Evaluation of the Surgical Pleth Index (SPI) for the monitoring of the nociception-antinociception balance in dogs undergoing castration: A prospective clinical trial.

The aim of this prospective clinical study was to evaluate the efficacy of the Surgical Pleth Index (SPI), a validated nociception monitor in human anaesthesia, in dogs. The technology uses a plethysmographic signal from a specific pulse oximetry probe to analyse pulse wave amplitudes and heartbeat intervals. Twenty-six healthy dogs anaesthetised for castration were included. SPI, invasive mean arterial pressure (MAP) and heart rate (HR) were continuously monitored. The occurrence or resolution of a haemodynamic reaction (HDR), defined as a > 20% increase in HR and/or MAP, was assessed at predefined times: cutaneous incision, testicles' exteriorization, cutaneous suture, and fentanyl administration. Following nociceptive events, the dogs presenting a HDR showed a significant 8% and 10% increase in SPI at 3 and 5 min respectively, whereas after fentanyl administration, a 13% and 16% significant decrease in SPI were noted. Receiver operating characteristic curves analysis indicated a moderate performance for the dynamic variations of SPI over 1 min to predict a HDR (AUC: 0.68, threshold value: +15%) or its resolution after fentanyl administration (AUC of 0.72, threshold value: -15%) within 3 min. The SPI varied according to perioperative nociceptive events and analgesic treatment; however, its performance to anticipate a HDR was limited with high specificity but low sensivity. Refinement of the algorithm to specifically accommodate for the canine species may be warranted. Further studies are required to evaluate the influence of other factors on the performance of this index.

Evaluation of the nociception-antinociception balance using the Parasympathetic Tone Activity index in dogs anaesthetized for castration.

OBJECTIVE: To evaluate the performance of the Parasympathetic Tone Activity (PTA) index in assessing the nociception-antinociception balance in anaesthetized dogs undergoing castration. STUDY DESIGN: Prospective clinical study. ANIMALS: A group of 22 healthy client-owned dogs. METHODS: The dogs underwent general anaesthesia, with continuous monitoring of mean and instantaneous PTA (PTAm, PTAi), mean arterial pressure and heart rate. The values of these variables were divided according to the occurrence or absence of a haemodynamic reaction (HDR) at different time points: during surgical preparation, cutaneous incision, testicles extraction, cutaneous suture, after fentanyl administration, and after dexmedetomidine administration during recovery. Data were collected initially and 1, 3 and 5 minutes after each time point. The performance of the dynamic variation of the PTA (ΔPTA) to predict HDR or its resolution within 3 or 5 minutes was assessed using receiver operating characteristic (ROC) curves analysis. A p value < 0.05 was considered significant. RESULTS: During HDR, a decrease in PTAi (-34% and -31%) and PTAm (-26% and -30%) occurred at 3 (p = 0.005; p = 0.004) and 5 minutes (p = 0.001), respectively. After fentanyl administration, a decrease in haemodynamic variables occurred with a 45% increase in PTAi (p = 0.004). The ROC curve analysis of pooled data of the ΔPTAi for the prediction of HDR within 3 minutes indicated an area under the curve (AUC) of 0.70 (p = 0.0016) (threshold value: -16%). After fentanyl administration, the ROC curve analysis of ΔPTAi for the prediction of resolution of HDR within 3 minutes indicated an AUC of 0.69 (threshold value: +12%). CONCLUSIONS AND CLINICAL RELEVANCE: The PTAi appears to be an interesting tool to assess the nociception-antinociception balance. However, further studies with a variety of clinical scenarios and anaesthesia protocols are required to conclude on its performance.

Effects of chronic dietary nitrate supplementation on longevity, vascular function and cancer incidence in rats.

RATIONALE: Dietary nitrate and nitrite have a notoriously bad reputation because of their proposed association with disease, in particular cancer. However, more recent lines of research have challenged this dogma suggesting that intake of these anions also possess beneficial effects after in vivo conversion to the vital signaling molecule nitric oxide. Such effects include improvement in cardiovascular, renal and metabolic function, which is partly mediated via reduction of oxidative stress. A recent study even indicates that low dose of dietary nitrite extends life span in fruit flies. METHODS: In this study, 200 middle-aged Wistar rats of both sexes were supplemented with nitrate or placebo in the drinking water throughout their remaining life and we studied longevity, biochemical markers of disease, vascular reactivity along with careful determination of the cause of death. RESULTS: Dietary nitrate did not affect life span or the age-dependent changes in markers of oxidative stress, kidney and liver function, or lipid profile. Ex vivo examination of vascular function, however, showed improvements in endothelial function in rats treated with nitrate. Neoplasms were not more common in the nitrate group. CONCLUSION: We conclude that chronic treatment with dietary nitrate does not affect life span in rats nor does it increase the incidence of cancer. In contrast, vascular function was improved by nitrate, possibly suggesting an increase in health span.

