Psoriatic Patient-Reported Outcomes, Adherence, and Satisfaction. / Resultados comunicados por el paciente, adherencia y satisfacción en pacientes con psoriasis.

BACKGROUND: Patient-reported outcomes (PROs) are outcomes evaluated by patients based on their perception of their disease and treatment. OBJECTIVES: Determine antipsoriatic treatment-related adherence, quality of life (QoL) and satisfaction. MATERIALS AND METHODS: We conducted an observational cross-sectional, prospective, and single-center study in which PROs surveys were conducted on adherence (Morisky-Green [MG] test), treatment satisfaction (Spanish Questionnaire of Treatment Satisfaction in Psoriasis [CESTEP]) and QoL (Skindex-29 and DLQI). Additional variables include: PASI, BSA. STATISTICAL ANALYSIS: Jamovi®2.3.26. RESULTS: A total of 100 surveys were conducted. Based on the MG questionnaire, we found that 75% (75/100) of patients were adherent vs 94% (94/100) from the dispensation records. Regarding CESTEP, a mean score of 7.4±7.7 (close to maximum satisfaction 0) was obtained, while DLQI yielded a score of 2.6±4.6 (indicating a small effect on QoL), and SKINDEX-29 a score of 14.6±15.4 (68% indicating mild (< 5) or very mild (6-17) impact according to Nijsten et al.). Based on CESTEP a p.Rho Spearman value of 0.338 (p=0.004) was obtained in relation to PASI when the study was conducted with a BSA of 0.255 (p=0.050), DLQI results of 0.508 (p <0.001) and Skindex-29 results of 0.397(p <0.001). At the time of the study, the correlation matrix between DLQI result and PASI was 0.365 (p=0.002) with a BSA of 0.347 (p=0.007). Skindex-29 results with PASI were 0.380 (p=0.001) and with BSA, 0.295 (p=0.022). CONCLUSIONS: Patients on therapy exhibit a good QoL, high adherence and satisfaction with their treatment. A significant correlation was seen among satisfaction, QoL, and PASI-BSA at the time of the study.

Pax3 loss of function delays tumour progression in kRAS-induced zebrafish rhabdomyosarcoma models.

Rhabdomyosarcoma is a soft tissue cancer that arises in skeletal muscle due to mutations in myogenic progenitors that lead to ineffective differentiation and malignant transformation. The transcription factors Pax3 and Pax7 and their downstream target genes are tightly linked with the fusion positive alveolar subtype, whereas the RAS pathway is usually involved in the embryonal, fusion negative variant. Here, we analyse the role of Pax3 in a fusion negative context, by linking alterations in gene expression in pax3a/pax3b double mutant zebrafish with tumour progression in kRAS-induced rhabdomyosarcoma tumours. Several genes in the RAS/MAPK signalling pathway were significantly down-regulated in pax3a/pax3b double mutant zebrafish. Progression of rhabdomyosarcoma tumours was also delayed in the pax3a/pax3b double mutant zebrafish indicating that Pax3 transcription factors have an unappreciated role in mediating malignancy in fusion negative rhabdomyosarcoma.

Preclinical evaluation of the effects on the gastrointestinal tract of the antineoplastic drug vincristine repeatedly administered to rats.

