Endothelial KCa channels: Novel targets to reduce atherosclerosis-driven vascular dysfunction.

Elevated levels of cholesterol in the blood can induce endothelial dysfunction, a condition characterized by impaired nitric oxide production and decreased vasodilatory capacity. Endothelial dysfunction can promote vascular disease, such as atherosclerosis, where macrophages accumulate in the vascular intima and fatty plaques form that impair normal blood flow in conduit arteries. Current pharmacological strategies to treat atherosclerosis mostly focus on lipid lowering to prevent high levels of plasma cholesterol that induce endothelial dysfunction and atherosclerosis. While this approach is effective for most patients with atherosclerosis, for some, lipid lowering is not enough to reduce their cardiovascular risk factors associated with atherosclerosis (e.g., hypertension, cardiac dysfunction, stroke, etc.). For such patients, additional strategies targeted at reducing endothelial dysfunction may be beneficial. One novel strategy to restore endothelial function and mitigate atherosclerosis risk is to enhance the activity of Ca2+-activated K+ (KCa) channels in the endothelium with positive gating modulator drugs. Here, we review the mechanism of action of these small molecules and discuss their ability to improve endothelial function. We then explore how this strategy could mitigate endothelial dysfunction in the context of atherosclerosis by examining how KCa modulators can improve cardiovascular function in other settings, such as aging and type 2 diabetes. Finally, we consider questions that will need to be addressed to determine whether KCa channel activation could be used as a long-term add-on to lipid lowering to augment atherosclerosis treatment, particularly in patients where lipid-lowering is not adequate to improve their cardiovascular health.

Putative Meiotic Toolkit in the Dinoflagellate Prorocentrum cordatum: Additional Evidence for Sexual Process from Transcriptome.

Prorocentrum cordatum (Ostenfeld) Dodge-is a planktonic armored dinoflagellate that is a bloom-forming, potentially toxic cosmopolitan species. The transition from vegetative reproduction to the sexual process has been recently shown for this organism. Here, we present the results of transcriptomic data analysis that uncovered one syngamy-associated and 16 meiosis-associated proteins in P. cordatum. We also detected an amino acid sequence homologous to bacterial MutS2 protein. The MutS2 presence and origin in dinoflagellates are discussed for the first time.

Features of some anthropometric indices and indices of insulin resistance in patients with non-alcoholic steatohepatitis on the background of obesity and osteoarthritis.

OBJECTIVE: The aim: To estimate the diagnostic and predictive value of anthropometric indices indicating obesity and glycemic parameters in the progression of NASH due to comorbidity with OA and OB. PATIENTS AND METHODS: Materials and methods: 90 patients were examined and distributed into three groups: group 1 included patients suffering from OA, grade II-III according to Kellgren and Lawrense classification, with normal body mass, group 2 -patients with NASH and obesity without OA, group 3 -patients with OA, NASH and obesity. The control group consisted of 30 healthy individuals of the corresponding age. RESULTS: Results: There was a correlation between lipid and carbohydrate metabolism. This fact was confirmed by the evidence that under the influence of IR there was an increase in the level of lipoproteins enriched in triglycerides, the concentration of cholesterol of low density lipoprotein and reduction in level cholesterol of high density lipoprotein, which led to the progression of the clinical course of NASH. It was established that anthropometric indices of patients with comorbid flow of NASH, OA and OB were significantly (p <0.05) higher than in experimental groups. A positive correlation was found between some anthropometric indices and the following glycemic parameters: fasting blood glucose, HOMA-IR suggested that insulin resistance contributed to the growth of glycated compounds leading not only to the progression of NASH and affect the dysfunction of chondrocytes, but also influencing destruction of subchondral bone in osteoarthritis. CONCLUSION: Conclusions: The outcomes of the study result in the necessity of studying the metabolic status in patients with a comorbid progression of NASH, OB and OA for timely correction of the revealed disorders, which will reduce the run of NAFLD.

A Phase 2 Randomized Trial of DCL-101, a Novel Pill-Based Colonoscopy Prep, vs 4L Polyethylene Glycol-Electrolyte Solution.

