Role of MicroRNAs in Signaling Pathways Associated with the Pathogenesis of Idiopathic Pulmonary Fibrosis: A Focus on Epithelial-Mesenchymal Transition.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with high mortality and unclear etiology. Previous evidence supports that the origin of this disease is associated with epigenetic alterations, age, and environmental factors. IPF initiates with chronic epithelial lung injuries, followed by basal membrane destruction, which promotes the activation of myofibroblasts and excessive synthesis of extracellular matrix (ECM) proteins, as well as epithelial-mesenchymal transition (EMT). Due to miRNAs' role as regulators of apoptosis, proliferation, differentiation, and cell-cell interaction processes, some studies have involved miRNAs in the biogenesis and progression of IPF. In this context, the analysis and discussion of the probable association of miRNAs with the signaling pathways involved in the development of IPF would improve our knowledge of the associated molecular mechanisms, thereby facilitating its evaluation as a therapeutic target for this severe lung disease. In this work, the most recent publications evaluating the role of miRNAs as regulators or activators of signal pathways associated with the pathogenesis of IPF were analyzed. The search in Pubmed was made using the following terms: "miRNAs and idiopathic pulmonary fibrosis (IPF)"; "miRNAs and IPF and signaling pathways (SP)"; and "miRNAs and IPF and SP and IPF pathogenesis". Additionally, we focus mainly on those works where the signaling pathways involved with EMT, fibroblast differentiation, and synthesis of ECM components were assessed. Finally, the importance and significance of miRNAs as potential therapeutic or diagnostic tools for the treatment of IPF are discussed.

Exosomal Micro-RNAs as Intercellular Communicators in Idiopathic Pulmonary Fibrosis.

Communication between neighboring or distant cells is made through a complex network that includes extracellular vesicles (EVs). Exosomes, which are a subgroup of EVs, are released from most cell types and have been found in biological fluids such as urine, plasma, and airway secretions like bronchoalveolar lavage (BAL), nasal lavage, saliva, and sputum. Mainly, the cargo exosomes are enriched with mRNAs and microRNAs (miRNAs), which can be transferred to a recipient cell consequently modifying and redirecting its biological function. The effects of miRNAs derive from their role as gene expression regulators by repressing or degrading their target mRNAs. Nowadays, various types of research are focused on evaluating the potential of exosomal miRNAs as biomarkers for the prognosis and diagnosis of different pathologies. Nevertheless, there are few reports on their role in the pathophysiology of idiopathic pulmonary fibrosis (IPF), a chronic lung disease characterized by progressive lung scarring with no cure. In this review, we focus on the role and effect of exosomal miRNAs as intercellular communicators in the onset and progression of IPF, as well as discussing their potential utility as therapeutic agents for the treatment of this disease.

Glycine supplementation during six months does not alter insulin, glucose or triglyceride plasma levels in healthy rats.

Nowadays, glycine is used in nutritional supplements and to attenuate chronic complications of diabetes and obesity; however, its use has side effects as insulin resistance. Our aim was to evaluate the effect of chronic glycine supplementation on insulin, glucose and triglyceride levels in healthy Wistar rats. Groups were: Control (C), that received sterilized water only, glycine (GG), that received 1% glycine and taurine (TG), that received 0.5% taurine during 6 months (n = 10). Our results showed no differences in plasma insulin levels after six months of supplementation (C: 13.22 ± 2.0; GG: 11.4 ± 2.0; TG: 11.13 ± 2.0 ng/ml; p = 0.64). Likewise, neither glucose plasma concentration (C: 99.9 ± 3.9 mg/dl; GG: 104.3 ± 4.3 mg/dl; TG: 104.5 ± 4.8 mg/dl) (p = 0.88) nor triglyceride levels (C: 58.4 ± 5.6 mg/dl; GG: 46.9 ± 2.3 mg/dl; TG: 50.68 ± 3.3 mg/dl), showed differences after six months supplementation (p = 0.22). Furthermore, the analysis of glycine (C: 80 ± 24.6; GG: 83.9 ± 25.9; TG: 90.7 ± 13.5 nmol/ml) (p = 0.19) and taurine (C: 169 ± 15.17; GG: 148.7 ± 23.9; TG: 165.8 ± 22.5 nmol/ml) (p = 0.4) in the plasma of animals with supplementation showed no significant changes. Additionally, general urine tests and histological analysis of liver or kidneys showed no alterations. In conclusion, chronic supplementation with 1% glycine did not have any significant detrimental side effects in our model. However, more studies are still necessary to evaluate the effect of 1% glycine supplementation in humans.

