Prematurity and congenital malformations differ according to the type of pregestational diabetes.

BACKGROUND: Diabetes mellitus (DM) is the most common metabolic disorder in pregnancy. Women with Type 2 DM seems to have no better perinatal outcomes than those with Type 1 DM. METHODS: Single-center prospective cohort observational study. Pregnant women with diabetes (141 with Type 1 DM and 124 with Type 2 DM) that were followed in the university hospital between 2009 and 2021 were included in this study. Clinical data and obstetric and perinatal outcomes were collected. RESULTS: As expected, women with Type 1 DM were younger and had a longer duration of diabetes than women with Type 2 DM. Obesity and chronic hypertension were higher in the group of women with Type 2 DM and their value of HbA1c in the second and third trimesters were lower than in Type 1 DM. No differences in prematurity were found, but more extreme prematurity was observed in Type 2 DM, as well as a higher rate of congenital malformations. The frequency of hypoglycemia and the weight of the newborn was higher in Type 1 DM. The maternal independent factors related to the weight of the newborn were: the glycemic control at the third trimester, the weight gain during pregnancy, and pregestational BMI. CONCLUSIONS: Newborns born to mothers with Type 1 DM were larger and had a higher frequency of hypoglycemia, while congenital malformations and precocious preterm was more associated to Type 2 DM. Metabolic control, weight gain and pregestational weight were important determinants of both obstetric and neonatal complications.

Active paraplegics are protected against exercise-induced oxidative damage through the induction of antioxidant enzymes.

STUDY DESIGN: Experimental study. OBJECTIVES: Exercise improves functional capacity in spinal cord injury (SCI). However, exhaustive exercise, especially when sporadic, is linked to the production of reactive oxygen species that may have a detrimental effect on SCI. We aimed to study the effect of a single bout of exhaustive exercise on systemic oxidative stress parameters and on the expression of antioxidant enzymes in individuals with paraplegia. SETTING: The study was conducted in the Physical Therapy department and the Physical Education and Sports department of the University of Valencia. METHODS: Sixteen paraplegic subjects were submitted to a graded exercise test (GET) until volitional exhaustion. They were divided into active or non-active groups. Blood samples were drawn immediately, 1 and 2 h after the GET. We determined plasma malondialdehyde (MDA) and protein carbonylation as markers of oxidative damage. Antioxidant gene expression (catalase and glutathione peroxidase-GPx) was determined in peripheral blood mononuclear cells. RESULTS: We found a significant increase in plasma MDA and protein carbonyls immediately after the GET (P<0.05). This increment correlated significantly with the lactate levels. Active paraplegics showed lower levels of exercise-induced oxidative damage (P<0.05) and higher exercise-induced catalase (P<0.01) and GPx (P<0.05) gene expression after the GET. CONCLUSIONS: These results suggest that exercise training may be useful in SCI patients to develop systemic antioxidant defenses that may protect them against exercise-induced oxidative damage.

Estrogen Replacement Therapy Induces Antioxidant and Longevity-Related Genes in Women after Medically Induced Menopause.

Females live longer than males in many species, including humans, and estrogens are in part responsible for this protection against aging. We reported previously that estrogens can protect rats against oxidative stress, by inducing antioxidant and longevity-related genes. Thus, this study was aimed at confirming the ability of estrogens to upregulate antioxidant and longevity-related genes in humans. For this purpose, we selected 16 women of reproductive age (18-42 years old) undergoing a fertility treatment that includes a medically induced menopause, at the Valencian Infertility Institute. We took blood samples at each time point of the treatment (basal, induced menopause, estrogen, and estrogen plus progesterone replacement therapy). mRNA expression of antioxidant and longevity-related genes in peripheral blood mononuclear cells (PBMC) was determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Determination of reduced glutathione (GSH) in total blood was carried out using high-performance liquid chromatography (HPLC). As expected, we found that medically induced menopause significantly decreased sexual hormone (estrogens and progesterone) levels. It also lowered glutathione peroxidase (GPx), 16S rRNA, P21, and TERF2 mRNA expression and blood GSH levels. Estrogen replacement therapy significantly restored estrogen levels and induced mRNA expression of manganese superoxide dismutase (MnSOD), GPx, 16S rRNA, P53, P21, and TERF2 and restored blood GSH levels. Progesterone replacement therapy induced a significant increase in MnSOD, P53, sestrin 2 (SENS2), and TERF2 mRNA expression when compared to basal conditions. These findings provide evidence for estrogen beneficial effects in upregulating antioxidant and longevity-related genes in women.