INTRODUCTION: DCL-101, a novel Pill Prep, is compositionally identical to standard 4L polyethylene glycol-electrolyte solution (PEG-ELS) and delivers the salt encapsulated, with PEG 3350 coadministered as a taste-free oral solution. The aim of this study was to compare the safety, taste, and tolerability of DCL-101 with 4L PEG-ELS in outpatients preparing for colonoscopy, with a secondary objective to assess efficacy. METHODS: This was a multicenter, randomized, investigator-blinded, phase 2 clinical trial of 45 adult patients undergoing outpatient colonoscopy. Patients were randomized 2:1 to either DCL-101 (3L in cohort 1; 4L in cohort 2) or 4L PEG-ELS, each administered with split dosing. Safety was assessed over 3 post-treatment clinic visits. Tolerability was measured using the Lawrance Bowel-Preparation Tolerability Questionnaire and the Mayo Clinic Bowel Prep Tolerability Questionnaire. Efficacy was determined by expert central readers, blinded to treatment, using the Ottawa Bowel Preparation Quality Scale, Boston Bowel Preparation Scale, and Aronchick scale. RESULTS: Both DCL-101 doses had superior taste and tolerability relative to 4L PEG-ELS. All adverse events were grade 1 with no significant differences in adverse events among the 3 regimens. There were no significant differences in efficacy among the 3 treatments as defined by the centrally read Ottawa Bowel Preparation Quality Scale, Boston Bowel Preparation Scale, or Aronchick scores. There were no inadequate preps as judged by the site endoscopist. DISCUSSION: DCL-101 Pill Prep is a novel strategy that vastly improves the taste and tolerability of PEG-ELS solutions with safety and efficacy comparable with split-dose 4L PEG-ELS solutions.

Reacción adversa causada por fármacos antituberculosos en un paciente con tuberculosis pulmonar y meníngea / Adverse reaction caused by antituberculosis drugs in a patient with pulmonary and meningous tuberculosis

Las reacciones por hipersensibilidad a fármacos constituyen una condición que genera cuadros muy diversos. Se presenta un caso clínico de reacción adversa a fármacos antituberculosos (RAFA) de tipo alérgica en una mujer adulta con diagnóstico de tuberculosis (TB). La identificación y supresión de los fármacos causantes de la RAFA permitió redireccionar y finalizar el tratamiento con excelente evolución clínica

The hypersensitivity reactions to drugs constitute a condition that generates very diverse clinical signs and symptoms. A clinical case of an adverse reaction to antituberculosis drugs of an allergic type in an adult woman with a diagnosis of tuberculosis (TB) is presented. The identification and suppression of the drugs causing the adverse reaction allowed to redirect and end the treatment with excellent clinical evolution

Extraction of source functions of surface photovoltage transients at very short times.

The measurement of surface photovoltage (SPV) transients over 12 orders of magnitude in time was recently demonstrated [Rev. Sci. Instrum. 88, 053904 (2017)]. In dedicated experiments, however, a high-impedance buffer shall be placed outside the measurement chamber, which has consequences for SPV measurements at very short times. By varying the LCR circuit of a measurement configuration, applying a multi-parameter fit and simulating the corresponding SPV transients, we show, on the examples of highly doped silicon and a CdS thin film, that the source function of SPV transients can be reconstructed with a resolution time better than 1 ns.

Wound Regeneration Deficit in Rats Correlates with Low Morphogenetic Potential and Distinct Transcriptome Profile of Epidermis.

Large excisional wounds in mice prominently regenerate new hair follicles (HFs) and fat, yet humans are deficient for this regenerative behavior. Currently, wound-induced regeneration remains a clinically desirable, but only partially understood phenomenon. We show that large excisional wounds in rats across seven strains fail to regenerate new HFs. We compared wound transcriptomes between mice and rats at the time of scab detachment, which coincides with the onset of HF regeneration in mice. In both species, wound dermis and epidermis share core dermal and epidermal transcriptional programs, respectively, yet prominent interspecies differences exist. Compared with mice, rat epidermis expresses distinct transcriptional and epigenetic factors, markers of epidermal repair, hyperplasia, and inflammation, and lower levels of WNT signaling effectors and regulators. When recombined on the surface of excisional wounds with vibrissa dermal papillae, partial-thickness skin grafts containing distal pelage HF segments, but not interfollicular epidermis, readily regenerated new vibrissa-like HFs. Together, our findings establish rats as a nonregenerating rodent model for excisional wound healing and suggest that low epidermal competence and associated transcriptional profile may contribute to its regenerative deficiency. Future comparison between rat and mouse may lend further insight into the mechanism of wounding-induced regeneration and causes for its deficit.