Genetic mapping and phenotypic analysis of shotH.3.2 in Drosophila melanogaster.

Genetic screens are used to identify genes involved in specific biological processes. An EMS mutagenesis screen in Drosophila melanogaster identified growth control phenotypes in the developing eye. One mutant line from this screen, H.3.2, was phenotypically characterized using the FLP/FRT system and genetically mapped by complementation analysis and genomic sequencing by undergraduate students participating in the multi-institution Fly-CURE consortium. H.3.2 was found to have a nonsense mutation in short stop (shot), anortholog of the mammalian spectraplakin dystonin (DST). shot and DST are involved in cytoskeletal organization and play roles during cell growth and proliferation.

Biocompatibility of a HA/ß-TCP/C Scaffold as a Pulp-Capping Agent for Vital Pulp Treatment: An In Vivo Study in Rat Molars.

Bioceramic materials possess desirable biological properties, highlighting their non-reactivity and osteoconductivity. Their use has been extended in vital pulp treatment. The purpose of this study was to evaluate and compare the effects of beta-tricalcium phosphate (ß-TCP), hydroxyapatite (HA), and collagen (C) scaffold with mineral trioxide aggregate (MTA) on the vital pulp of rat molars. Thirty-two molars of Sprague-Dawley rats underwent direct pulp capping with ß-TCP/HA/C (n = 16) and MTA (n = 16). After 30 days, the following parameters were evaluated in the tested samples: the degree of pulp inflammation and pulp vitality, the presence of reparative dentin, the homogeneity of the odontoblastic layer, and the presence of pulp fibrosis. No statistically significant differences were observed between HA/ß-TCP/C and MTA in terms of the degree of inflammation (p = 0.124). Significant differences were found in reparative dentin formation between the treatment groups (p = 0.0005). Dentin bridge formation was observed in the MTA-treated group. The local action of HA/ß-TCP/C is similar to that of MTA when used as an agent for pulp vital treatment in terms of absence of inflammation and maintenance of pulp vitality, although there are significant differences between both materials regarding the formation of dentin bridges.

Coconut Oil Supplementation Does Not Affect Blood Pressure Variability and Oxidative Stress: A Placebo-Controlled Clinical Study in Stage-1 Hypertensive Patients.

Exploring an alternative to improve the clinical management of hypertension, we tested the hypothesis that food supplementation with coconut oil (EVCO), alone or combined with aerobic exercise training, could exert an antihypertensive effect (primary outcome) in patients with stage 1 hypertension. Forty-five hypertensive volunteers of both genders participated in a placebo-controlled clinical trial. The volunteers were submitted to 24-hour ambulatory blood pressure monitoring, analysis of blood pressure variability (BPV), measurement of serum malondialdehyde (MDA) and nutritional assessment. Results indicate that EVCO consumption had no adverse effects. The supplementation did not increase the caloric intake compared with placebo, and the dietary constituents were similar between groups, except for the saturated fats, especially lauric acid. The analysis of blood pressure indicated absence of antihypertensive effect of EVCO alone or combined with physical training. Furthermore, no effects on blood pressure variability and oxidative stress were observed in the supplemented hypertensive patients. Thus, despite the results observed in pre-clinical studies, the current clinical study did not provide evidence to support the use of coconut oil as an adjuvant in the management of hypertension in humans.

Melatonin as an Agent for Direct Pulp-Capping Treatment.

