticide that circulates in the blood of baited rodents. CONCLUSIONS: Combined, the techniques described could help to identify larval food sources of other important vectors of the protozoa that cause visceral or dermal leishmaniasis. Unveiling aspects of the life cycles of sand flies that could be targeted with insecticides would guide future sand fly control programs for prevention of leishmaniasis.

Evaluation of the fat-tailed gerbil, Pachyuromys duprasi (Rodentia: Gerbillidae), as a new animal model for studies of Leishmania major infection and transmission.

The fat-tailed gerbil Pachyuromys duprasi is a common burrowing rodent found across the northern Sahara Desert from Morocco to Egypt. There is overlap in the geographical distribution and ecological habitats of P. duprasi, several Old World Leishmania species, and numerous sand fly vectors of Leishmania, but there are no records that document the natural occurrence of this gerbil with any species of Leishmania or phlebotomine sand fly. Experiments were conducted to determine its potential as a natural host and laboratory animal model for Leishmania major. Captive-born P. duprasi were inoculated subcutaneously (s.c.) in the tail with promastigotes or amastigotes of an Egyptian strain of L. major and monitored for signs of infection. Local swelling and erythema was visible 10-12 days after amastigote inoculation, and within 3-4 weeks swelling had increased tail widths by up to 78%. Infections progressed more slowly and less conspicuously following inoculation with promastigotes. Tissue density of amastigotes in the gerbil's tail lesions after inoculating with either stage of L. major was significantly lower than that produced in the footpads of BALB/c mice by the same parasite and incubation period. Laboratory transmission of L. major to P. duprasi by sand fly bite was demonstrated and acquisition of L. major, by bite, from tail lesions of infected P. duprasi to laboratory-reared Phlebotomus papatasi was also achieved with 10% of biting flies developing promastigote infections. The acquisition and development of L. major infections in P. papatasi after biting an infected P. duprasi and the susceptibility of P. duprasi to L. major delivered at low densities by sand fly bites indicate that fat-tailed gerbils could serve as a natural host and reservoir of L. major.

Experimental acquisition, development, and transmission of Leishmania tropica by Phlebotomus duboscqi.

We report experimental infection and transmission of Leishmania tropica (Wright), by the blood-feeding sand fly Phlebotomus duboscqi (Neveu-Lemaire). Groups of laboratory-reared female sand flies that fed "naturally" on L. tropica-infected hamsters, or artificially, via membrane feeding device, on a suspension of L. tropica amastigotes, were dissected at progressive time points post-feeding. Acquisition, retention and development of L. tropica through procyclic, nectomonad, and leptomonad stages to the infective metacyclic promastigote stage, and anterior progression of the parasites from abdominal midgut bloodmeal to the thoracic midgut were demonstrated in both groups. Membrane feeding on the concentrated amastigote suspension led to metacyclic promastigote infections in 60% of sand flies, whereas only 3% of P. duboscqi that fed naturally on an infected hamster developed metacyclics. Sand flies from both groups re-fed on naïve hamsters, but despite infections in 25-50% of membrane-fed and 2-3.5% of naturally fed flies, no skin lesions developed in the hamsters. After four months of observation these animals were euthanized and necropsied. Screening of the organs and tissue by polymerase chain reaction (PCR) that targeted the small subunit RNA gene, amplified generic Leishmania DNA from liver, spleen, bone marrow, and blood, but only from hamsters bitten by membrane-infected P. duboscqi. These results are notable in demonstrating the ability of P. duboscqi, originating from Kenya, to acquire, retain, develop, and transmit a Turkish strain of L. tropica originally isolated from a human case of cutaneous leishmaniasis. This marks the first demonstration of complete development and transmission of L. tropica by a member of the Phlebotomus subgenus of sand flies.

Tyrosine hydroxylase phosphorylation in catecholaminergic brain regions: a marker of activation following acute hypotension and glucoprivation.

The expression of c-Fos defines brain regions activated by the stressors hypotension and glucoprivation however, whether this identifies all brain sites involved is unknown. Furthermore, the neurochemicals that delineate these regions, or are utilized in them when responding to these stressors remain undefined. Conscious rats were subjected to hypotension, glucoprivation or vehicle for 30, 60 or 120 min and changes in the phosphorylation of serine residues 19, 31 and 40 in the biosynthetic enzyme, tyrosine hydroxylase (TH), the activity of TH and/or, the expression of c-Fos were determined, in up to ten brain regions simultaneously that contain catecholaminergic cell bodies and/or terminals: A1, A2, caudal C1, rostral C1, A6, A8/9, A10, nucleus accumbens, dorsal striatum and medial prefrontal cortex. Glucoprivation evoked phosphorylation changes in A1, caudal C1, rostral C1 and nucleus accumbens whereas hypotension evoked changes A1, caudal C1, rostral C1, A6, A8/9, A10 and medial prefrontal cortex 30 min post stimulus whereas few changes were evident at 60 min. Although increases in pSer19, indicative of depolarization, were seen in sites where c-Fos was evoked, phosphorylation changes were a sensitive measure of activation in A8/9 and A10 regions that did not express c-Fos and in the prefrontal cortex that contains only catecholaminergic terminals. Specific patterns of serine residue phosphorylation were detected, dependent upon the stimulus and brain region, suggesting activation of distinct signaling cascades. Hypotension evoked a reduction in phosphorylation in A1 suggestive of reduced kinase activity. TH activity was increased, indicating synthesis of TH, in regions where pSer31 alone was increased (prefrontal cortex) or in conjunction with pSer40 (caudal C1). Thus, changes in phosphorylation of serine residues in TH provide a highly sensitive measure of activity, cellular signaling and catecholamine utilization in catecholaminergic brain regions, in the short term, in response to hypotension and glucoprivation.