Apendicitis aguda en el niño / Acute appendicitis in children

"Los síntomas deben evaluarse y no contarse" PAYR. La apendicitis aguda del niño no tiene la evolución clínica de la del adulto. Los accidentes se suceden con mayor rapidez y adquieren mayor gravedad. Las condiciones de infección son las mismas que en el adulto; debe considerarse entonces el terreno como el factor que da a la infección un giro clínico diferente. Ombredanne y otros autores han establecido que el niño, en el curso de la apendicitis, con cierta frecuencia, tiene reacciones orgánicas diferentes a las del adulto. En verdad se sabe que pocas afecciones proporcionan la oportunidad de que se cometan tan variados errores de diagnóstico como las enfermedades del apéndice. Ello se debe a la situación muy variable de este órgano y sus relaciones anatómicas con las partes vecinas, al distinto grado de las alteraciones anatomo-patológicas y a la irregularidad, a la inconstancia y a la vaguedad con que muchas veces se presentan algunos de sus síntomas (Schwal-be).

Detection of zoonotic intestinal parasites in public parks of Spain. Potential epidemiological role of microsporidia.

Several studies have demonstrated that the soil of public parks presents an important source of infection which has a significant impact on public health. Children are the main group affected by accidentally ingestion of contaminated soil. This study was performed in order to identify the presence of zoonotic parasites in dog and cat faecal and soil samples from public parks of Madrid, Spain. Six hundred twenty-five and seventy-nine soil and faecal samples (presumably from dogs and cats) respectively were collected from 67 parks. Intestinal parasites were identified in 27 parks (40.3%), which were contamined with Giardia sp. (19.4%), microsporidia (19.4%), Toxocara spp. (16.4%), Cryptosporidium sp. (6%), Entamoeba histolytica (3%) and Ancylostomidae (3%). Combinations of two or more intestinal parasites were found in 11 parks, and it was common to find Giardia and microsporidia together in samples. Intestinal parasites were detected in 18% (112/625) of soil samples. The most frequent parasite species found in the examined soil samples were Toxocara spp. (16.4%), followed by Giardia sp. (4.5%) and Strongyloides sp. larvae (3%). The zoonotic parasites found in the 79 faecal samples were Giardia sp. (17.7%), Cryptosporidium sp. (9%), E. histolytica (2.5%), Trichuris vulpis (1.3%), Toxascaris leonina (1.3%) and microsporidia spores (28%). Microsporidia characterization by amplification of DNA confirmed 10 samples as positive, eight for E. bieneusi and two for E. hellem by PCR. The role of those parasites in the environment are discussed.

Duplicación del apéndice vermiforme / Double appendix: case report

We report a 37 years old male presenting with an acute appendicitis. The patient was operated, excising a gangrenous and perforated appendix. During closure a second appendix that was not inflamed, located three cm apart from the first one, was observed. It was also excised and the pathologic report confirmed that both surgical pieces corresponded to appendices, one inflamed and the other normal.

Presentamos el caso de un paciente de 37 años de edad, con clínica de apendicitis aguda que tras apendicetomía se pesquisó duplicación del apéndice vermiforme. La histología reveló inflamación aguda de uno de ellos. Esta rara anomalía ha sido descrita en menos de 100 casos. Se requiere un conocimiento de este infrecuente cuadro quirúrgico para un reconocimiento oportuno, ya que un error puede significar graves consecuencias clínicas para el paciente y médico legales para el cirujano.

Secuelas de la trombosis venosa profunda de las extremidades inferiores luego de un tratamiento anticoagulante controlado / Sequels of deep venous thrombosis of the lower limbs after a controlled anticoagulant therapy

