Altered distribution of juxtaparanodal kv1.2 subunits mediates peripheral nerve hyperexcitability in type 2 diabetes mellitus.

Peripheral nerve hyperexcitability (PNH) is one of the distal peripheral neuropathy phenotypes often present in patients affected by type 2 diabetes mellitus (T2DM). Through in vivo and ex vivo electrophysiological recordings in db/db mice, a model of T2DM, we observed that, in addition to reduced nerve conduction velocity, db/db mice also develop PNH. By using pharmacological inhibitors, we demonstrated that the PNH is mediated by the decreased activity of K(v)1-channels. In agreement with these data, we observed that the diabetic condition led to a reduced presence of the K(v)1.2-subunits in juxtaparanodal regions of peripheral nerves in db/db mice and in nerve biopsies from T2DM patients. Together, these observations indicate that the T2DM condition leads to potassium channel-mediated PNH, thus identifying them as a potential drug target to treat some of the DPN related symptoms.

HIV behavioural surveillance in Switzerland: trends in drug consumption, injection and syringe distribution, 1993-2011

Background: As part of the second generation surveillance system for HIV/Aids in Switzerland, repeated cross-sectional surveys were conducted in 1993, 1994, 1996, 2000, 2006 and 2011 among attenders of all low threshold facilities (LTFs) with needle exchange programmes and/or supervised drug consumption rooms for injection or inhalation. The number of syringes distributed to the injectors has also been measured annually since 2000. Distribution in other settings, such as pharmacies, is also monitored nationally. Methods: Periodic surveys of LTFs have been conducted using an interviewer/self-administered questionnaire structured along four themes: socio-demographic characteristics, drug consumption, risk/preventive behaviour and health. Analysis is restricted to attenders who had injected drugs during their lifetime (IDU´s). Pearson's chi-square test and trend analysis were conducted on annual aggregated data. Trend significance was assessed using Stata's non parametric test nptrend. Results: Median age of IDU´s increased from 26 years in 1993 to 40 in 2011; most are men (78%). Total yearly number of syringes distributed by LTFs has decreased by 44% in 10 years. Use of cocaine has increased (Table 1). Injection, regular use of heroin and borrowing of syringes/needles have decreased, while sharing of other material remains stable. There are fewer new injectors; more IDU´s report substitution treatment. Most attenders had ever been tested for HIV (90% in 1993, 94% in 2011). Reported prevalence of HIV remained stable around 10%; that of HCV decreased from 62% in 2000 to 42% in 2011. Conclusions: Overall, findings indicate a decrease in injection as a means of drug consumption in that population. This interpretation is supported by data from other sources, such as a national decrease in distribution from other delivery points. Switzerland's behavioural surveillance system is sustainable and allows the HIV epidemic to be monitored among this hard-to-reach population, providing information for planning and evaluation.

Comparison of copper-67- and iodine-125-labeled anti-CEA monoclonal antibody biodistribution in patients with colorectal tumors.

Copper-67 has comparable beta-particle emissions to that of 131I, but it displays more favorable gamma emission characteristics for application in radioimmunotherapy (RIT). This study investigates the potential of 67Cu-labeled monoclonal antibody (MAb) 35 for RIT of colorectal carcinoma. METHODS: Biokinetics of simultaneously injected 67Cu- and 125I-labeled MAb35 were studied in six patients scheduled for surgery of primary colorectal cancer. RESULTS: Whole-body clearance (T 1/2) of 67Cu, estimated from sequential anterior and posterior whole-body scans and corrected for decay of 67Cu, was 41 hr. Serum clearance of 67Cu was faster (27.41 hr) than that of 125I (38.33 hr). Mean tumor uptake of the 67Cu-labeled compound (0.0133% ID/g) exceeded that of 125I (0.0095% ID/g), and tumor-to-blood ratios were higher for 67Cu than for 125I, with averages of 6.07 and 2.41, respectively. The average 67Cu/125I ratio was 1.9 for tumor uptake, 0.7 for blood and 2.6 for tumor-to-blood ratios. Nonspecific liver uptake of 67Cu as calculated from whole-body scans was high in four patients, up to 25% of residual whole-body activity at 48 hr, but did not increase with time. We also observed some nonspecific bowel activity, as well as moderate to high uptake in benign polyps. CONCLUSION: Copper-67-labeled MAb35 is more favorable than its radioiodine-labeled counterpart for RIT of colorectal carcinoma due to higher tumor-to-blood ratios, but the problem of nonspecific liver and bowel uptake must first be overcome. The absolute accumulation of activity in tumor remains low, however, so the probability of cure with this compound alone is questionable. The use of 67Cu as one component of a multimodality adjuvant treatment seems to remain the most appropriate application for RIT.