Melatonin plays an essential role in the regulation of bone growth. The actions that melatonin exerts on odontoblasts may be similar to its action on osteoblasts. This research aimed to evaluate the pulp response to melatonin used for direct pulp capping to evaluate the antioxidant effect of melatonin administered orally and its influence on dental pulp. Direct pulp capping was performed on the upper molars of Sprague Dawley rats using melatonin or Mineral Trioxide Aggregate (MTA). The study groups were: MTA; Melatonin; MTA + Melatonin administered orally; and Melatonin + Melatonin administered orally. In the latter two groups, the animals drank water dosed with melatonin ad libitum (10 mg/100 mL). After 30 days, the animals were sacrificed, and 5 ml of blood, the kidneys, and the liver were extracted in order to evaluate oxidative stress using thiobarbituric acid reactive substances testing (TBARS). Fragments of the maxilla containing the study molars were prepared for histological evaluation. The degree of pulp inflammation and pulp necrosis, the presence of reparative dentin and dentin bridging the pulp chamber, the presence and regularity of the odontoblastic layer, and the presence of pulp fibrosis were evaluated. No significant differences were found between the four study groups for any of the studied histological variables. The oral administration of melatonin did not modify the local effects of MTA or melatonin on dental pulp, or reduce basal-level oxidative stress. The effect of melatonin on pulp is similar to that of MTA and may be used as an agent for direct pulp capping.

Oleocanthal Inhibits Catabolic and Inflammatory Mediators in LPS-Activated Human Primary Osteoarthritis (OA) Chondrocytes Through MAPKs/NF-κB Pathways.

BACKGROUND/AIMS: Oleocanthal (OC), a phenolic compound present in extra virgin olive oil (EVOO), has attracted attention since its discovery for its relevant pharmacological properties in different pathogenic processes, including inflammation. Here, we investigated the involvement of OC in LPS-activated osteoarthritis (OA) human primary chondrocytes. METHODS: Human primary chondrocytes were harvested from articular cartilage samples obtained from OA patients. The effects of OC on the viability of chondrocytes were tested by MTT assay. Protein and mRNA expression of several catabolic and pro-inflammatory factors after OC treatment were measured by RT-qPCR and western blot respectively. Moreover, we analysed the NO production by Griess reaction. Finally, several pathways mediators were analysed by western blot. RESULTS: We demonstrated that OC did not have any cytotoxic effect. Oleocanthal inhibited NO production and strongly decreased NOS2 and COX-2 protein and mRNA expression in LPS-activated human primary OA chondrocytes. Interestingly, OC also inhibits MMP-13 and ADAMTS-5. In addition, OC downregulates several pro-inflammatory factors, such as IL-6, IL-8, CCL3, LCN2 and TNF-α induced by LPS in human primary OA chondrocytes. Finally, we demonstrated that OC exerts its effects through the MAPK/P38/NF-kB pathways. CONCLUSION: These data show that OC is able to block LPS-mediated inflammatory response and MMP-13 and ADAMTS-5 induction in human primary OA chondrocytes via MAPKs/NF-kB pathways, suggesting that OC may be a promising agent for the treatment of inflammation in cartilage and a potential molecule to prevent disease progression by inhibiting metalloproteases and aggrecanases.

Successful Cardiopulmonary Resuscitation in a Sevoflurane Anaesthetized Horse That Suffered Cardiac Arrest at Recovery.

A 17-year-old mare undergoing dental surgery suffered a cardiac arrest while being transferred from the surgical theatre to the recovery box. This complication was diagnosed early, thus allowing a prompt start to the cardiopulmonary resuscitation maneuvers. External thoracic compressions, intermittent positive pressure ventilation, and adrenaline administration were at the core of this successful resuscitation. Although it was not possible to confirm the cause of cardiac arrest in this horse, a Bezold-Jarisch reflex due to potential decrease on venous return because of postural change and drug interactions was hypothesized. Based on this report, it appears advisable to smoothly change the position of anaesthetized patient; furthermore, the administration of drugs affecting cardiovascular hemodynamics or sympatho-vagal balance to animals while changing their recumbency should be avoided.

Evaluation of the Parasympathetic Tone Activity (PTA) index to assess the analgesia/nociception balance in anaesthetised dogs.