Objetivo: Con el fin de evaluar la eficacia de la anticoagulación "clásica" en prevenir las secuelas en el sistema venoso profundo luego de un primer episodio de trombosis venosa profunda (TVP), se efectuó un año después un control clínico y con ecodoppler color, a pacientes que habían sufrido una TVP tratada con Heparina y anticoagulantes orales. Material y método: Sesenta y dos pacientes (47 mujeres y 15 varones, promedio de edad 53,5 años) fueron ingresados en el Hospital Dr. Eduardo Pereira de Valparaíso durante el episodio inicial de trombosis confirmadas con ecodoppler color y tratados con heparina sódica o de bajo peso molecular. Luego se les sometió a un prolongado tiempo de tratamiento anticoagulante oral (TACO) controlado. Fueron clasificados en trombosis distales 13 pacientes (21 por ciento), fémoro-poplíteas 21 pacientes (33,9 por ciento) e ilio-fémoro-poplíteas 28 pacientes (45,2 por ciento). Se constató el tiempo transcurrido entre el comienzo de los síntomas y el inicio del tratamiento con heparina con un promedio de 9,8 días. Se evaluó también el grado de eficacia anticoagulante del TACO según el número de controles con un International Nornalized Ratio (INR) eficaz sobre 2,0. Se encontró un buen TACO en 40 pacientes (64,5 por ciento) (INR eficaz sobre el 75 por ciento de los controles), un TACO regular en 12 pacientes (19,4 por ciento) (INR eficaz menor del 75 por ciento, pero mayor del 50 por ciento en los controles) y un TACO malo en 10 pacientes (16,1 por ciento) (INR eficaz en menos de la mitad de los controles). Resultados: Entre 9 meses y un año después se efectuó un control clínico y con ecodoppler color a todos los pacientes. La evaluación clínica se realizó según la clasificación de Casanueva del Síndrome Post-trombótico. Veinticuatro pacientes (38,7 por ciento) de los pacientes (38,7 por ciento) de los pacientes se encontraban asintomáticos (grado 0), 30 (48,4 por ciento) presentaba sólo edema (grados 1 y 2), 4 (6,5 por ciento) presentaban edema y várices secundarias (grado 3) y 4 pacientes (6,5 por ciento) presentaban además lipodermatoesclerosis o úlceras de la pierna (grado 4). Las secuelas evaluadas con ecodoppler color fueron la insuficiencia valvular, la obliteración venosa y otras lesiones, como fibrosis parietales, bandas fibrosas intraluminales y estenosis con flujo venoso parcial...

El aporte de la cirugía bariátrica en el tratamiento del síndrome de Pickwick / Contribution of bariatric surgery in the treatment of Pickwick syndrome

El conjunto de alteraciones respiratorias que sufren los obesos mórbidos y que llevan a la hipoxemia e hipercapnia crónica, con poliglobulia compensatoria y falla cardíaca derecha secundaria es conocida desde hace tiempo como Síndrome de Pickwick. Su tratamiento médico es complejo y poco efectivo, siendo en la actualidad la cirugía bariátrica la que mejores resultados obtiene. En una serie de seis pacientes, con este cuadro, operados desde 1980 por el autor principal, sus resultados han sido muy satisfactorios al corregir rápida y efectivamente las graves alteraciones respiratorias presentes, corroborando lo descrito por la literatura mundial

Muscle fiber composition and capillarization in relation to metabolic alterations in hypertensive men.

The aim of this study was to determine if there is a relationship among skeletal muscle fiber composition, capillarization, blood pressure (BP) and/or the components of the metabolic syndrome. Two groups were compared: 8 recently diagnosed, untreated, hypertensive men (BP > or = 140/90) and 7 normotensive men as controls. Muscle biopsies were taken from the vastus lateralis part of quadriceps femoris muscle in order to assess: fiber type proportion, capillarization, hexokinase, citrate synthase, beta-hydroxyacyl CoA dehydrogenase activities; lipoprotein lipase mass and activity, free fatty acids and triglycerides. Serum levels of insulin, glucose, cholesterol, uric acid and triglycerides were also assayed. Hypertensive patients had higher insulin levels and insulin resistance [homeostasis model assessment (HOMA)], a decreased hexokinase activity and an increase of muscle lipoprotein lipase mass as compared to controls. Interestingly, correlations among values differ in each group. The percentage of type IIB fibers was related to diastolic BP (blood pressure) in control and to mean BP in hypertensive subjects. Serum cholesterol and glucose were inversely related to the percentage of type I fibers in the control subjects. Negative correlations between capillarization and glucose, cholesterol and uric acid levels were found in control subjects. In all subjects, a strong correlation was found between SBP (systolic BP) and DBP (diastolic BP), and insulin resistance (IR) and uric acid levels. Muscle fiber type proportion and capillarization were related to blood pressure and components of the metabolic syndrome.

Membrane NADPH Oxidase and Hormonal Regulation of the Immunocompetent Cell Functional Activity.