Thiamine pyrophosphate diminishes nitric oxide synthesis in endothelial cells.

Although thiamine pyrophosphate (TPP) is considered a protective agent for endothelial cells, it is still unknown if this is associated with nitric oxide (NO) synthesis. Our aim was to evaluate the synthesis of NO in endothelial cells incubated with TPP and high glucose concentrations. Endothelial cells from the umbilical cord vein from newborns (n = 20), were incubated with 5, 15 or 30 mmol/L glucose, in absence or presence of 0.625 mg/ml of TPP. Our results showed a significant increase in cell proliferation (> 40%; P < 0.05), and cell viability (> 90%; P < 0.001) after 48 h in endothelial cells cultured with glucose plus TPP. Likewise, in the presence of glucose and TPP an important rise in the consumption of glucose by the endothelial cells was observed after 24 h (> 7%; P < 0.001) and 48 h (> 10%; P < 0.05). Additionally, the levels of lactate after incubation with glucose and TPP showed only slight variations after 48 h (P < 0.05). However, these changes were clearly different from those observed in the absence of TPP. Interestingly, we found that the changes mentioned were linked with reduced levels of nitrites both at 24 h (< 171 pmol/µg protein; P < 0.001), and 48 h (< 250 pmol/µg protein; P < 0.05), which was associated with a reduced expression of mRNA of eNOS in endothelial cells incubated with TPP and high glucose. In conclusion, the presence of TPP regulates the consumption of glucose and the synthesis of NO, which would explain its protective effect in the endothelium of diabetic patients.

Prevalence and risk factors to Demodex folliculorum infection in eyelash follicles from a university population of Mexico.

Demodex folliculorum shows a high occurrence in the general population, however, its pathologic relevance is still controversial. In this prospective study, we evaluated the prevalence of D. folliculorum on eyelashes from 8,033 subjects of a university population (including 7,782 students, and 251 academics). Additional information on some risk factors to infection by the mites was evaluated, as well. A prevalence of 1.47% was found, where 118 individuals were positive for D. folliculorum; and, among them, 63 (53.4%) were women and 55 (46.6%) were men. Results showed a negative correlation with the age (r = -0.45), the highest prevalence was found in individuals between 19 and 22 years of age (2.1%, 84 patients). The number of D. folliculorum mites did not differ between the right and left eye; however, the use of cosmetics or facial cream, contact lens, hair removers, were factors present in patients infected with D. folliculorum. Although Demodex prevalence did not increase in line with weight, we found significantly higher prevalence in the 51-60 kg and 71-80 kg weight groups, and a particularly high prevalence in the over 81 kg weight group (2.6%). In conclusion, it was observed that the main population positive to infection consisted of young adults; this is in contrast with the international evidence reporting a high rate of infection in older adults. Besides, our results suggest that items of daily use such as cosmetics, facial cream, eyeliner, glasses, or contact lenses may be some of the main culprits of the infection by D. folliculorum.

High mortality associated with hyperglycemia, neutrophilia, and lymphopenia in critically ill patients.