The Parasympathetic Tone Activity (PTA) is an index based on the analysis of heart rate variability that has been recently developed to assess the analgesia/nociception balance in anaesthetised animals. The present study aimed to evaluate its performance in dogs undergoing surgery. Thirty dogs admitted for elective surgeries, were anaesthetised with a standardised protocol. PTA, heart rate (HR), systolic blood pressure (SBP) and HDR (defined as an increase by >20% in HR and/or SBP within 5min) were assessed at the following predefined time-points: TStSt (steady-state, after induction of anaesthesia and before start of surgery), TClamp (clamping of surgical drapes on the skin), TCut (cutaneous incision), TPrePTA (retrospectively assessed 1min before a PTA decline of at least 20%) and TEndIso (isoflurane discontinuation). The dynamic variation of PTA over 1min (∆PTA) was calculated at each predefined time-points and its performance to predict HDR was assessed by building Receiver Operating Characteristics (ROC) curves. A significant decrease of PTA (p<0.002) was detected 1min after TClamp, TCut and TPrePTA followed by a significant increase in HR and/or SBP within 5min after the time points (p<0.01). The ΔPTA was associated with the following performance in predicting HDR: AUC ROC [95% CI]=0.80 [0.71 to 0.88] (p<0.05), with a sensitivity of 77% and a specificity of 72% for a threshold value of -18%. Although encouraging, the performance of the PTA index and its dynamic variation needs to be further evaluated, particularly in different clinical contexts.

Alfaxalone for total intravenous anaesthesia in bitches undergoing elective caesarean section and its effects on puppies: a randomized clinical trial.

OBJECTIVE: To evaluate the effects and reliability of alfaxalone constant rate infusion (CRI) in comparison to isoflurane to maintain anaesthesia in bitches undergoing elective caesarean section. STUDY DESIGN: Prospective, randomized, 'blinded' clinical trial. ANIMALS: Twenty-two client-owned bitches and 94 puppies. METHODS: Bitches were randomly assigned to receive an alfaxalone CRI [0.2 mg kg(-1)  minute(-1) intravenously (IV), and once the last puppy was delivered, the dose was halved; n = 11] or 2% (vaporizer dial setting) isoflurane (n = 11) for maintenance of anaesthesia. All dogs were induced with alfaxalone (3 mg kg(-1) ) IV. Additional alfaxalone (0.3 mg kg(-1) IV) was administered if the depth of anaesthesia was inadequate and the total dose was calculated. Bitches were mechanically ventilated. Analgesia was administered after the delivery of puppies. Physiological variables were recorded every 5 minutes. The bitches' recovery times were also recorded. Quality of induction and recovery were evaluated. Puppies' vigour was evaluated with a modified Apgar score at 5 and 60 minutes after birth. Puppies' survival rates at 24 and 48 hours and at 15 days were recorded. Data were analysed using an anova, Student's t-test or Wilcoxon rank-sum test. RESULTS: The rescue dose of alfaxalone was higher (p = 0.01); bitches' recoveries were longer (p < 0.001) and puppies' Apgar scores were significantly lower at 5 and 60 minutes (p < 0.001 and p = 0.003, respectively) with alfaxalone than with isoflurane. However, no significant differences were found for puppies' survival between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone CRI seems to be a possible protocol for puppies and bitches undergoing elective caesarean sections. However, bitches recovered more slowly and puppy Apgar scores were lower in comparison to isoflurane.

Design of a beneficial product for newborn calves by combining Lactobacilli, minerals, and vitamins.

Diarrhea is one of the most frequent diseases affecting newborn calves in intensive systems. Several strategies were proposed to protect and improve health, such as probiotics. This work was directed to design a product containing freeze-dried bacteria, vitamins, and minerals, as well as to optimize conditions with lyoprotectors, combine strains and add vitamins, minerals, and inulin to the product. The lyoprotectors were milk, milk-whey, and actose, and products were stored for 6 months at 4°C. Combined bacteria were freeze-dried in milk and the final products were added with minerals, vitamins, and insulin. The viable cells were determined by the plate count assay and antibiotic profiles to differentiate strains. Lactobacillus johnsonii CRL1693, L. murinus CRL1695, L. mucosae CRL1696, L. salivarius CRL1702, L. amylovorus CRL1697, and Enterococcus faecium CRL1703 were evaluated. The optimal conditions were different for each strain. Milk and milk whey maintained the viability during the process and storage after 6 months for most of the strains, except for L. johnsonii. Lactose did not improve cell's recovery. L. murinus was viable for 6 months in all the conditions, with similar results in enterococci. In strains combined before freeze-dried, the viability decreased deeply, showing that one-step process with bacteria mixtures, vitamins, and minerals were not adequate. Freeze-dried resistance depends on each strain and must be lyophilized individually.