Targeting Alzheimer's disease with multimodal polypeptide-based nanoconjugates.

Alzheimer's disease (AD), the most prevalent form of dementia, remains incurable mainly due to our failings in the search for effective pharmacological strategies. Here, we describe the development of targeted multimodal polypeptide-based nanoconjugates as potential AD treatments. Treatment with polypeptide nanoconjugates bearing propargylamine moieties and bisdemethoxycurcumin or genistein afforded neuroprotection and displayed neurotrophic effects, as evidenced by an increase in dendritic density of pyramidal neurons in organotypic hippocampal culture. The additional conjugation of the Angiopep-2 targeting moiety enhanced nanoconjugate passage through the blood-brain barrier and modulated brain distribution with nanoconjugate accumulation in neurogenic areas, including the olfactory bulb. Nanoconjugate treatment effectively reduced neurotoxic ß amyloid aggregate levels and rescued impairments to olfactory memory and object recognition in APP/PS1 transgenic AD model mice. Overall, this study provides a description of a targeted multimodal polyglutamate-based nanoconjugate with neuroprotective and neurotrophic potential for AD treatment.

Centenarians: An excellent example of resilience for successful ageing.

Centenarians are remarkable not only because of their prolonged life, but also because they compress morbidity until the very last moments of their lives, thus being proposed as a model of successful, extraordinary ageing. From the medical viewpoint, centenarians do not escape the physiological decline or the age-related diseases or syndromes (i.e. frailty), but the rate of such processes is slow enough to be counterbalanced by their increased intrinsic capacity to respond to minor stresses of daily life (i.e. resilience). These new concepts are reviewed in this paper. Allostatic stresses lead to a chronic low-grade inflammation that has led to the proposal of the "inflammaging" theory of ageing and frailty. The biology of centenarians, described in this review, provides us with clues for intervention to promote healthy ageing in the general population. One of the major reasons for this healthy ageing has to do with the genetic signature that is specific for centenarians and certainly different from octogenarians who do not enjoy the extraordinary qualities of centenarians.

Effect of the administration of a probiotic with a combination of Lactobacillus and Bifidobacterium strains on antibiotic-associated diarrhea.

OBJECTIVE: The aim of this study is to analyze the effect, safety and tolerability of a specific probiotic combination of Lactobacillus and Bifidobacterium strains (Pearls IC©) on antibiotic associated diarrhea due to amoxicillin-clavulanic acid treatment. METHODS: Pilot, unicentric, randomized, double-blind, parallel group, placebo-controlled study (probiotic vs. placebo for 30 days). Target population: Adult patients, both sexes treated with amoxicillin-clavulanic acid (850mg / 125mg every 8h /orally) for 7 days who attended the Emergency Department (Dexeus Hospital, Barcelona) between January and April of 2018 with prior signed informed consent with a follow up at 30 days. Variables: The differences between day 0 and day 30 of the number of daily stools and duration of diarrhea were evaluated; Stool consistency according to Bristol Stool Form, Quality of intestinal life. Subjective evaluation and evaluation of adverse effects of the product through a specifically designed questionnaire. RESULTS: Thirty-six subjects were included (18 per group) 25 females and 11 males, average age of 38.5 years (range 19-65 years). Pearls IC© delayed between 4 and 5 days the appearance of the diarrheic episode vs. placebo (p <0.001). The results of the quality of life assessment showed an improvement at the end of the 30 days period but without difference vs placebo. The results of the subjective assessment were in favor of the probiotic with higher rate of like responses than placebo. CONCLUSIONS: Pearls IC© demonstrated its beneficial effect on antibiotic associated diarrhea by delaying the onset of diarrhea and showed a tendency to decrease the number of daily stools vs. placebo.