A common finding in patients admitted to an Intensive Care Unit (ICU) is hyperglycemia without prior history of diabetes. This increase in blood glucose is considered a negative prognostic factor for patients in the ICU. Hence, we performed a retrospective cohort study in patients admitted at the ICU of the National Institute of Respiratory Diseases (INER) in a 7-month period; we collected data about their blood glucose concentration during their stay at the ICU. We gathered the available medical records of 30 patients out of 58 admitted to the ICU. Among the 30 patients, 21 patients survived (70%) and 9 patients with community-acquired pneumonia (CAP) died (30%). The 21 surviving patients included 17 patients with acute respiratory distress secondary to CAP and 4 patients with asthmatic crisis upon admission to the ICU. After admission, all patients progressed to sepsis and showed an increase in blood glucose. We detected higher glucose concentrations in deceased patients (147 mg/dl ± 4.23), as compared to surviving patients (129 mg/dl ± 2.17) (P < 0.001). In addition, the percentage of lymphocytes was lower in deceased patients than that in surviving patients (5.7 vs. 11.8%, P < 0.001), whereas percentage of neutrophils was elevated in the deceased patients (90.7 vs. 80.9%, P < 0.001). It is therefore important to measure continuously glucose concentrations, as well as the numbers of neutrophils and lymphocytes in critically ill patients with hyperglycemia. Such a simple monitoring plan may prevent fatal complications in patients admitted to ICU.

Galectin-10 is released in the nasal lavage fluid of patients with aspirin-sensitive respiratory disease.

The aim of this work was to determine the presence of galectin-10 in nasal lavage fluid (NLF) of patients with aspirin-sensitive respiratory disease (ASRD) before and after challenge with L-ASA (aspirin) by ELISA. Fifteen ASRD patients, ten aspirin-tolerant asthmatics (ATA), and fifteen healthy controls (HC) were studied. The baseline presence of Galectin-10 in PBMC was determined using real time PCR. Galectin-10 was evaluated in tissue of nasal polyps by western blot. Our results showed a lower expression in PBMC of ASRD patients than in ATA and healthy controls. However, a higher concentration of galectin-10 in NLF was found in ASRD patients before and after L-ASA challenge; western blot confirmed a high expression of galectin-10 in tissue from nasal polyps obtained from ASRD patients. Our results suggest a probable role of galectin-10 in the inflammatory response observed in ASRD patients; however, confirmatory studies are needed.

Antihyperalgesic and Antiallodynic Effects of Amarisolide A and Salvia amarissima Ortega in Experimental Fibromyalgia-Type Pain.

Salvia amarissima Ortega is an endemic species of Mexico used in folk medicine to alleviate pain and as a nervous tranquilizer. The S. amarissima extract and one of its abundant metabolites, identified and isolated through chromatographic techniques, were investigated to obtain scientific evidence of its potential effects to relieve nociplastic pain such as fibromyalgia. Then, the extract and amarisolide A (3-300 mg/kg, i.p.) were pharmacologically evaluated in reserpine-induced fibromyalgia-type chronic pain and in depressive-like behavior (as a common comorbidity) by using the forced swimming test in rats. The 5-HT1A serotonin receptor (selective antagonist WAY100635, 1 mg/kg, i.p.) was explored after the prediction of a chemical interaction using in silico analysis to look for a possible mechanism of action of amarisolide A. Both the extract and amarisolide A produced significant and dose-dependent antihyperalgesic and antiallodynic effects in rats, as well as significant antidepressive behavior without sedative effects when the antinociceptive dosages were used. The 5-HT1A serotonin receptor participation was predicted by the in silico descriptors and was corroborated in the presence of WAY100635. In conclusion, S. amarissima possesses antihyperalgesic, antiallodynic, and anti-depressive activities, partially due to the presence of amarisolide A, which involves the 5-HT1A serotonin receptor. This pharmacological evidence suggests that S. amarissima and amarisolide A are both potential alternatives to relieve pain-like fibromyalgia.

Risk of Pulmonary Fibrosis and Persistent Symptoms Post-COVID-19 in a Cohort of Outpatient Health Workers.

