Ignacio García-Alonso

A micromachined pressure sensor for biomedical applications

A silicon pressure microsensor fabrication process is reported. The microsensor has been designed as a low-cost disposable device for invasive blood pressure measurements. Results obtained from static, dynamic and leakage pressure tests are presented. A sensitivity of has been measured. The combined linearity and hysteresis is less than 1.5% FSO. The dynamic response is fast enough to reproduce the blood pressure waveform of the human heart. Results based on a material biocompatibility study are also included.

Effect of allopurinol, folinic acid, SOD and cyclosporine A on ischemic liver regeneration.

Liver regeneration plays a key role in restoring the liver/body ratio after partial liver transplantation. However, hepatic ischemia hinders the proliferative response of the hepatocytes. In this study, different ways of improving the regenerating capacity of ischemic hepatocytes are tested. Following 70% hepatectomy and 15 min of normothermic liver ischemia, the percentage of regenerating hepatocytes and the regenerative gradient are assessed. Cyclosporine A (hepatotrophic agent), superoxide dismutase and folinic acid (antioxidants), administered during the ischemic period, have significantly increased these indices. The later drug has restored the regenerative response to the levels of normoperfused livers.

The Effect of Knee Flexion Angle on the Neurovascular Safety of All-Inside Lateral Meniscus Repair: A Cadaveric Study

PURPOSE To evaluate if different knee flexion angles can modify the neurovascular injury risk during lateral meniscus repair. METHODS Twenty cadaveric knees were studied. An all-inside suture device (FasT-Fix; Smith & Nephew, Andover, MA) was placed at the posterior horn and at the medial and lateral limits of the popliteal hiatus. The minimal distances between the device and the popliteal artery and peroneal nerve were measured with the knee at 90°, 45°, and 0° of flexion through a limited posterolateral arthrotomy. RESULTS The distance between the device when inserted at the lateral edge of the popliteal hiatus and the peroneal nerve decreased from a median of 26 mm (interquartile range [IQR], 3.5 mm; range, 19 to 29 mm) at 90° to 21.5 mm (IQR, 4.5 mm; range, 14 to 25 mm) at 45° and 15.5 mm (IQR, 6.5 mm; range, 4 to 20 mm) at 0° (significant differences, P < .001). The distance between the device when inserted at the medial edge of the popliteal hiatus and the peroneal nerve decreased from 16 mm (IQR, 3.3 mm; range, 9 to 21 mm) at 90° to 12 mm (IQR, 4.3 mm; range, 9 to 16 mm) at 45° and 7 mm (IQR, 4.0; range, 4 to 15 mm) at 0° (significant differences, P < .001). The distance between the device when inserted at the medial edge of the popliteal hiatus and the popliteal artery decreased from 21 mm (IQR, 5.0 mm; range, 11 to 27 mm) at 90° to 19 mm (IQR, 5.0 mm; range, 10 to 23 mm) at 45° and 16 mm (IQR, 7.5 mm; range, 10 to 23 mm) at 0° (significant differences, P < .001). The distance between the device when inserted 5 mm lateral to the posterior root of the lateral meniscus and the popliteal artery decreased from 13 mm (IQR, 4.3 mm; range, 7 to 27 mm) at 90° to 10.5 mm (IQR, 4.3 mm; range, 4 to 19 mm) at 45° and 5.5 mm (IQR, 4.0 mm; range, 0 to 14 mm) at 0° (significant differences, P < .001). CONCLUSIONS The risk of injury to the popliteal artery or to the peroneal nerve during all-inside repair of the posterior half of the lateral meniscus is lower at 90° of flexion and increases with knee extension to 45° and 0°. CLINICAL RELEVANCE All-inside meniscal repair of the lateral meniscus is safer with the knee at 90° of flexion.

Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy

Magnetic nanoparticle (MNP)-mediated hyperthermia (MH) coupled with radiation therapy (RT) is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application of the two treatment techniques. These recommendations were developed by the members of Working Group 3 of COST Action TD 1402: Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (“Radiomag”). The purpose of the recommendations is not to provide definitive answers and directions but, rather, to outline those tests and considerations that a researcher must address in order to perform in vitro and in vivo studies. The recommendations are divided into 5 parts: (a) in vitro evaluation of MNPs; (b) in vitro evaluation of MNP-cell interactions; (c) in vivo evaluation of the MNPs; (d) MH combined with RT; and (e) pharmacokinetic studies of MNPs. Synthesis and characterization of the MNPs, as well as RT protocols, are beyond the scope of this work.

Growth Factors and the Redox State as New Therapeutic Targets for Colorectal Cancer

Colorectal cancer (CRC) is an important health problem in many western countries due to its significant morbidity/mortality. Despite advances in its diagnosis and treatment, survival associated with this cancer when it has extended to adjacent organs, lymphatic nodules or distal organs is drastically reduced. The liver is the most common site of CRC metastasis, since it represents a unique microenvironment for the formation of metastases, not only due to its sinusoidal endothelium (Barbera-Guillen et al., 1989), but also due to its abundant expression of growth factors (GFs) (Stoeltzing et al., 2003). At present, curative treatment of localized metastases is possible via partial liver resection. However, this surgical procedure is only potentially curative, since 65% of patients subjected to resection of liver metastases experience relapse within 5 years (Sun & Tang, 2003; Allendorf et al., 2004). In the light of this frequent recurrence, it is essential to develop new preventive therapeutic strategies, which require a detailed knowledge of the biological events that occur following hepatectomy. In this sense, we have previously demonstrated the tumor-enhancing effect associated with liver resection in a mouse tumor model; in addition, we showed that hepatectomized rat serum increased cell proliferation in vitro, when compared with laparotomized rat serum or fetal calf serum (Garcia-Alonso et al., 2003; Garcia-Alonso et al., 2008a, 2008b). These findings indicated that GFs produced by the liver promote the development of metastases. At present, CRC treatment includes various active drugs, either as individual agents or in combination: 5-fluorouracil (5-FU), capecitabine, irinotecan and oxaliplatin, among others. Despite this wide array of anti-tumor agents, relapse often occurs in CRC patients, due in large part to the resistance of the tumor cells to these anti-neoplastic agents. Various different mechanisms have been reported as being responsible for the development of chemoresistance and, though each may be important in itself, they take on an even greater significance if we consider how they may be interrelated. One of these mechanisms of resistance to anti-neoplastic agents is the presence of GFs, which may be able to protect certain tumor cells against cytotoxic cell death. For this reason, one of the most promising cell targets nowadays are these GFs and their receptors. Thus, since 2004, three new agents have been approved which in combination with cytotoxic

El flujo como indicador del efecto terapéutico del ácido folínico en la isquemia-reperfusión

Objective: an intestinal reperfusion study with two aims: a) to assess the usefulness of intestinal capillary blood flow measurement by laser-Doppler for intestinal reperfusion studies; and b) to compare the effects of racemic and levo forms of folinic acid in treating the syndrome. Experimental design: a murine model of intestinal ischemia by completely clamping the superior mesenteric artery for 90 minutes. A comparison was made of three treatment groups: saline, folinic acid, and levo-folinic acid. The following factors were analyzed: changes in biochemical parameters (levels of creatine kinase, lactic dehydrogenase, and alkaline phosphatase at 60 minutes, and at two and seven days after restoring blood flow), capillary flow in the jejunum and ileum by laser-Doppler (during ischemia and after the first hour of reperfusion), intestinal mucosa injury, and survival curve. Results: laser-Doppler provided reliable data on how the different treatments affected capillary flow during intestinal reperfusion. Levo-folinic acid improved capillary flow in the ileum after 25 minutes of reperfusion, and also reduced mucosal injury in the same stretch of intestine by the seventh day post-reperfusion (p < 0.05). On the other hand, it produced an initial increase in serum enzymes during reperfusion, and did not modify survival. Conclusions: the changes observed in intestinal capillary blood flow measurement by laser-Doppler have similarities with the effects of drugs on pathological mucosal changes. We could not prove that the levo form of folinic acid has a stronger protective effect versus racemic folinic acid in intestinal ischemia-reperfusion syndrome.