RESUMO

The mitochondrial permeability transition pore (mPTP) opening is involved in the pathophysiology of multiple cardiac diseases, such as ischemia/reperfusion injury and heart failure. A growing number of evidence provided by proteomic screening techniques has demonstrated the role of post-translational modifications (PTMs) in several key components of the pore in response to changes in the extra/intracellular environment and bioenergetic demand. This could lead to a fine, complex regulatory mechanism that, under pathological conditions, can shift the state of mitochondrial functions and, thus, the cell's fate. Understanding the complex relationship between these PTMs is still under investigation and can provide new, promising therapeutic targets and treatment approaches. This review, using a systematic review of the literature, presents the current knowledge on PTMs of the mPTP and their role in health and cardiac disease.

Assuntos

RESUMO

A large number of cannabinoids have been discovered that could play a role in mitigating cardiac affections. However, none of them has been as widely studied as cannabidiol (CBD), most likely because, individually, the others offer only partial effects or can activate potential harmful pathways. In this regard, CBD has proven to be of great value as a cardioprotective agent since it is a potent antioxidant and anti-inflammatory molecule. Thus, we conducted a review to condensate the currently available knowledge on CBD as a therapy for different experimental models of cardiomyopathies and heart failure to detect the molecular pathways involved in cardiac protection. CBD therapy can greatly limit the production of oxygen/nitrogen reactive species, thereby limiting cellular damage, protecting mitochondria, avoiding caspase activation, and regulating ionic homeostasis. Hence, it can affect myocardial contraction by restricting the activation of inflammatory pathways and cytokine secretion, lowering tissular infiltration by immune cells, and reducing the area of infarct and fibrosis formation. These effects are mediated by the activation or inhibition of different receptors and target molecules of the endocannabinoid system. In the final part of this review, we explore the current state of CBD in clinical trials as a treatment for cardiovascular diseases and provide evidence of its potential benefits in humans.

Assuntos

RESUMO

Background and objective Acute transverse myelitis (TM) is an infrequent neurological complication of systemic lupus erythematosus (SLE). Short-term outcome varies widely between cohorts. Little is known about the epidemiology and long-term functional outcome of TM associated to SLE. Methods Patients with SLE and acute TM were identified during hospital admission, visits to the Emergency Room or the Neurology Outpatient Clinic. We evaluated ambispectively those patients with SLE presenting with clinical myelopathy and corroborated with spinal MRI. Cases were divided as partial (non-paralyzing) or complete (paralyzing). We determined long-term functional outcome as well as mortality in those patients with follow-up periods of at least five years. Results We identified 35 patients (partial, n = 15; complete, n = 20) in which complete clinical and imaging data were available (26 with follow-up ≥ 5 years). Patients with complete TM were significantly older than those with partial forms. Positive antiphospholipid antibodies were observed in 80% of patients, suggesting a possible mechanistical role. Surprisingly, functional recovery at one year was in general good; however, we observed a five-year mortality of 31% because of sepsis (in 10 cases) or pulmonary embolism (in one case). Conclusions Short-term outcome of SLE-related TM is generally good, and recurrence rate is low. However, we observed a long-term fatality rate of 31% for reasons unrelated to TM, suggesting that TM is a manifestation of severe immune dysregulation and a predictor of severity and mortality in patients with SLE.