Background: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. Methods: A longitudinal prospective study on health workers infected by SARS-CoV-2 was conducted. In this work, signs and symptoms were recorded of 149 health workers with a positive PCR test for SARS-CoV-2 at the beginning of the diagnosis, during the active infection, and during post-COVID-19 follow-up. The McNemar chi-square test was used to compare the proportions and percentages of symptoms between the baseline and each follow-up period. Results: The signs and symptoms after follow-up were cardiorespiratory, neurological, and inflammatory. Gastrointestinal symptoms were unusual at the disease onset, but unexpectedly, their frequency was higher in the post-infection stage. The multivariate analysis showed that pneumonia (HR 2.4, IC95%: 1.5−3.8, p < 0.001) and positive PCR tests still after four weeks (HR 5.3, IC95%: 2.3-12.3, p < 0.001) were factors associated with the diagnosis of post-COVID-19 pulmonary fibrosis in this study group. Conclusions: Our results showed that pneumonia and virus infection persistence were risk factors for developing pulmonary fibrosis post-COVID-19, after months of initial infection.

Ivermectin: A Controversial Focal Point during the COVID-19 Pandemic.

The SARS-CoV-2 pandemic has confirmed the apocalyptic predictions that virologists have been making for several decades. The challenge the world is facing is that of trying to find a possible treatment, and a viable and expedient option for addressing this challenge is the repurposing of drugs. However, in some cases, although these drugs are approved for use in humans, the mechanisms of action involved are unknown. In this sense, to justify its therapeutic application to a new disease, it is ideal, but not necessary, to know the basic mechanisms of action involved in a drug's biological effects. This review compiled the available information regarding the various effects attributed to Ivermectin. The controversy over its use for the treatment of COVID-19 is demonstrated by this report that considers the proposal unfeasible because the therapeutic doses proposed to achieve this effect cannot be achieved. However, due to the urgent need to find a treatment, an exhaustive and impartial review is necessary in order to integrate the knowledge that exists, to date, of the possible mechanisms through which the treatment may be helpful in defining safe doses and schedules of Ivermectin.

Could a family history of type 2 diabetes be a risk factor to the endothelial damage in the patient with COVID-19?

In December 2019, in China, a disease derived from a new beta coronavirus (SARS-CoV-2) was reported, which was termed coronavirus disease 2019 (COVID-19). Currently, it is known that endothelial cell dysfunction is a critical event in the infection by this virus. However, in a representative percentage of patients with COVID-19, neither cardiovascular disease nor diabetes mellitus, which could be linked with endothelial dysfunction, has been reported. Previous evidence has shown the presence of early endothelial dysfunction in healthy subjects but with a family history of type 2 diabetes (FH-DM2), where glucose metabolism, the synthesis of nitric oxide (NO), reactive oxygen species (ROS), as well as expression of genes involved with their synthesis are impaired. Besides, in subjects with an FH-DM2, the presence of hyperinsulinemia and high glucose levels are common events that could favor the infection of endothelial cells by the coronavirus. Interestingly, both events have been reported in patients with COVID-19, in whom hyperinsulinemia increases the surface expression of ACE2 through a diminution of ADAMTS17 activity; whereas hyperglycemia induces higher expression of ACE2 in different tissues, including microvascular endothelial cells from the pancreatic islets, favoring chronic hyperglycemia and affecting the release of insulin. Therefore, we hypothesized that an FH-DM2 should be considered an important risk factor, since the individuals with this background develop an early endothelial dysfunction, which would increase the susceptibility and severity of infection and damage to the endothelium, in the patient infected with the SARS-CoV-2.

Evaluating of Red Blood Cell Distribution Width, Comorbidities and Electrocardiographic Ratios as Predictors of Prognosis in Patients with Pulmonary Hypertension.