Expression plasticity of Phlebotomus papatasi salivary gland genes in distinct ecotopes through the sand fly season.

BACKGROUND: Sand fly saliva can drive the outcome of Leishmania infection in animal models, and salivary components have been postulated as vaccine candidates against leishmaniasis. In the sand fly Phlebotomus papatasi, natural sugar-sources modulate the activity of proteins involved in meal digestion, and possibly influence vectorial capacity. However, only a handful of studies have assessed the variability of salivary components in sand flies, focusing on the effects of environmental factors in natural habitats. In order to better understand such interactions, we compared the expression profiles of nine P. papatasi salivary gland genes of specimens inhabiting different ecological habitats in Egypt and Jordan and throughout the sand fly season in each habitat. RESULTS: The majority of investigated genes were up-regulated in specimens from Swaymeh late in the season, when the availability of sugar sources is reduced due to water deprivation. On the other hand, these genes were not up-regulated in specimens collected from Aswan, an irrigated area less susceptible to drought effects. CONCLUSION: Expression plasticity of genes involved with vectorial capacity in disease vectors may play an important epidemiological role in the establishment of diseases in natural habitats.

Virus isolations and high population density implicate Culex antennatus (Becker) (Diptera: Culicidae) as a vector of Rift Valley Fever virus during an outbreak in the Nile Delta of Egypt.

In June, 2003, Egypt's hospital-based electronic disease surveillance system began to record increased cases of acute febrile illness from governorates in the Nile Delta. In response to a request for assistance from the Egyptian Ministry of Health and the World Health Organization (WHO), the U.S. Naval Medical Research Unit No. 3 (NAMRU-3) provided assistance in identifying the cause and extent of this outbreak. Testing of human clinical samples (n=375) from nine governorates in Egypt identified 29 cases of RVF viremia that spanned the period of June to October, and a particular focus of disease in Kafr el Sheikh governorate (7.7% RVF infection rate). Veterinary samples (n=101) collected during this time in Kafr el Sheikh and screened by immunoassay for RVFV-specific IgM identified probable recent infections in cattle (10.4%) and sheep (5%). Entomologic investigations that focused in rural, rice growing villages in the Sidi Salim District of Kafr el Sheikh during August-September, 2003, collected, identified, and tested host-seeking female mosquitoes for the presence of pathogenic viruses. Three isolates of RVF virus (RVFV) were obtained from 297 tested pools of female mosquitoes and all three RVFV isolates came from Cx. antennatus (Becker). While Cx. pipiens has been considered the primary vector of RVF virus in Egypt and is often the most common man-biting species found, Cx. antennatus was the dominant species captured at the 2003 outbreak location in Kafr el Sheikh governorate. This is the first time that Cx. antennatus has been found naturally infected with RVFV in Egypt.

Effects of ivermectin on blood-feeding Phlebotomus papatasi, and the promastigote stage of Leishmania major.

Ivermectin (IVM) is a chemically modified macrocyclic lactone of Streptomyces avermitilis that acts as a potent neurotoxin against many nematodes and arthropods. Little is known of IVM's effect against either blood-feeding Phlebotomus sand flies, or the infective promastigote stage of Leishmania transmitted by these flies. We injected hamsters subcutaneously with two standard IVM treatments (200 and 400 µg/kg body weight) and allowed cohorts of Leishmania major-infected Phlebotomus papatasi to blood-feed on these animals at various posttreatment time points (4 h, 1, 2, 6, and 10 days). Infected and uninfected sand flies that bit treated and untreated hamsters served as controls. Serum levels of IVM in low- and high-dose-treated hamsters were determined at the five time points. Sand fly mortality following blood feeding was recorded at 24-h intervals and, in relation to IVM treatment, was time and dose dependent. Mortality was most rapid and greatest among infected flies that fed nearest to time of dosing. Mean survival of infected sand flies after feeding on untreated hamsters was 11.5 days, whereas that of infected sand flies that fed 4 h, 1 day, or 2 days posttreatment on high-dose-treated hamsters (400 µg/kg) was 1.6, 2.1, and 2.7 days, respectively. Infected and uninfected sand flies that blood fed 6 days following low-dose IVM treatment (200 µg/kg) still experienced significantly greater mortality (p < 0.02) than controls. Promastigotes dissected out of surviving flies that fed on IVM-treated hamsters showed typical motility and survival. Moreover, 21.7% of IVM-treated hamsters developed lesions after being fed upon by infected sand flies. L. major promastigotes appeared to be tolerant to ng/mL blood levels of IVM that caused significant mortality for up to 10 days posttreatment in blood-feeding P. papatasi.