Spatial distribution of schistosomiasis foci on Itamaracá Island, Pernambuco, Brazil

Acute cases of schistosomiasis have been found on the coastal area of Pernambuco, Brazil, due to environmental disturbances and disorderly occupation of the urban areas. This study identifies and spatially marks the main foci of the snail host species, Biomphalaria glabrata on Itamaracá Island. The chaotic occupation of the beach resorts has favoured the emergence of transmission foci, thus exposing residents and tourists to the risk of infection. A database covering five years of epidemiological investigation on snails infected by Schistosoma mansoni in the island was produced with information from the geographic positioning of the foci, number of snails collected, number of snails tested positive, and their infection rate. The spatial position of the foci were recorded through the Global Positioning System (GPS), and the geographical coordinates were imported by AutoCad. The software packages ArcView and Spring were used for data processing and spatial analysis. AutoCad 2000 was used to plot the pairs of coordinates obtained from GPS. Between 1998 and 2002 5009 snails, of which 12.2% were positive for S. mansoni, were collected in Forte Beach. A total of 27 foci and areas of environmental risk were identified and spatially analyzed allowing the identification of the areas exposed to varying degrees of risk.

Distribution and pathogenicity of Trypanosoma cruzi isolated from peridomestic populations of Triatoma infestans and Triatoma guasayana from rural Western Argentina

We assessed the distribution of Trypanosoma cruzi infection in peridomestic triatomines collected manually at a district-wide scale in rural villages around Olta, Western Argentina, and typed the isolated strains according to their pathogenicity to laboratory mice. Of 1623 triatomines examined, only 14 (0.9%) were infected with T. cruzi based on microscopical examination of feces. The prevalence of T. cruzi infection was 0.8% in Triatoma infestans, 2.3% in T. guasayana, and nil in T. garciabesi, T. platensis, and T. eratyrusiformis. Local transmission occurred in kitchens, store-rooms and goat corrals or nearby, though at very low levels. T. cruzi was detected by at least one parasitological method in 11 (79%) of 14 microscope-positive bugs. Hemoculture was the most sensitive method (67%) followed by culture of organ homogenates, histopathology or xenodiagnosis of inoculated suckling mice (55-58%), and culture of microscope-positive bug feces (46%). The evidence suggests that most of the isolated T. cruzi strains would be myotropic type III. Our study establishes for the first time that peridomestic, microscope-positive T. guasayana nymphs were actually infected with T. cruzi, and may be implicated as a putative secondary vector of T. cruzi in domestic or peridomestic sites.

Cytostatic lung perfusion results in heterogeneous spatial regional blood flow and drug distribution: evaluation of different cytostatic lung perfusion techniques in a porcine model.

OBJECTIVES: Comparison of doxorubicin uptake, leakage and spatial regional blood flow, and drug distribution was made for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), as opposed to intravenous administration in a porcine model. METHODS: White pigs underwent single-pass lung perfusion with doxorubicin (320 mug/mL), labeled 99mTc-microspheres, and Indian ink. Visual assessment of the ink distribution and perfusion scintigraphy of the perfused lung was performed. 99mTc activity and doxorubicin levels were measured by gamma counting and high-performance liquid chromatography on 15 tissue samples from each perfused lung at predetermined localizations. RESULTS: Overall doxorubicin uptake in the perfused lung was significantly higher (P = .001) and the plasma concentration was significantly lower (P < .0001) after all isolated lung perfusion techniques, compared with intravenous administration, without differences between them. Pulmonary artery infusion (blood flow occlusion) showed an equally high doxorubicin uptake in the perfused lung but a higher systemic leakage than surgical isolated lung perfusion (P < .0001). The geometric coefficients of variation of the doxorubicin lung tissue levels were 175%, 279%, 226%, and 151% for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), respectively, compared with 51% for intravenous administration (P = .09). 99mTc activity measurements of the samples paralleled the doxorubicin level measurements, indicating a trend to a more heterogeneous spatial regional blood flow and drug distribution after isolated lung perfusion and blood flow occlusion compared with intravenous administration. CONCLUSIONS: Cytostatic lung perfusion results in a high overall doxorubicin uptake, which is, however, heterogeneously distributed within the perfused lung.