Pulmonary hypertension is a rare condition that impairs patients' quality of life and life expectancy. The development of noninvasive instruments may help elucidate the prognosis of this cardiorespiratory disease. We aimed to evaluate the utility of routinely performed noninvasive test results as prognostic markers in patients with pulmonary hypertension. We enrolled 198 patients with mean pulmonary artery pressure >25 mmHg measured at cardiac catheterisation or echocardiographic pulmonary artery systolic pressure > 40 mmHg and tricuspid regurgitation Vmax >2.9 m/s, and clinical information regarding management and follow-up studies from the date of diagnosis. Multivariate analysis revealed that female sex [HR: 0.21, (95% CI: 0.07-0.64); p = 0.006], the presence of collagenopathies [HR: 8.63, (95% CI: 2.38-31.32); p = 0.001], an increased red blood cell distribution width [HR: 1.25, (95% CI: 1.04-1.49); p = 0.017] and an increased electrocardiographic P axis (P°)/T axis (T°) ratio [HR: 0.93, (95% CI: 0.88-0.98); p = 0.009] were severity-associated factors, while older age [HR: 1.57, (95% CI: 1.04-1.28); p = 0.006], an increased QRS axis (QRS°)/T° ratio [HR: 1.21, (95% CI: 1.09-1.34); p < 0.001], forced expiratory volume in 1 s [HR: 0.94, (95% CI: 0.91-0.98); p = 0.01] and haematocrit [HR: 0.93, (95% CI: 0.87-0.99); p = 0.04] were mortality-associated factors. Our results support the importance of red blood cell distribution width, electrocardiographic ratios and collagenopathies for assessing pulmonary hypertension prognosis.

Ultrastructural changes and immunolocalization of P-selectin in platelets from patients with major depression.

Depression is considered an important risk factor in patients with cardiovascular disease (CVD). Although the biological mechanism is unknown, it has been suggested that hyperactivity of platelets may have an important role in the onset and evolution of cardiovascular damage. The goals of this study were to evaluate by transmission electron microscopy and immunohistochemistry the presence of ultra-structural variations in platelets from individuals with recent diagnosis of major depression disease (MDD, patients without previous anti-depressant treatment and from healthy control subjects.). Platelets from depressed patients had a greater proportion of dendritic forms compared with those obtained from control subjects. Morphological changes, such as dilation of open canalicular and dense tubular systems, platelet vacuolization, electrodense pattern of membranes, and a different immunolocalization of P-selectin were observed in the platelets from depressed patients compared with those isolated from healthy subjects. Our results revealed ultra-structural changes in platelets isolated from patients with MDD suggestive of enhanced platelet activation.

An association between glycine and insulin levels is observed in patients with pulmonary tuberculosis and type 2 diabetes.

BACKGROUND & AIMS: Adequate nutrition from which amino acids are part gives us protection against infectious or metabolic diseases. In particular, glycine has immunomodulatory properties and is a secretagogue of insulin. However, its absorption rate or plasma levels are impaired in bacterial infection or high glucose levels. The aim of this study was to evaluate the association between glycine and insulin plasma levels in patients with pulmonary tuberculosis (PTB) and type 2 diabetes mellitus (DM2). METHODS: Plasma levels of insulin and glycine were determined in four groups: 1) patients with PTB; 2) patients with PTB-DM2; 3) household contacts with DM2 (C-DM2), and 4) healthy household contacts (H-C). Likewise, we analyzed the plasma levels of glucose, serine, arginine, lysine, taurine, and glutamic acid. RESULTS: We observed significant differences in the glycine levels between PTB and PTB-DM2 vs C-DM2 and H-C groups (P < 0.05). We observed also important differences in insulin and glucose levels after comparisons between PTB, PTB-DM2, and C-DM2 vs. H-C groups (P < 0.05). A correlation between glycine and insulin levels in the PTB (r = 0.326) and PTB-DM2 (r = 0.318) groups was found. CONCLUSION: Our results showed a significant association between glycine and insulin plasma levels in patients with PTB and PTB-DM2, which suggests that the determination of glycine levels could be used as a reference test to evaluate both pathologic conditions. An additional support to the above is that significant changes in the glucose levels in these groups were observed, too.

Incubation with DNase I inhibits tumor cell proliferation.