BACKGROUND: Vincristine is a commonly used chemotherapeutic agent. It is associated with undesirable digestive side effects. However, the impact of vincristine on gastrointestinal structure and motility or its long-term effects have not been deeply studied in animal models. This could be useful in order to develop therapeutic or preventive strategies for cancer patients. The aim of this study was to analyze such effects. METHODS: Rats received saline or vincristine (0.1 mg kg-1 , ip) daily for 10 days. Evaluations were performed during treatment and 2-6 weeks after. Somatic mechano-sensitivity was assessed using von Frey hairs. Gastrointestinal motor function was studied by means of radiographic still images and colonic propulsion of fecal pellets using fluoroscopy videos. Histological assessment of the gut morphology and immunohistochemistry for HuC/D and nNOS were performed in whole-mount myenteric plexus preparations. KEY RESULTS: Peripheral sensitivity was increased in animals treated with vincristine and did not subside 2 weeks after treatment finalization. Vincristine treatment inhibited gastrointestinal motility although this was recovered to normal values with time. Damage in the digestive wall after vincristine treatment was greater in the ileum than in the colon. Villi shortening (in ileum) and large inflammatory nodules still remained 2 weeks after treatment finalization. Finally, the proportion of nNOS-immunoreactive neurons was increased with vincristine and continued to be increased 2 weeks after treatment finalization. CONCLUSIONS AND INFERENCES: Vincristine alters gastrointestinal motility, peripheral sensitivity and mucosal architecture. Vincristine-induced neuropathy (somatic and enteric), intestinal mucosa damage and inflammatory infiltrations are relatively long-lasting.

[Valproate-induced hyperammonemic encephalopathy]. / Encefalopatia hiperamonemica inducida por acido valproico.

TITLE: Encefalopatia hiperamonemica inducida por acido valproico.

Computer vision-based diameter maps to study fluoroscopic recordings of small intestinal motility from conscious experimental animals.

BACKGROUND: When available, fluoroscopic recordings are a relatively cheap, non-invasive and technically straightforward way to study gastrointestinal motility. Spatiotemporal maps have been used to characterize motility of intestinal preparations in vitro, or in anesthetized animals in vivo. Here, a new automated computer-based method was used to construct spatiotemporal motility maps from fluoroscopic recordings obtained in conscious rats. METHODS: Conscious, non-fasted, adult, male Wistar rats (n=8) received intragastric administration of barium contrast, and 1-2 hours later, when several loops of the small intestine were well-defined, a 2 minutes-fluoroscopic recording was obtained. Spatiotemporal diameter maps (Dmaps) were automatically calculated from the recordings. Three recordings were also manually analyzed for comparison. Frequency analysis was performed in order to calculate relevant motility parameters. KEY RESULTS: In each conscious rat, a stable recording (17-20 seconds) was analyzed. The Dmaps manually and automatically obtained from the same recording were comparable, but the automated process was faster and provided higher resolution. Two frequencies of motor activity dominated; lower frequency contractions (15.2±0.9 cpm) had an amplitude approximately five times greater than higher frequency events (32.8±0.7 cpm). CONCLUSIONS & INFERENCES: The automated method developed here needed little investigator input, provided high-resolution results with short computing times, and automatically compensated for breathing and other small movements, allowing recordings to be made without anesthesia. Although slow and/or infrequent events could not be detected in the short recording periods analyzed to date (17-20 seconds), this novel system enhances the analysis of in vivo motility in conscious animals.

Prevalence and Phylogenetic Analysis of Bartonella Species of Wild Carnivores and Their Fleas in Northwestern Mexico.

The host-parasite-vector relationship of Bartonella spp. system in wild carnivores and their fleas from northwestern Mexico was investigated. Sixty-six carnivores belonging to eight species were sampled, and 285 fleas belonging to three species were collected during spring (April-May) and fall (October-November) seasons. We detected Bartonella species in 7 carnivores (10.6%) and 27 fleas (9.5%) through either blood culture or PCR. Of the 27 Bartonella-positive fleas, twenty-two were Pulex simulans, three were Pulex irritans and one was Echidnophaga gallinacea. The gltA gene and ITS region sequences alignment revealed six and eight genetic variants of Bartonella spp., respectively. These variants were clustered into Bartonella rochalimae, Bartonella vinsonii subsp. berkhoffii and another genotype, which likely represents a novel species of Bartonella spp. Although experimental infection studies are required to prove the vector role of P. simulans, our results suggest that this flea may play an important role in the Bartonella transmission. The results indicated possible host-specific relationships between Bartonella genotypes and the families of the carnivores, but further studies are needed to verify this finding. The presence of zoonotic species of Bartonella spp. in wild carnivores raises the issue of their potential risk for humans in fragmented ecosystems.