Assuntos

RESUMO

Protein corona (PC) is the main biological entity of initial cell interaction and can define the toxicological response to Fe3O4 nanoparticles (IONP). Polymer coating to IONP, polyethilenglycol (PEG) and polyvinylpyrrolidone (PVP), is a widely accepted strategy to prevent toxicity and avoid excessive protein binding. The aim of this study was to assess the role of PC as a potential protector for ROS-induced cytotoxicity and pro-inflammatory response in THP-1 macrophages (exposed to three different IONP: bare, PVP or PEG coated). Cells were exposed to either IONP in RPMI-1640 media or IONP with a preformed human PC. All three IONP showed cytotoxic effects, which in the presence of PC was abolished. IONP-PEG exposure significantly increased ROS, mitochondrial dysfunction and pro-inflammatory cytokines release (IL-1ß and TNF-α). PC presence on IONP-PEG promoted a decrease in ROS and prevented cytokine secretion. Also, presence of PC reduced cell uptake for IONP-bare, but had no influence on IONP-PVP or IONP-PEG. Hence, the reduction in IONP-PEG cytotoxicity can be attributed to PC shielding against ROS generation and pro-inflammatory response and not a differential uptake in THP-1 macrophages. The presence of the PC as a structural element of NP biological entity provides in vivo-relevant conditions for nanosafety testing.

Assuntos

Assuntos

RESUMO

The urinary steroid profile has been used in clinical endocrinology for the early detection of enzyme deficiencies. In the field of doping, its evaluation in urine samples is used to diagnose the abuse of substances prohibited in sport. This profile is influenced by sex, age, exercise, diet, and ethnicity, among others; laboratories own reference ranges might compensate for ethnic differences among population and inter-laboratory biases. This paper shows the reference ranges obtained in the Antidoping Laboratory of Havana for the following steroid profile parameters: ten androgens (testosterone, epitestosterone, androsterone, etiocholanolone, 5α-androstan-3α,17ß-diol, 5ß-androstan-3α,17ß-diol, dehydroepiandrosterone, epiandrosterone, 11ß-hydroxyandrosterone and 11ß-hydroxyetiocholanolone), three estrogens (estradiol, estriol and estrone), two pregnanes (pregnanediol and pregnanetriol) and two corticosteroids (cortisol and tetrahydrocortisol). The urine samples (male: n = 2454 and female: n = 1181) and data obtained are representative of population from Latin-American countries like Cuba, Venezuela, Mexico, Dominican Republic, Guatemala and Chile. Urine samples were prepared by solid-phase extraction followed by enzymatic hydrolysis and liquid-liquid extraction with an organic solvent in basic conditions. Trimethylsilyl derivatives were analyzed by gas chromatography coupled to mass spectrometry. Reference ranges were established for each sex, allowing the determination of abnormal profiles as a first diagnostic tool for the detection of the abuse of androgenic anabolic steroids. The comparison with the Caucasian population confirms that the urinary steroid profile is influenced by ethnicity.

Assuntos

RESUMO

Calcipotriol is an analogue of vitamin D3 with effect on epidermal keratinization, cellular division and modulation of immune response. An evaluation of its therapeutic effect when given in twenty-five psoriatic patient with less than 25% of their body surface affected was done. The medication was applied twice daily during six weeks on involved areas. The evolution was evaluated by the psoriatic area and severity index (PASI) analysis. The evaluation of initial and terminal PASI analysis revealed a decrease in the psoriatic activity that fluctuated from 25% to 100%, with a 61% average. A reactivation in the psoriatic lesion was noticed two weeks after the medication was halted; thereafter, the calcipotriol was restarted for an additional four weeks and a decrease in their PASI with a 74% average was achieved. There were no important side effects reported. Calcipotriol is effective in the treatment of psoriasis and it is an important addition to the therapeutic medications available to treat psoriasis. It is important to give the treatment for longer periods of time for evaluating the possibility to induce prolonged remissions.

Assuntos

RESUMO

Seventy one patients with abnormal cervical cytology, were submitted to electrosurgical resection of the transformation zone, as part of diagnostic and therapeutic protocol. The resection was done at the office, on ambulatory basis and with local anesthesia with an average of 10 for its realization. The obtained specimen was 2 x 2 cm in area, and depth of one cm. Morbidity was 9.8%, and considered lesser. Only 2.8% required hospitalization. Procedure acceptability by the patient was more than 95%. It is concluded that it offers diagnostic precision with a technique easily done, and that it may be a therapeutic alternative.