Effect of dexamethasone upon NADPH oxidase activity of murine thymocytes and the role of reactive oxygen species (ROS) were investigated in dexamethasone-induced thymocyte apoptosis. Hormonal stimulation of NADPH oxidase has been demonstrated in cell-free system (homogenate of thymocytes). The depletion of hydrogen peroxide, produced due to NADPH oxidase activity, with catalase addition has been shown to inhibit dexamethasone-induced thymocyte apoptosis. The key role of NADPH oxidase and NADPH oxidase-dependent ROS production in the development of lymphocyte apoptosis was confirmed in experiments with two inhibitors of this enzyme. It has been evidenced that both inhibitors used (diphenylene iodonium and cromolyn) violently inhibited glucocorticoid-induced lymphocyte apoptosis. The possibility of the direct extragenomic action of glucocorticoids upon ROS production in the cells is discussed, as well as the role of this effect in glucocorticoid-induced lymphocyte apoptosis.

Capillary changes in skeletal muscle of patients with essential hypertension.

Arterial hypertension produces changes along the vascular tree. However, there are few reports on its effect on human muscle capillaries. This study demonstrates the effects of essential hypertension on the capillaries of human quadriceps muscle. Muscle biopsy was taken from quadriceps femoris in eight men with recent diagnosis of essential hypertension, without treatment. Biopsies were also taken from eight normotensive men and were used as controls. Fiber types were classified by ATPase reaction, capillaries counted in alpha-amylase-PAS stained sections and ultrastructure studied by conventional methods of transmission electron microscopy. No changes were found in capillaries or muscle fiber types by histochemical methods. However, electron microscopy revealed abnormal capillaries with endothelial cells infoldings into the lumen, as well as occluded or degenerated capillaries. In some cases the endothelial cell area covered by pericytes was increased. Basement membrane of capillaries was frequently increased in width, sometimes irregularly, and in other instances it was reduplicated. In transversely sectioned capillaries lumen diameter was reduced and wall thickness was increased, although total diameter was unchanged. In hypertensive patients the finding of some degenerated capillaries adjacent to muscle fibers could be interpreted as the beginning of a process of rarefaction. Some capillaries showed morphological changes, and the ratio wall thickness/lumen was increased.

Wave parameters of the sperm flagellum as predictors of human spermatozoa motility.

We characterized the undulatory movement of the sperm's flagellum as a sigmoid wave by measuring the absolute and linear speed of the sperm, period, amplitude and length of the flagellum's wave, and the segment comprised between the head and the origin of the movement in the flagellum. These parameters were correlated with traditional ones used to determine the pattern of movement of the sperm. Our results show that wave parameters are useful predictors of sperm motility. They correlate among themselves, and thus, a few wave parameters may characterize the sperm motility. The advantage of wave parameters is that they can be easily obtained and can be eventually associated to the sperms' internal morphology.

Localization of the centromere protein CENP-B using scleroderma sera and evidence for a role in centromere survival.

OBJECTIVE: To determine whether centromeric CENP A, B and C proteins play a role in centromere survival. METHODS: Sixteen anti-centromere sera from scleroderma patients were used. The most common reactivity demonstrated by Western blot was anti-CENP-A, followed by anti-CENP-B and -C, in that order. The reactivity of these sera with HEp-2 cells was studied using an indirect immunofluorescence assay with and without prior digestion by a DNase, Aspergillus nuclease and the restriction endonucleases Bam HI, Hind III, and Eco RI. CENP-B was purified using affinity chromatography and anti-CENP-B antibody. The interaction between CENP-B and the CENP-B box was evaluated using immunoprecipitation. Precipitates containing alphaDNA were amplified using a PCR method with specific primers for the CENP-B box. RESULTS: None of the nucleases altered the fluorescence pattern. PCR amplification showed that CENP-B adsorbed on a Sepharose-4B/anti-CENP-B antibody column retained alphaDNA satellites. No retention was seen in the absence of CENP-B. CONCLUSIONS: CENP-B protects alphaDNA from digestion by nucleases and prevents DNase or restriction enzyme digestion from affecting the morphology and location of centromeres. CENP-B may promote and maintain joining of DNA satellites in the centromere.

Absence of ANCA in Mexican patients with Takayasu's arteritis.

Antineutrophil cytoplasmic autoantibodies (ANCA) were sought in 43 sera from 39 Mexican patients with typical Takayasu's arteritis (TA), (5 with active and 34 with inactive disease), and in a comparative group comprising 50 sera. Results were negative in all cases. This suggests that ANCA are not a serologic feature in TA per se, even during its active stage. ANCA positivity in TA, when present, may be a non-related phenomenon and probably identifies a subset of patients with atypical forms of TA or a polyangiitis overlap syndrome.