May cannabinoids prevent the development of chemotherapy-induced diarrhea and intestinal mucositis? Experimental study in the rat.

BACKGROUND: The antineoplastic drug 5-fluoruracil (5-FU) is a pirimidine analog, which frequently induces potentially fatal diarrhea and mucositis. Cannabinoids reduce gastrointestinal motility and secretion and might prevent 5-FU-induced gut adverse effects. Here, we asked whether cannabinoids may prevent diarrhea and mucositis induced by 5-FU in the rat. METHODS: Male Wistar rats received vehicle or the non-selective cannabinoid agonist WIN 55,212-2 (WIN; 0.5 mg kg-1 injection-1 , 1 injection day-1 , 4 consecutive days) by intraperitoneal (ip) route; on the first 2 days, animals received also saline or 5-FU (150 mg kg-1 injection-1 , cumulative dose of 300 mg kg-1 ). Gastrointestinal motor function was radiographically studied after barium contrast intragastric administration on experimental days 1 and 4. Structural alterations of the stomach, small intestine and colon were histologically studied on day 4. PAS staining and immunohistochemistry for Ki67, chromogranin A and CD163 were used to detect secretory, proliferating, and endocrine cells, and activated macrophages respectively. KEY RESULTS: As shown radiographically, 5-FU induced significant gastric emptying delay (on days 1 and 4) and diarrhea (on day 4). WIN did not significantly alter the motility curves obtained for either control or 5-FU-treated animals but tended to reduce the severity of 5-FU-induced diarrhea and increased permanence of barium from day 1 to the beginning of day 4 in 5-FU-treated animals. 5-FU-induced mucositis was severe and not counteracted by WIN. CONCLUSIONS AND INFERENCES: 5-FU-induced diarrhea, but not mucositis, was partly prevented by WIN at a low dose. Cannabinoids might be useful to prevent chemotherapy-induced diarrhea.

In vitro and non-invasive in vivo effects of the cannabinoid-1 receptor agonist AM841 on gastrointestinal motor function in the rat.

BACKGROUND: Cannabinoids have been traditionally used for the treatment of gastrointestinal (GI) symptoms, but the associated central effects, through cannabinoid-1 receptors (CB1R), constitute an important drawback. Our aims were to characterize the effects of the recently developed highly potent long-acting megagonist AM841 on GI motor function and to determine its central effects in rats. METHODS: Male Wistar rats were used for in vitro and in vivo studies. The effect of AM841 was tested on electrically induced twitch contractions of GI preparations (in vitro) and on GI motility measured radiographically after contrast administration (in vivo). Central effects of AM841 were evaluated using the cannabinoid tetrad. The non-selective cannabinoid agonist WIN 55,212-2 (WIN) was used for comparison. The CB1R (AM251) and CB2R (AM630) antagonists were used to characterize cannabinoid receptor-mediated effects of AM841. KEY RESULTS: AM841 dose-dependently reduced in vitro contractile activity of rat GI preparations via CB1R, but not CB2R or opioid receptors. In vivo, AM841 acutely and potently reduced gastric emptying and intestinal transit in a dose-dependent and AM251-sensitive manner. The in vivo GI effects of AM841 at 0.1 mg/kg were comparable to those induced by WIN at 5 mg/kg. However, at this dose, AM841 did not induce any sign of the cannabinoid tetrad, whereas WIN induced significant central effects. CONCLUSIONS & INFERENCES: The CB1R megagonist AM841 may potently depress GI motor function in the absence of central effects. This effect may be mediated peripherally and may be useful in the treatment of GI motility disorders.

Effects of chronic dietary exposure to monosodium glutamate on feeding behavior, adiposity, gastrointestinal motility, and cardiovascular function in healthy adult rats.