Assuntos

RESUMO

The polymerase chain reaction was used to amplify DNA sequences of the etiologic agent of Lyme disease, Borrelia burgdorferi, and was applied to the detection of the spirochete in humans and dogs. Oligonucleotide primers used in the reaction flank a 244-base-pair representing part of the variable region V4 of the B. burgdorferi 16S rRNA from biopsies of patients with acrodermatitis, and in synovial fluid from a dog with arthritis. These data suggest the presence of the disease in our state.

Assuntos

RESUMO

We report the excellent therapeutic response of actinomycetoma treated with amikacin-trimethoprim-sulfamethoxazole. The medication was given in cycles for 5 weeks. Ninety-five percent of all cases were cured after 5, 10 or 15 weeks treatment.

Assuntos

RESUMO

Several lines of evidence have clearly established the role of lipoproteins as risk factors for the development of atherosclerosis. Epidemiologic studies from different countries have found that about one third of myocardial infarction survivors under 60 years of age are hyperlipidemic. The acute stress reaction occurring in the first hours following an acute myocardial infarction causes distinct changes in the patient's metabolic profile, these changes include a significant reduction of total cholesterol and cholesterol associated with low density lipoproteins and a usually mild elevation of blood glucose. With the purpose of establishing the prevalence and severity of lipoprotein disorders found in myocardial infarction survivors living in Mexico city we conducted a prospective study of 106 consecutive admissions to the coronary care unit at the National Institute of Cardiology with the fully proven diagnosis of acute myocardial infarction, we included only patients younger than 60 years of age that could be sampled within the first 72 hours of the appearance of typical symptoms, at this time the coronary risk factor profile was assessed and blood samples were drawn (acute sample). After three months of the diagnosis we sampled 81 of the original 106 patients (chronic sample). The comparison of these 81 patients showed remarkable differences in the lipid values obtained on each sample. The mean value for total cholesterol in the acute sample was 225 mg/dl whereas the corresponding value for the chronic sample was 240.5 mg/dl (p less than 0.005). This difference was also highly significant for the low density fraction. On the basis of the chronic sample analysis we estimated a prevalence of hyperlipoproteinemia of 35.8%. (II: 18.5%, III: 2.5%, IV: 14.8%), an additional subgroup of 10 patients (12.3%) had the hypo-HDL phenotype raising the number of subjects at risk for atherosclerosis to as high as 48.1% considering only the lipoproteins. The prevalence figures for the rest of the risk factors were as follows: 70.3% for tobacco smoking, 35.8% for Systemic Arterial Hypertension, 33.4% for Obesity and 30.8% for Diabetes Mellitus. Among the group of 81 patients, 17 were known diabetics, eight additional cases of Diabetes Mellitus were diagnosed at the chronic phase (two with fasting hyperglycemia and six with diagnostic oral glucose tolerance tests). The "acute plase" glycemia for these eight subjects was significantly higher (mean: 98.4 mg/dl) than the corresponding value for the non diabetic patients (mean: 83.4 mg/dl p less than 0.002), the seventeen known diabetics had a mean glycemia of 150.6 mg/dl in the acute sample.(ABSTRACT TRUNCATED AT 400 WORDS)

Assuntos

RESUMO

The overall prevalences of microvascular complications and their association with dietary, clinical, and metabolic characteristics have been studied in 503 Mexican type II diabetic subjects. Average daily dietary intakes were 1866 kcal, 46.5% as carbohydrate, 13.7 mmol cholesterol, 8.7 g fiber, and a polyunsaturated/saturated fat ratio of 0.98. Prevalence rates of microvascular and metabolic complications were as follows: background retinopathy 12.3%, exudative retinopathy 24.2%, proliferative retinopathy 8.1% (1% blind, 4% able to read large print only), 9.1% of patients had cataract, 15.9% nephropathy, and 40.8% peripheral neuropathy. In addition, 3.6% had experienced transient lower motor neuron facial paralysis and 0.2% oculomotor paralysis. Patients with retinopathy had a longer mean duration of diabetes, were less obese at the time of examination, and had higher initial and mean blood pressures and higher mean fasting blood glucose levels when compared with those without retinopathy. Similar differences were observed between groups with and without nephropathy except that mean blood glucose levels were similar in the two groups. The presence of peripheral neuropathy was associated with longer duration of diabetes, less obesity, higher mean blood pressure and mean blood glucose levels, and lower hemoglobin concentration. Patients treated with diet alone had significantly lower prevalences of all three microvascular complications but they also had significantly shorter duration of diabetes and lower mean blood glucose levels. However, multivariate analyses on the subgroup of 360 patients who had repeated fasting blood glucose measurements for at least 5 yr demonstrated associations between retinopathy and duration of diabetes, mean blood pressure and mean blood glucose, and percent calories from carbohydrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Assuntos