BACKGROUND: Deoxyribonuclease I (DNase-I) plays an important role in the elimination of damaged-, aging- or cancer cells. Various authors suggest that programmed cell death (PCD) is attenuated in cancer cells due to a reduced activity of DNase-I. MATERIAL AND METHODS: In this work, we evaluated cell viability (violet crystal stain), cell proliferation (tritiated thymidine) and DNA degradation of tumoral cells (Calu-1, SK-MES-1, HeLa, HEp-2, L-929) incubated with different concentrations of DNase I. PBMN cells and human fetal fibroblasts served as controls. RESULTS: Our results showed a >90% decrease in the viability of HeLa and HEp-2 cells, and >50%<90% decline in Calu-1, SK-MES-1 and L-929 cell viability, incubated with 9 mg/ml of DNase-I in comparison with control cells (p<0.05). The incorporation of [3H]thymidine showed a 50% decrease in tumoral cells. Control cells showed no significant differences. Tumor cell DNA degradation was observed after nuclease treatment, however the typical DNA ladder, characteristic of the apoptotic cell, was not observed. The morphology of some DNAse-I treated tumor cells suggested autoschizis CONCLUSION: Our results suggest that the use of a DNA nuclease might have some benefits in the treatment of cancer since it inhibits cell growth, probably by inducing autoschizis.

The interaction between Histoplasma capsulatum cell wall carbohydrates and host components: relevance in the immunomodulatory role of histoplasmosis.

Histoplasma capsulatum is an intracellular fungal pathogen that causes respiratory and systemic disease by proliferating within phagocytic cells. The binding of H. capsulatum to phagocytes may be mediated by the pathogen's cell wall carbohydrates, glucans, which consist of glucose homo and hetero-polymers and whose glycosydic linkage types differ between the yeast and mycelial phases. The alpha-1,3-glucan is considered relevant for H. capsulatum virulence, whereas the beta-1,3-glucan is antigenic and participates in the modulation of the host immune response. H. capsulatum cell wall components with lectin-like activity seem to interact with the host cell surface, while host membrane lectin-like receptors can recognize a particular fungal carbohydrate ligand. This review emphasizes the relevance of the main H. capsulatum and host carbohydrate-driven interactions that allow for binding and internalization of the fungal cell into phagocytes and its subsequent avoidance of intracellular elimination.

Central and peripheral anti-hyperalgesic effects of diosmin in a neuropathic pain model in rats.

Flavonoids are natural compounds showing anti-hyperalgesic activity in models of pain. Diosmin is a compound poorly studied in the treatment of neuropathic pain. This study evaluates the anti-hyperalgesic actions of diosmin and possible mechanisms of action involved by using a neuropathic pain model in rats. Experimental neuropathic pain was induced by chronic constriction injury (CCI) in male Wistar rats, then aesthesiometric index and plantar tests were assessed to evaluate mechanical and thermal hyperalgesia, respectively, in order to explore the analgesic effects of acute and sub-chronic treatment with diosmin. The GABAA, 5-HT1A, D2-like and opioid receptors participation, as well as levels of TNF-α, IL-1ß and IL-6, were evaluated in the spinal cord and sciatic nerve tissues after acute and subchronic diosmin administration. In addition, the presence of diosmin on cerebral samples was determined by UHPLC-MS analysis. Acute and sub-chronic treatment with diosmin significantly diminished the mechanical and thermal hyperalgesia induced by CCI in rats. This anti-hyperalgesic effects of diosmin were modified in the presence of naloxone (1mg/kg, i.p.) and haloperidol (0.1mg/kg, i.p.), but not by GABAA and 5-HT1A receptor antagonists. The anti-hyperalgesic effects of diosmin were also linked with reduced levels of TNF-α, IL-1ß and IL-6. The presence of diosmin in the cerebral samples was confirmed by chromatographic analysis. In conclusion, our results provide evidence that diosmin produces significant anti-hyperalgesic effects acting at central level by an opioid and D2 dopaminergic receptors participation, and at peripheral level by reducing proinflammatory cytokines.

Association between IL-15 and insulin plasmatic concentrations in patients with pulmonary tuberculosis and type 2 diabetes.