BACKGROUND: Monosodium glutamate (MSG) is a flavor-enhancer widely used as a food additive. However, its safe dietary concentration and its toxicity, including its possible implication in the recent metabolic syndrome pandemia, is still a controversial issue. Therefore, a deep knowledge of its effects upon regular dietary use is needed. Our aim was to evaluate the effects of chronic exposure to MSG on feeding behavior, abdominal fat, gastrointestinal motility, and cardiovascular function in rats. METHODS: Two groups of adult male Wistar rats were used: control and treated with MSG (4 g/L in drinking water) for 6 weeks. Different functional parameters were determined and the histological structure was analyzed in tissues of interest. KEY RESULTS: Compared to control animals, chronic MSG increased water intake but did not modify food ingestion or body weight gain. Neither the abdominal fat volume nor the fat fraction, measured by magnetic resonance imaging, was modified by MSG. Monosodium glutamate did not alter general gastrointestinal motility, but significantly increased the colonic response to mechanical stimulation. It slightly reduced endothelium-dependent relaxation in aorta, without significantly modifying any other cardiovascular parameters. No significant histological alterations were detected in salivary glands, intestinal wall, aorta, heart, and kidney. CONCLUSIONS & INFERENCES: Chronic treatment with MSG in the adult rat increased water intake. This supports its potential to improve acceptance of low-fat regimens and to increase hydration in the elderly and sportspeople, often at risk of dehydration. Changes in colonic contractility and cardiovascular function could have some long-term repercussions warranting further research.

Synthesis and complementary self-association of novel lipophilic π-conjugated nucleoside oligomers.

A series of lipophilic nucleosides comprising natural and non-natural bases that are π-conjugated to a short oligophenylene-ethynylene fragment has been synthesized. These bases comprise guanosine, isoguanosine, and 2-aminoadenosine as purine heterocycles, and cytidine, isocytosine and uridine as complementary pyrimidine bases. The hydrogen-bonding dimerization and association processes between complementary bases were also studied by (1)H NMR and absorption spectroscopy in order to obtain the relevant association constants.

Cannabinoids may worsen gastric dysmotility induced by chronic cisplatin in the rat.

BACKGROUND: Although cannabinoids have traditionally been used for the treatment and/or prevention of nausea and/or emesis, anorexia and weight loss induced by clinical use of antineoplastic drugs, their efficacy and safety in long-term treatments are still controversial. Our aim was to analyze the effects of the non-selective cannabinoid agonist WIN 55 212-2 (WIN) on gastrointestinal (GI) dysmotility and other adverse effects induced by repeated cisplatin administration in the rat. METHODS: Male Wistar rats received two intraperitoneal injections once a week for 4 weeks: the first one was WIN, at non-psychoactive doses (0.5 or 1 mg kg(-1)), its vehicle or saline; the second one was cisplatin (2 mg kg(-1)) or saline. Radiographic techniques were used to determine the acute (after first dose), chronic (after last dose), and residual (1 week after treatment finalization) effects of cisplatin and/or WIN on GI motility. Bodyweight gain, food ingestion, and mechanical sensitivity were also tested. KEY RESULTS: Weekly cisplatin induced mechanical allodynia, which WIN prevented, as well as weight gain reduction and anorexia, which WIN did not. Gastric emptying was dose-dependently delayed by cisplatin and this effect was enhanced upon chronic treatment. WIN aggravated cisplatin-induced gastric dysmotility. One week after treatment finalization, only minor alterations of GI motor function were found in rats treated with cisplatin, WIN or both. CONCLUSIONS & INFERENCES: WIN weekly administered at low doses prevents neuropathy, but does not prevent anorexia or weight loss and aggravates gastric dysmotility induced by cisplatin. Cannabinoids should be handled with caution if chronically administered during chemotherapy.

Ram seminal plasma improves pregnancy rates in ewes cervically inseminated with ram semen stored at 5 °C for 24 hours.