RESUMO

Macrovascular and microvascular complications of diabetes may be associated with different environmental factors. To investigate this further, a prevalence study of 503 Mexican type II diabetic subjects was carried out while their patterns of nutrition were constrained by government food subsidies. Average daily dietary intakes were 1866 kcal; 46.5% as carbohydrate, 13.7 mmol cholesterol, 8.7 g fiber, and a polyunsaturated/saturated fat ratio of 0.98. With respect to macrovascular disease, 49.3% of patients had evidence of peripheral vascular disease, and 21.6% myocardial ischemia, 6.0% angina, 10.8% EKG evidence of ischemia, 4.8% EKG evidence of myocardial infarction. Only 1.2% (six patients) had a clear history of completed stroke, and all were hypertensive. Six patients had also undergone amputations for diabetic gangrene. Tabulation of the means of clinical characteristics according to presence or absence of myocardial ischemia showed that higher cholesterol, calorie, and fat intake, higher mean blood pressure, higher serum cholesterol, and serum triglyceride levels were found in those with myocardial ischemia. Patients with peripheral vascular disease were more commonly smokers. Stepwise logistic regression revealed significant positive associations between myocardial ischemia and dietary cholesterol, serum cholesterol, and mean blood pressure. In contrast, the presence of peripheral vascular disease was significantly related only to smoking and retinopathy. There were no associations between macrovascular complications and duration of diabetes in the multivariate analysis, and they occurred with equal frequency in men and women. Prospective studies of atherosclerosis in maturity-onset diabetes should assess and seek to modify dietary cholesterol, serum cholesterol, and hypertension.

Assuntos

RESUMO

PIP: The results obtained in 285 cases of tubal occlusion by laparoscopic electrofulguration, are presented. Surgical and anesthetic techniques were analyzed, as well as laparoscopic findings, the time used for the procedure, complications, and the time that the patients needed to go back to their usual activities. It is concluded that although there are safer and more harmless methods (and even with recannalization possibilities), the procedure is useful for the purpose. It is especially convenient for large groups of population because of its low cost. (Author's modified)^ieng

Assuntos

Assuntos

RESUMO

Approximately 20 thousand bovines of autochtonious and imported breeds, located in different regions of the Country were serologically tested by Immuno-diffusion (I.D.) in agar, using BLV GP60 antigens, for the purpose of determining the prevalence of infection by Bovine Leukemia Virus. Hematologic and histopathologic assays were made with the object of determining variations in hematologic values and the determination of stages of persistent lymphocytosis, and of studying the morphocytological changes that accompany malignant transformations of lymphoid elements, in order to make studies on the incidence of clear tumoral lesions in herds highly affected by Leukemia. From 16 thousand samples of serum, tested by the I.D., 6 thousand were positives (37,5%) pertaining to 150 herds distributed in all 20 states of the Country. The sera correspond to different breeds: dairy cattle, beef cattle, brahman, zebú hybrids, and buffalo. Hematologically, persistent lymphocytosis induced by the BLV was verified, by previously discarding other pathologic stages with transitory lymphocytosis. Factors which explain this high incidence and the spread of the Bovine Leukemia in Venezuela were detected.

Assuntos

Assuntos

Assuntos

Assuntos