Paclitaxel Regulates TRPA1 Function and Expression Through PKA and PKC.

Paclitaxel (PTX) is a frequently used anticancer drug that causes peripheral neuropathy. Transient receptor potential ankyrin 1 (TRPA1), a plasma membrane calcium channel, has been associated with PTX toxicity and with other chemotherapy agents such as oxaliplatin and vincristine. However, the effect of PTX on the functional expression and calcium currents of TRPA1 has not been determined. The present study shows the effect of PTX on TRPA1 activity in a neuronal cell line (SH-SY5Y). The effect of PTX on the expression of TRPA1 was assessed through quantitative PCR and Western blot analyses to determine the relative mRNA and protein expression levels. To assess the effect on calcium flux and currents, cells were exposed to PTX; simultaneously, a specific agonist and antagonist of TRPA1 were added to evaluate the differential response in exposed versus control cells. To assess the effect of PKA, PKC and PI3K on PTX-induced TRPA1 increased activity, selective inhibitors were added to these previous experiments. PTX increased the mRNA and protein expression of TRPA1 as well as the TRPA1-mediated Ca2+ currents and intracellular Ca2+ concentrations. This effect was dependent on AITC (a selective specific agonist) and was abolished with HC-030031 (a selective specific antagonist). The inhibition of PKA and PKC reduced the effect of PTX on the functional expression of TRPA1, whereas the inhibition of PI3K had no effects. PTX-induced neuropathy involves TRPA1 activity through an increase in functional expression and is regulated by PKA and PKC signaling. These findings support the role of the TRPA1 channel in the mechanisms altered by PTX, which can be involved in the process that lead to chemotherapy-induced neuropathy.

Spatial distribution of Zika virus infection in Northeastern Colombia.

In this study, we investigated the weekly reported spatio-temporal distribution and topographic risk factors for Zika virus (ZIKV) infection in northeastern Colombia. Weekly reported surveillance data, including clinical, suspected and confirmed cases from the ongoing ZIKV epidemic in the Santander and Norte de Santander departments (Santanderes) in Colombia were used to estimate cumulative incidence rates. Spatial analysis was performed to develop hot spot maps and to identify spatial topographic risk factors for infection. From January 1, 2016 to March 19, 2016, 11,515 cases of ZIKV were reported in Santanderes, with cumulative rates of 316.07 cases/100,000 population for the region (representing 18.5% of the cases of the country). Five municipalities (four in Norte de Santander) reported high incidence of ZIKV infection (>1,000 cases/100,000 pop); these municipalities are close to the border with Venezuela. Most of the cases reported occurred mainly in low altitude areas, and persistent hot spots were observed. Higher infection rates were reported in the Northeastern part of the study area. Use of risk maps can help guide decisions for the prevention and control of ZIKV. Hotspots on the Colombia-Venezuela border can have implications for international spread.

Mapping the ecoepidemiology of Zika virus infection in urban and rural areas of Pereira, Risaralda, Colombia, 2015-2016: Implications for public health and travel medicine.

OBJECTIVE: Geographical information systems (GIS) have been demonstrated earlier to be of great use to inform public health action against vector-borne infectious diseases. METHODS: Using surveillance data on the ongoing ZIKV outbreak from Pereira, Colombia (2015-2016), we estimated incidence rates (cases/100,000 population), and developed maps correlating with the ecoepidemiology of the area. RESULTS: Up to October 8, 2016, 439 cases of ZIKV were reported in Pereira (93 cases/100,000 pop.), with highest rates in the South-West area. At the corregiments (sub-municipalities) of Pereira, Caimalito presented the highest rate. An urban area, Cuba, has 169 cases/100,000 pop., with a low economical level and the highest Aedic index (9.1%). Entomological indexes were associated with ZIKV incidence at simple and multiple non-linear regressions (r2 > 0.25; p < 0.05). CONCLUSIONS: Combining entomological, environmental, human population density, travel patterns and case data of vector-borne infections, such as ZIKV, leads to a valuable tool that can be used to pinpoint hotspots also for infections such as dengue, chikungunya and malaria. Such a tool is key to planning mosquito control and the prevention of mosquito-borne diseases in local populations. Such data also enable microepidemiology and the prediction of risk for travelers who visit specific areas in a destination country.

Mapping Zika virus disease incidence in Valle del Cauca.

OBJECTIVE: Geographical information systems (GIS) use for development of epidemiological maps in tropical diseases is increasingly frequently utilized. Here, we apply this technique to map the current Zika virus (ZIKV) outbreak in Colombia. METHODS: Surveillance cases data of the ongoing epidemic of ZIKV in Valle del Cauca department and its capital, Cali (2015-2016), were used to estimate cumulated incidence rates (cases/100,000 population) to develop the first maps in the department and it municipalities. The GIS software used was Kosmo Desktop 3.0RC1®. Three thematic incidence rate maps were developed. RESULTS: Up to April 2, 2016, 9,825 cases of ZIKV were reported (15.15 % of the country cases). The burden of ZIKV infection has been concentrated in the North of the department. Valle del Cauca borders with other departments with incidence of ZIKV infection, such as Quindío (173 cases) and Risaralda (687 cases). Eleven municipalities of Valle del Cauca had cases in the range between 250 and 499 cases/100,000, all in the North and East of the department. Cali, the capital concentrates more than a third of the reported cases of ZIKV in Valle del Cauca. CONCLUSIONS: Use of GIS-based epidemiological maps allows to guide decision-making for prevention and control of diseases that constitute significant public health problems in the region and the country, such as exemplified by the emergence of ZIKV infection, particularly in departments such as Valle del Cauca with a high disease incidence.

Mapping Zika virus infection using geographical information systems in Tolima, Colombia, 2015-2016.

OBJECTIVE: Geographical information systems (GIS) have been extensively used for the development of epidemiological maps of tropical diseases, however not yet specifically for Zika virus (ZIKV) infection. METHODS: Surveillance case data of the ongoing epidemics of ZIKV in the Tolima department, Colombia (2015-2016) were used to estimate cumulative incidence rates (cases/100,000 pop.) to develop the first maps in the department and its municipalities, including detail for the capital, Ibagué. The GIS software used was Kosmo Desktop 3.0RC1®. Two thematic maps were developed according to municipality and communes incidence rates. RESULTS: Up to March 5, 2016, 4,094 cases of ZIKV were reported in Tolima, for cumulated rates of 289.9 cases/100,000 pop. (7.95% of the country). Burden of ZIKV infection has been concentrated in its east area, where municipalities have reported >500 cases/100,000 pop. These municipalities are bordered by two other departments, Cundinamarca (3,778 cases) and Huila (5,338 cases), which also have high incidences of ZIKV infection. Seven municipalities of Tolima ranged from 250-499.99 cases/100,000 pop., of this group five border with high incidence municipalities (>250), including the capital, where almost half of the reported cases of ZIKV in Tolima are concentrated. CONCLUSIONS: Use of GIS-based epidemiological maps helps to  guide decisions for the prevention and control of diseases that represent significant issues in the region and the country, but also in emerging conditions such as ZIKV.