Red cell distribution width does not predict stroke severity or functional outcome.

INTRODUCTION: Red cell distribution width was recently identified as a predictor of cardiovascular and all-cause mortality in patients with previous stroke. Red cell distribution width is also higher in patients with stroke compared with those without. However, there are no data on the association of red cell distribution width, assessed during the acute phase of ischemic stroke, with stroke severity and functional outcome. In the present study, we sought to investigate this relationship and ascertain the main determinants of red cell distribution width in this population. METHODS: We used data from the Acute Stroke Registry and Analysis of Lausanne for patients between January 2003 and December 2008. Red cell distribution width was generated at admission by the Sysmex XE-2100 automated cell counter from ethylene diamine tetraacetic acid blood samples stored at room temperature until measurement. An χ(2) -test was performed to compare frequencies of categorical variables between different red cell distribution width quartiles, and one-way analysis of variance for continuous variables. The effect of red cell distribution width on severity and functional outcome was investigated in univariate and multivariate robust regression analysis. Level of significance was set at 95%. RESULTS: There were 1504 patients (72±15·76 years, 43·9% females) included in the analysis. Red cell distribution width was significantly associated to NIHSS (β-value=0·24, P=0·01) and functional outcome (odds ratio=10·73 for poor outcome, P<0·001) at univariate analysis but not multivariate. Prehospital Rankin score (β=0·19, P<0·001), serum creatinine (β=0·008, P<0·001), hemoglobin (β=-0·009, P<0·001), mean platelet volume (β=0·09, P<0·05), age (β=0·02, P<0·001), low ejection fraction (β=0·66, P<0·001) and antihypertensive treatment (β=0·32, P<0·001) were independent determinants of red cell distribution width. CONCLUSIONS: Red cell distribution width, assessed during the early phase of acute ischemic stroke, does not predict severity or functional outcome.

Distribution and ecological aspects of Rhodnius pallescens in Costa Rica and Nicaragua and their epidemiological implications

In light of the Central American Initiative for the control of Chagas disease, efforts were made on the part of Costa Rican and Nicaraguan teams, working separately, to determine the present status of Rhodnius pallescens in areas close to the common border of the two countries, where the insect has appeared within the last few years. The opportunity was also used to establish whether R. prolixus, a vector present in some areas of Nicaragua, has been introduced in recent years into Costa Rica with Nicaraguan immigrants. It became evident that wild adults of R. pallescens are common visitors to houses in different towns of a wide area characterized as a humid, warm lowland, on both sides of the frontier. Up to the present, this bug has been able to colonize a small proportion of human dwellings only on the Nicaraguan side. There was strong evidence that the visitation of the adult bug to houses is related to the attraction of this species to electric lights. There were no indications of the presence of R. prolixus either in Nicaragua or in Costa Rica in this area of the Caribbean basin. Triatoma dimidiata, a widespread domestic species in both countries, was totally absent in the explored areas of Costa Rica but occasionally occurs on the Nicaraguan side. Serological surveys in children of both areas showed that transmission of Chagas disease takes place in a rather small degree in Costa Rica and more commonly in Nicaragua, indicating that R. pallescens could be a potential threat as a vector in this particular region.