IL-15 is part of the immune response in pulmonary tuberculosis (PTB) but amazingly, it may also induce physiological effects similar to those of insulin. We evaluated the IL-15 and insulin plasmatic levels in adults with PTB and with or without type 2 diabetes mellitus (DM2), who received previous antituberculosis therapy for at least 2 months. We analyzed the concentrations of glucose, glycated hemoglobin, insulin, as well as levels of IL-15, IL-2, IFN-γ, and TNF-α in patients with PTB, patients with PTB-DM2, household contacts with DM2 (C-DM2), and healthy household contacts (H-C). Our results showed unexpected high levels of glucose, insulin, and IL-15 in the PTB and C-DM2 groups. In comparison, low levels of these same indicators were observed in the PTB-DM2 and H-C groups. Interestingly, our analysis showed a positive correlation of IL-15 with insulin in the PTB group (r = 0.73) and in the C-DM2 group (r = 0.66). In comparison, a weak correlation between IL-15 and insulin was observed in the PTB-DM group (r = 0.10) and in the H-C group (ρ = 0.26). Our results suggest an association between IL-15 and insulin levels in the patient with PTB. Intriguingly, this association was weaker in the patient with PTB-DM2.

Hypertriglyceridemia is linked to reduced nitric oxide synthesis in women with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP), which affect 8% to 15% of pregnancies, are associated with nitric oxide dysfunction and hyperlipidemia, but their precise role in HDP remains controversial. In order to gain more insight into the mechanisms underlying HDP, we evaluated some indicators common to the diseases associated with endothelial dysfunction. METHODS: Plasma samples were obtained from 47 normotensive women (control group) and from 27 women with HDP (experimental group). All women were 7 months pregnant. Body mass index as well as triglycerides, nitrite concentrations, total cholesterol, LDL-cholesterol, HDL-cholesterol, glucose, and glycated hemoglobin were determined. RESULTS: Our results showed significant differences in body mass index (30.4 +/- 1.3 vs 28.3 +/- 0.6 kg/m(2), p < 0.05), triglycerides (363 +/- 137 vs. 263 +/- 80 mg/dL, p < 0.01), nitrites (19.6 +/- 5.2 vs. 15.2 +/- 5.0 micromol/L, p < 0.01), and glucose (92 +/- 25 vs. 81 +/- 10.8 mg/dL, p < 0.05) in women from the experimental group compared with the control group. Interestingly, nitric oxide synthesis was significantly reduced when triglycerides and cholesterol concentrations were increased (p < 0.018 and p < 0.002, respectively). Moreover, there was a strong association (odds ratio, 3.5) between a family history of type 2 diabetes mellitus and the development of HDP, especially preeclampsia. CONCLUSIONS: It may be useful to screen pregnant women for plasma nitrites and serum triglycerides to identify those at risk of developing HDP, especially in women with a family history of type 2 diabetes mellitus.

Oral glycine administration attenuates diabetic complications in streptozotocin-induced diabetic rats.

Diabetes mellitus is a disease characterized by impaired glucose metabolism that leads to retinopathy, brain micro-infarcts and other complications. We have previously shown that oral glycine administration to diabetic rats inhibits non-enzymatic glycation of hemoglobin and diminishes renal damage. In this work, we evaluated the capacity of the amino acid glycine (1% w/v, 130 mM) to attenuate diabetic complications in streptozotocin (STZ)-induced diabetic Wistar rats and compared them with non-treated or taurine-treated (0.5% w/v, 40 mM) diabetic rats. Glycine-treated diabetic rats showed an important diminution in the percentage of animals with opacity in lens and microaneurysms in the eyes. Interestingly, there was a diminished expression of O-acetyl sialic acid in brain vessels compared with untreated diabetic rats (P<0.05). Additionally, peripheral blood mononuclear cells isolated from glycine-treated diabetic rats showed a better proliferative response to PHA or ConA than those obtained from non-treated diabetic rats (P<0.05). Glycine-treated rats had a less intense corporal weight loss in comparison with non-treated animals. Our results suggest that administration of glycine attenuates the diabetic complications in the STZ-induced diabetic rat model, probably due to inhibition of the non-enzymatic glycation process.