Effect of Pre- and Postoperative Phenylbutazone and Morphine Administration on the Breathing Response to Skin Incision, Recovery Quality, Behavior, and Cardiorespiratory Variables in Horses Undergoing Fetlock Arthroscopy: A Pilot Study.

This prospective blinded randomized study aimed to determine whether the timing of morphine and phenylbutazone administration affects the breathing response to skin incision, recovery quality, behavior, and cardiorespiratory variables in horses undergoing fetlock arthroscopy. Ten Standardbred horses were premedicated with acepromazine (0.04 mg kg(-1) IM) and romifidine (0.04 mg kg(-1) IV). Anesthesia was induced with diazepam (0.05 mg kg(-1)) and ketamine (2.2 mg kg(-1)) IV at T0. Horses in group PRE (n = 5) received morphine (0.1 mg kg(-1)) and phenylbutazone (2.2 mg kg(-1)) IV after induction and an equivalent amount of saline after surgery. Horses in group POST (n = 5) received the inversed treatment. Anesthesia was maintained with isoflurane 2% in 100% oxygen. Hypotension (mean arterial pressure <60 mmHg) was treated with dobutamine. All horses breathed spontaneously. Dobutamine requirements, respiratory rate (f R), heart rate (HR), mean arterial blood pressure, end-tidal CO2, inspired (i) and expired (e) tidal and minute volume (V T and [Formula: see text]), inspiratory time (IT), and the inspiratory gas flow (V Ti/IT) were measured every 5 min. Data were averaged during four 15 min periods before (P1 and P2) and after the incision (P3 and P4). Serial blood-gas analyses were also performed. Recoveries were unassisted, video recorded, and scored by three anesthetists blinded to the treatment. The postoperative behavior of the horses (25 demeanors), HR, and f R were recorded at three time points before induction (T0-24 h, T0-12 h, and T0-2 h) and six time points after recovery (TR) (TR + 2, 4, 6, 12, 24, 48 h). Data were compared between groups using a Wilcoxon test and within groups using a Friedman test or a Kruskal-Wallis signed-rank test when applicable. Tidal volumes (V Te and V Ti) were higher in PRE than in POST during all the considered periods but the difference between groups was only significant during P2 (V Te in mL kg(-1) in PRE: 13 [9, 15], in POST: 9 [8, 9], p = 0.01). None of the other variables were significantly different between and within groups. Under our experimental conditions, skin incision did not affect respiratory variables. Administration of pre- versus postoperative phenylbutazone and morphine did not influence recovery quality, HR, f R, or animal behavior.

Biological permeable reactive barriers coupled with electrokinetic soil flushing for the treatment of diesel-polluted clay soil.

Removal of diesel from spiked kaolin has been studied in the laboratory using coupled electrokinetic soil flushing (EKSF) and bioremediation through an innovative biological permeable reactive barriers (Bio-PRBs) positioned between electrode wells. The results show that this technology is efficient in the removal of pollutants and allows the soil to maintain the appropriate conditions for microorganism growth in terms of pH, temperature, and nutrients. At the same time, EKSF was demonstrated to be a very interesting technology for transporting pollutants, microorganisms and nutrients, although results indicate that careful management is necessary to avoid the depletion of nutrients, which are effectively transported by electro-migration. After two weeks of operation, 30% of pollutants are removed and energy consumption is under 70 kWh m(-3). Main fluxes (electroosmosis and evaporation) and changes in the most relevant parameters (nutrients, diesel, microorganisms, surfactants, moisture conductivity and pH) during treatment and in a complete post-study analysis are studied to give a comprehensive description of the most relevant processes occurring in the soil (pollutant transport and biodegradation).

Lactic acid bacteria isolated from young calves--characterization and potential as probiotics.

Lactic acid bacteria (LAB) are widely used as probiotics in humans and animals to restore the ecological balance of different mucosa. They help in the physiological functions of newborn calves that are susceptible to a variety of syndromes. The criteria for the selection of strains for the design of probiotic products are not available. Based in the host-specificity of the indigenous microbiota, 96 LAB isolates from faeces and oral cavity of calves were obtained. The surface properties were screened showing a small number of highly hydrophobic or autoagglutinating isolates. Also, a group produced H(2)O(2) and were able to inhibit pathogens, and two strains were bacteriocin-producers. Some grew at very low pH and high bile concentrations. The strains sharing some of the specific properties evaluated were identified genetically, assayed their compatibility and exopolysaccharide production. The results allow going further in the establishment of criteria to select strains to be included in a multi-strain-probiotic-product to be further assayed in animals.