Phlebotominae spatial distribution asssociated with a focus of tegumentary leishmaniasis in Las Lomitas, Formosa, Argentina, 2002

Las Lomitas, Formosa, Argentina, reported 96 cases of tegumentary leishmaniasis during 2002. The urban transmission was suggested although previous outbreaks were related with floods of the Bermejo river (BR) 50 km from the village. Phlebotomine collections were performed during March 2002 to define the spatial distribution of risk, together with satellite imaginery. The phlebotomine/trap obtained was 1679.5 in the southern BR shore, 1.1 in the periruban-rural environment and 2.3 in the northern Pilcomayo river marshes. Lutzomyia neivai was the prevalent species (91.1%) among the 2393 phlebotomine captured, and it was only found in the BR traps. The other species were L. migonei (7.9%), L. cortelezzii (0.9%), and Brumptomyia guimaraesi (0.1%). The satellite images analysis indicates that the fishing spots at the BR were significantlyoverflowed during the transmission peak, consistent with fishermen recollections. This spatial restricted flood might concentrate vectors, reservoirs, and humans in high places. Therefore, both the spatial distribution of vectors and the sensor remoting data suggests that in Las Lomitas area the higher transmission risk it is still related with the gallery forest of the BR, despite of the urban residence of the cases. The surveillance and control implications of these results are discussed.

Chagas disease in Mexico: an analysis of geographical distribution during the past 76 years - A review

Literature from 1928 through 2004 was compiled from different document sources published in Mexico or elsewhere. From these 907 publications, we found 19 different topics of Chagas disease study in Mexico. The publications were arranged by decade and also by state. This information was used to construct maps describing the distribution of Chagas disease according to different criteria: the disease, vectors, reservoirs, and strains. One of the major problems confronting study of this zoonotic disease is the great biodiversity of the vector species; there are 30 different species, with at least 10 playing a major role in human infection. The high variability of climates and biogeographic regions further complicate study and understanding of the dynamics of this disease in each region of the country. We used a desktop Genetic Algorithm for Rule-Set Prediction procedure to provide ecological models of organism niches, offering improved flexibility for choosing predictive environmental and ecological data. This approach may help to identify regions at risk of disease, plan vector-control programs, and explore parasitic reservoir association. With this collected information, we have constructed a data base: CHAGMEX, available online in html format.

Temporal distribution of dengue virus serotypes in Colombian endemic area and dengue incidence: re-introduction of dengue-3 associated to mild febrile illness and primary infection

We have investigated the temporal distribution of dengue (DEN) virus serotypes in the department (state) of Santander, Colombia, in relation to dengue incidence, infection pattern, and severity of disease. Viral isolation was attended on a total of 1452 acute serum samples collected each week from 1998 to 2004. The infection pattern was evaluated in 596 laboratory-positive dengue cases using an IgG ELISA, and PRNT test. The dengue incidence was documented by the local health authority. Predominance of DEN-1 in 1998 and DEN-3 re-introduction and predominance in 2001-2003 coincided with outbreaks. Predominance of DEN-2 in 2000-2001 coincided with more dengue hemorrhagic fever (DHF). DEN-4 was isolated in 2000-2001 and 2004 but was not predominant. There was an annual increase of primary dengue infections (from 13.7 to 81.4%) that correlated with frequency of DEN-3 (r = 0.83; P = 0.038). From the total number of primary dengue infections DEN-3 (81.3%) was the most frequent serotype. DHF was more frequent in DEN-2 infected patients than in DEN-3 infected patients: 27.5 vs 10.9% (P < 0.05). DEN-3 viruses belonged to subtype C (restriction site-specific-polymerase chain reaction) like viruses isolated in Sri-Lanka and other countries in the Americas. Our findings show the importance of continuous virological surveillance to identify the risk factors of dengue epidemics and severity.

The spatial distribution of Schistosoma mansoni infection before and after chemotherapy in the Jequitinhonha Valley in Brazil

Schistosomiasis prevalence and egg counts remained low one year after chemotherapy in most households in a hyperendemic rural area in northern Minas Gerais but several distinct spatial patterns could be observed in relation to IgE levels and to a lesser extent to exposure risk (TBM) and type of water supply. An inverse relationship between pre-treatment household prevalence and egg counts on the one hand and post-treatment IgE levels on the other were noted in two of the five communities. Low exposure risk was associated with the low pre-treatment infection rates in the central village but did not contribute to the decline of infection rates after chemotherapy in the study area, as indicated by the significant increase in water contact during the posttreatment period (p < 0.0001). Distance between households and the streams and socioeconomic factors were also unimportant in predicting the spatial distribution of infection. These results are consistent with the production and antiparasitic effect of high levels of IgE in Schistosoma mansoni infection.