Resveratrol shifts energy metabolism to increase lipid oxidation in healthy old mice.

OBJECTIVES: The objective of this work was to determine the specific mechanisms by which resveratrol inhibits lipogenesis and stimulates lipolysis. METHODS: Twelve male mice were individually introduced into a metabolic cage for 24 h to measure basal metabolic rate, prior to intervention. They were randomly divided into two groups, resveratrol (RSV) and control (C), and administered resveratrol intraperitoneally or vehicle, respectively, for two consecutive days. After 24 h, the metabolic energy expenditure was again determined for 24 h, before mice were sacrificed. Protein and gene expression of different enzymes related to metabolism in the hepatic tissue, adipose tissue and gastrocnemius of mice were analyzed by RT-PCR, western blot or ELISA. RESULTS: We report that resveratrol lowers the respiratory quotient in old mice and that this may be due to the activation of fatty acid mobilization from white adipose tissue (because hormone-activated lipase expression is increased) and fatty acid transport into mitochondria and eventual oxidation in muscle and liver (because transport enzymes and beta oxidation enzymes are also increased). Indeed, we have observed that resveratrol in vivo causes an increase in the expression and phosphorylation of AMPKα in liver, muscle and adipose tissue and an increase in the expression of acyl-CoA synthetase, of carnitine palmitoyl transferase 1 and of carnitine acylcarnitine translocase, all enzymes involved in lipid catabolism. On the other hand, the levels of acetyl-CoA carboxylase as well as those its product, i.e. malonyl CoA, are decreased. CONCLUSIONS: We conclude that a controlled dose of resveratrol activates fatty acid mobilization and degradation and inhibits fatty acid synthesis in old mice. This is the first time that these effects of resveratrol in lipid metabolism in healthy old (non-obese) animals are reported.

Exceptional human longevity is associated with a specific plasma phenotype of ether lipids.

A lipid profile resistant to oxidative damage is an inherent trait associated with animal lifespan. However, there is a lack of lipidomic studies on human longevity. Here we use mass spectrometry based technologies to detect and quantify 137 ether lipids to define a phenotype of healthy humans with exceptional lifespan. Ether lipids were chosen because of their antioxidant properties and ability to modulate oxidative stress. Our results demonstrate that a specific ether lipid signature can be obtained to define the centenarian state. This profile comprises higher level of alkyl forms derived from phosphatidylcholine with shorter number of carbon atoms and double bonds; and decreased content in alkenyl forms from phosphatidylethanolamine with longer chain length and higher double bonds. This compositional pattern suggests that ether lipids from centenarians are more resistant to lipid peroxidation, and that ether lipid signature expresses an optimized feature associated with exceptional human longevity. These results are in keeping with the free radical theory of aging.

Sarcopenia, frailty and their prevention by exercise.

Sarcopenia is a major component of the frailty syndrome, both being considered as strong predictors of morbidity, disability, and death in older people. In this review, we explore the definitions of sarcopenia and frailty and summarize the current knowledge on their relationship with oxidative stress and the possible therapeutic interventions to prevent or treat them, including exercise-based interventions and multimodal strategies. We highlight the relevance of the impairment of the nervous system and of the anabolic response (protein synthesis) in muscle aging leading to frailty and sarcopenia. We also discuss the importance of malnutrition and physical inactivity in these geriatric syndromes. Finally, we propose multimodal interventions, including exercise programs and nutritional supplementation, as the strategies to prevent and treat both sarcopenia and frailty.

Centenarians maintain miRNA biogenesis pathway while it is impaired in octogenarians.

Centenarians but not octogenarians up regulate the expression of miRNAs, as we previously reported. We have looked into miRNA biogenesis. We show that RNA POL II, DROSHA, EXPORTIN 5 and DICER, are up-regulated in centenarians compared with octogenarians. Furthermore, factors involved in the control of these miRNAs biogenesis genes are also up-regulated in centenarians. Therefore, the up-regulation of miRNA expression in centenarians can be explained in part because miRNA biogenesis pathway is depressed in octogenarians (ordinary aging) while it is maintained in centenarians (extraordinary aging).