In this study, we compared pregnancy rates obtained using ram semen stored at 5 °C for 24 h, with ram or bull seminal plasma (SP) added to TRIS-egg yolk extender. During the breeding period, 670 adult Corriedale ewes were cervically inseminated with semen (2 × 10(8) sperm in a volume of 0.2 mL) from eight adult Corriedale rams. Ejaculates, obtained using an artificial vagina, were split into three aliquots and diluted with the following: TRIS-egg yolk based extender (T), T + 30% ram SP (R), or T + 30% bull SP (B). Samples were refrigerated and stored at 5 °C for 24 h until used for AI. Pregnancy was assessed by ultrasonography 35 to 40 d after AI. Pregnancy rate was not affected by ram (P = 0.77) or breeding period (P = 0.43), and there were no interactions between extender and ram (P = 0.94), or extender and breeding period (P = 0.24). However, there was an effect of extender (P = 0.0009) on pregnancy rates; ram SP, but not bull SP, increased pregnancy rates compared with extender without SP (49.7, 38.1, and 31.1%, for R, B, and T respectively). In conclusion, ram SP added to TRIS-egg yolk extender had a beneficial effect on the pregnancy rate of ram sperm stored at 5 °C for 24 h and used for cervical insemination of ewes.

[Epidural analgesia in obstetrics: is there an effect on labor and delivery?]. / Analgesia epidural en obstetricia: cómo afecta al desarrollo y finalización del parto?

BACKGROUND AND OBJECTIVE: Epidural analgesia is routinely used in obstetrics but has been blamed for possible effects on labor that lead to greater use of instruments or conversion to cesarean delivery. We aimed to assess this possibility in a cohort of obstetric patients receiving or not receiving epidural analgesia. PATIENTS AND METHODS: Prospectively enrolled full-term obstetric patients were distributed in 2 groups according to whether they received epidural analgesia or not. We compared maternal and fetal characteristics, obstetric variables, and type of delivery between groups to record the likely causes of difficult labor and delivery and detect a possible influence of epidural analgesia. RESULTS: Of a total of 602 patients, 462 received epidural analgesia and 140 did not. Epidural analgesia was related to a higher rate of use of instruments but not cesareans (P < .01) and more frequent need for oxytocin (30.7% of the epidural analgesia group vs 0% of the group receiving no epidural analgesia, P < .001). The women receiving analgesia also had a longer mean (SD) duration of the dilatation phase of labor (6.4 [4.2] hours in the epidural group vs 4.7 [3.5] hours in the no-epidural group, P < .01) and of the expulsion phase (1.0 [0.6] hours vs 0.7 [0.6] hours, respectively; P<.01). We observed no effects on the incidence of tearing, rate of episiotomy, or other variables. Predictors of instrumentation or conversion to cesarean delivery were longer duration of the first phase (odds ratio [OR] 1.2; 95% confidence interval [CI], 1.1-1.3), longer duration of the second phase (OR 2.3; 95% CI, 1.3-3.9), and maternal obesity (OR, 1.1; 95% CI, 0.9-1.2). Previous deliveries and initiation of epidural analgesia after the fetus has reached Hodge's first plane decreased risk 2.7-fold and 3.03-fold, respectively. CONCLUSIONS: Although epidural analgesia has traditionally been associated with a higher incidence of difficult labor and delivery, this association was not unequivocally evident in this cohort of patients. The apparent increase seems to be attributable to such obstetric factors as longer duration of stages of labor, higher body mass index, and first delivery.

New method to enhance ajmalicine production in Catharanthus roseus cell cultures based on the use of cyclodextrins.

The joint use of cyclodextrins and methyljasmonate, when accompanied by a short exposure to UV, enhanced extracellular ajmalicine accumulation to 1040 ± 26.6 mg/l in suspension cultured cells of Catharanthus roseus. The success of this strategy is due to the use of cyclodextrins, which not only induce ajmalicine biosynthesis but also promote adduct formation. This removes ajmalicine from the medium, reduces feedback inhibition and ajmalicine degradation, and allows its accumulation in the culture medium at elevated concentrations.