Lutzomyia (Nyssomyia) whitmani s.l . (Antunes & Coutinho, 1939)(Diptera: Psychodidae: Phlebotominae): geographical distribution and the epidemiology of American cutaneous leishmaniasis in Brazil Mini-review

The aim of the present study, in view of the widespread geographical distribution of Lutzomyia (Nyssomyia) whitmani s.l. in Brazil, in close association with the regions of transmission of Leishmania (Viannia) braziliensis and L. (V.) shawi, is to investigate the distribution of this sand fly species and American cutaneous leishmaniasis (ACL) in relationship to vegetation and landscape ecology throughout Brazil. Thematic maps were elaborated by the MapInfo programme, giving information on the spatial distribution of L. whitmani s.l., in accordance with types of vegetation and foci of ACL. With regards to the known areas of transmission of ACL in Brazil, it is notable that L. (N.) whitmani s.l. occurs in most of them, where it has been implicated as a possible vector of L. (V.) braziliensis. The presence of L. whitmani s.l. has been registered in 26 states, the one exception being Santa Catarina; in some states such as Roraima, Acre, Tocantins, and Mato Grosso do Sul this sand fly species has been recorded in a large number of municipalities. L. whitmani s.l. has been found in association with a variety of vegetation types, including the Amazonian forest, savanna ("campos cerrados"), and northeastern savanna ("caatingas nordestinas" or "savana estépica").

Detection of Onchocerca volvulus (Nematoda: Onchocercidae) infection in vectors from Amazonian Brazil following mass Mectizan™ distribution

Detection of Onchocerca volvulus in Simulium populations is of primary importance in the assessment of the effectiveness of onchocerciasis control programs. In Brazil, the main focus of onchocerciasis is in the Amazon region, in a Yanomami reserve. The main onchocerciasis control strategy in Brazil is the semi-annually mass distribution of the microfilaricide ivermectin. In accordance with the control strategy for the disease, polymerase chain reaction (PCR) was applied in pools of simuliids from the area to detect the helminth infection in the vectors, as recommended by the Onchocerciasis Elimination Program for the Americas and the World Health Organization. Systematic sampling was performed monthly from September 1998 to October 1999, and a total of 4942 blackflies were collected from two sites (2576 from Balawaú and 2366 from Toototobi). The molecular methodology was found to be highly sensitive and specific for the detection of infected and/or infective blackflies in pools of 50 blackflies. The results from the material collected under field conditions showed that after the sixth cycle of distribution of ivermectin, the prevalence of infected blackflies with O. volvulus had decreased from 8.6 to 0.3% in Balawaú and from 4 to 0.1% in Toototobi.

Nyssomyia intermedia (Lutz & Neiva, 1912) and Nyssomyia neivai (Pinto, 1926) (Diptera: Psychodidae: Phlebotominae) geographical distribution and epidemiological importance

Nyssomyia intermedia (Lutz & Neiva 1912) and N. neivai (Pinto 1926) are possible vectors of tegumentary leishmaniasis in some regions of Brazil. Further, the latter was until recently, considered a junior synonym of the former. This study has the purpose of updating our knowledge of the geographical distribution of these species, based on specimens deposited at the collection of the Centro de Pesquisas René Rachou-Fiocruz, Faculdade de Saúde Pública-Universidade de São Paulo, and on data presented by literature as also to associate this distribution with the cutaneous leishmaniasis cases reported. It has been reported that N. intermedia occurs in the states of the Northeastern Region, in Rio de Janeiro, Espírito Santo, on the northern coast of São Paulo, in eastern Minas Gerais, Mato Grosso do Sul, and Goiás, close to the border with Minas Gerais and Bahia. N. neivai occurs in the Southern Region, southern coast and in western São Paulo, southern and western Minas Gerais, southern Goiás, and southern Pará, beyond Argentina, Bolivia, and Paraguay. It is important to highlight that N. intermedia and N. neivai occur in sympatry in Minas Gerais and São Paulo. N. intermedia or N. neivai are predominant or are captured abundantly in several cutaneous leishmaniasis foci in the Southeastern and Southern regions of Brazil.