Aryloxoalcanoic compounds induce resistance to antibiotic therapy in urinary tract infection caused by Escherichia coli.

Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and ethacrynic acid (ET) is administered to enhance diuresis. These compounds are structurally analogous to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), as they have a chlorinated phenoxy moiety. As these agents are mainly excreted by the renal route, they could potentially coexist with Escherichia coli in the urinary tract of infected patients. Induction of the in vitro resistance of E. coli to hydrophilic antibiotics was determined by increasing the values of the minimum inhibitory concentration (2-40-fold). These results correlated with drastically inhibited expression of the hydrophilic bacterial channel OmpF. In vivo assays were performed in ascending urinary tract infection in female BALB/c mice. Treatment with the hydrophilic antibiotic cephalexin 25 mg kg(-1) day(-1) by the oral route diminished renal infection. The CFU mean values in the kidneys were between 75% and 89% lower than those in animals without treatment. Simultaneous exposure to CL (at a therapeutic dose, 28.6 mg kg(-1) day(-1)) did not change the effect of the treatment. In contrast, ET at 2.9 mg kg(-1) day(-1) or 2,4-D at 70 mg kg(-1) day(-1) inhibited the antibiotic therapeutic effect. Moreover, 2,4-D dramatically increased bacterial infection after 9 days of exposure.

Clofibric and ethacrynic acids prevent experimental pyelonephritis by Escherichia coli in mice.

Interfering Escherichia coli attachment to the urinary tract, using P-fimbriation inhibitors, can prevent pyelonephritis. Clofibric and ethacrynic acids are organic compounds structurally related, but with different pharmacological uses. These agents are potentially active in the urinary tract due to its elimination in an unaltered form by the renal route. This study described a pyelonephritogenic E. coli strain, grown in the presence of sub-inhibitory concentrations of clofibric or ethacrynic acids (0.1 and 1 mM, respectively), which exhibits inhibition of P1 erythrocytes agglutination and a drastic decrease in fimbriation, using electron microscopy and quantitative analyses of superficial proteins (decrease to a 17-25% in comparison with the control). In vivo assays were performed using ascending urinary tract infection in mice. The treatment with therapeutic doses of the drugs, administered 2 days before the bacterial challenge and daily until the end of the experiment (22 days), abolished renal infection after 7-10 days of drug exposure. Within this period clofibric acid did not produce adverse effects on the renal parenchyma. However, ethacrynic acid caused pyelitis and tubular cellular desquamation. These results suggested that clofibric acid might be useful in the short-term prophylaxis of urinary tract infection.

Effect of the herbicide 2,4-dichlorophenoxyacetic acid on uropathogenic Escherichia coli virulence factors.

The effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D)-widely used in the world and mainly excreted by the renal route in exposed humans-were studied on the virulence and surface characteristics of an uropathogenic Escherichia coli strain. When the urine was supplemented with 2,4-D in vitro, the compound significantly reduced the bacterial fimbriation assayed by hemagglutination and surface protein quantification. Protein values decreased from 0.24 mg/g dw to 0.05 or 0.12 mg/g dw by 1 or 0.1 mM 2,4-D treatment, respectively. The effects in vivo were studied in groups of mice challenged intra-urethra with E. coli and exposed by the oral route with three different 2,4-D doses (2.6, 25 or 70 mg/kg bw) during 22 days. Depending on the dose used, the herbicide significantly decreased or removed bacterial cells in mice bladder and kidneys; except in the group treated with the highest dose from the 9th day of treatment. The histological studies showed mononuclear cell infiltration at low doses, and toxic damage in the renal parenchyma at prolonged exposure with higher doses, up to tisular necrosis in the 70 mg/kg bw group after 9 days of treatment. Our investigations performed in an experimental model suggest that short time 2,4-D exposure at low doses could act in prevention of UTI stimulating leukocytic migration and decreasing bacterial fimbriation. On the contrary, high doses and long-term exposure enhanced renal damage resulting in infection recurrence.