[Efficacy of obturator and femoral cutaneous nerve blocks for postoperative analgesia in hip surgery]. / Eficacia del bloqueo de los nervios obturador y femorocutáneo para analgesia postoperatoria en cirugía de cadera.

OBJECTIVES: The treatment of pain after surgery to repair a hip fracture is essential for an early start of rehabilitation and for reducing morbidity and mortality. Given that patients are elderly and have multiple medical conditions, local-regional analgesia can be an effective approach. Our aim was to compare the efficacy of obturator and femoral cutaneous nerve blocks and total intravenous analgesia in terms of level of patient satisfaction, complications, start of rehabilitation, and cost. PATIENTS AND METHODS: Prospective study of 75 patients undergoing surgery to repair hip fractures. Patients were randomized to receive intravenous analgesia only, blockade of both nerves, or blockade of only the obturator nerve. In each group we recorded visual analog scale (VAS) pain scores, satisfaction with postoperative analgesia, time elapsed until start of rehabilitation, need for postoperative analgesics, side effects, and the cost of drugs. RESULTS: Analgesia was significantly more effective in patients with nerve blocks than in those who received only intravenous analgesia (mean [SD] VAS scores, 2.6 [1.4] and 5.6 [0.7], respectively). Patients with nerve blocks also had a pain-free period of more than 24 hours (P < .001), needed fewer doses of supplementary analgesics or other drugs, had fewer side effects (P < .01), started rehabilitation earlier (32.6 [5.4] hours vs 45.7 [8.2] hours), generated less expenditure (2.6 Euros [1.5 Euros]/patient vs 7.0 Euros [0.4 Euros]/patient). The tested techniques had no complications. CONCLUSIONS: The nerve blocks were effective, easy to perform, and safe. They afforded numerous advantages: extended period of postoperative analgesia, fast recovery, lower costs, and no complications.

[Hypovolemic shock due to spontaneous hemorrhage associated with heparin anticoagulant treatment; a report of 5 cases]. / Shock hipovolémico por hemorragia espontánea asociada a tratamiento anticoagulante con heparina; presentación de cinco casos.

Hypovolemic shock occasioned for the spontaneous hemorrhage is a complication very rare in the course of the anticoagulant therapy with heparin. We are going to introduce you five cases where a therapy with heparin produced spontaneous hemorrhage and hypovolemic shock. We noticed them in our Intensive Medicine Service in five the last ones years. In all the patients we found helping factors of hemorrhage. In two of the patients the hemorrhage took place in spite of to maintain an activated partial-thromboplastin time (APTT) inside the therapeutic range of anticoagulation; another two presented a APTT excessively elongated; and a patient had it completely normal. In all the cases the hemoglobin and hematocrit values were normals at the beginning; however the pain ws always in all the patients and gave us an idea about the place where the bleeding was. In a patient the computed tomographic (CT) confirmed the diagnosis. In two cases the treatment was surgical. We explain coadyuvanted factors that are required in the hemorrhage genesis in anticoagulated patients with heparin.

[Unusual association of malakoplakia and renal polycystosis. A case report]. / Rara asociación de malakoplakia y poliquistosis renal. A propósito de un caso.

We report a case of malakoplakia coexisting with renal polycystosis, a rare association that had been histologically demonstrated in a patient who developed end-stage renal failure. This condition is reviewed highlighting its localization and coexisting conditions, and the different hypotheses relative to its pathogenesis are discussed. A better understanding of the metabolic and immunologic aspects have provided further insight relative to treatment. Furthermore, there appears to be an increasing tendency towards nosologic and clinical unification of different syndromes with changes in bacterial phagocytosis coexisting or secondary to immune changes.