Properties of Resveratrol: In Vitro and In Vivo Studies about Metabolism, Bioavailability, and Biological Effects in Animal Models and Humans.

Plants containing resveratrol have been used effectively in traditional medicine for over 2000 years. It can be found in some plants, fruits, and derivatives, such as red wine. Therefore, it can be administered by either consuming these natural products or intaking nutraceutical pills. Resveratrol exhibits a wide range of beneficial properties, and this may be due to its molecular structure, which endow resveratrol with the ability to bind to many biomolecules. Among these properties its activity as an anticancer agent, a platelet antiaggregation agent, and an antioxidant, as well as its antiaging, antifrailty, anti-inflammatory, antiallergenic, and so forth activities, is worth highlighting. These beneficial biological properties have been extensively studied in humans and animal models, both in vitro and in vivo. The issue of bioavailability of resveratrol is of paramount importance and is determined by its rapid elimination and the fact that its absorption is highly effective, but the first hepatic step leaves little free resveratrol. Clarifying aspects like stability and pharmacokinetics of resveratrol metabolites would be fundamental to understand and apply the therapeutic properties of resveratrol.

[Comparative study of soluble interleukin 2 receptor and adenosine deaminase levels in tuberculous and other etiologies pleural fluids]. / Estudio comparativo de los niveles de receptor soluble de interleucina 2 y adenosín-desaminasa en líquidos pleurales tuberculosos y de otras etiologías.

In order to better understand the immunological mechanisms involved in host protection against Mycobacterium tuberculosis infection, we studied soluble interleukin 2 receptor (sIL-2R) concentration in tuberculous pleural exudates as well as in pleural fluids of non-mycobacterial etiology. We collected pleural fluid from 40 patients: 10 with tuberculous bacterial pneumonia and 10 with trasudate. Soluble IL-2R was measured in the stored specimens using a standard ELISA technique. In patients with tuberculosis, sIL-2R in pleural fluid was 14,666 +/- 5,634 U/ml, significantly higher than was detected in any other group, being 4,341 +/- 2,655 U/ml in pneumonic exudates, 5,542 +/- 3,682 U/ml in neoplastic exudates and 1,377 +/- 125 in trasudates (p < 0.001). Also, an excellent correlation was demonstrated between adenosine-desaminase (ADA) and sIL-2R in tuberculous pleural fluids, with p < 0.001 and r = 0.805. In pleuropulmonary tuberculosis, compartmentalization of the immune response in the pleural space is responsible for the significantly higher levels of sIL-2R that were found in tuberculous pleural liquids compared with the ones detected in other diseases. This observation, as well as the demonstration of a good correlation between sIL-2R and ADA, suggest the possible usefulness of this molecule as an additional marker in the differential diagnosis of pleural effusions, though in the present study it appears to be less reliable than ADA.

[Outbreak of influenza A(H1N1)/2009: description of cases and crisis management in a ICU in Reunion Island]. / Épidémie de grippe A(H1N1/)2009 : description des cas et expérience de gestion de crise dans un service de réanimation réunionnais.

OBJECTIVES: to describe the characteristics, treatment and outcome of critically ill patients with influenza A(H1N1) infection at St Pierre Hospital in Reunion Island during the 2009 outbreak, as well as the measures of care reorganization implemented to face them. PATIENTS AND METHODS: prospective observational study of probable and confirmed cases of influenza A (H1N1)/2009 infection concerning hospitalized patients in a polyvalent intensive care unit (ICU). RESULTS: thirteen patients have been included between August and September 2009. Three (23 %) didn't have any medical history. The median age was 42 [22-69]. Eleven have required pulmonary ventilation for 10.3 days (± 8). Three (23 %) have developed an ARDS. Three patients (23 %) died. To cope with the influx of cases and considering our situation of geographic isolation, it has been needed to totally rework the organization of care: set-up of a specific welcoming channel, division into sectors of the department, opening of additional beds, new on-duty assignment, inter and intra hospital cooperation. CONCLUSION: reunion Island has been an experimental lab of crisis management during the H1N1/2009 epidemic, several months ahead of the mother country. To anticipate the reorganization of care in intensive care units during an outbreak period, particularly in small units or units isolated like ours, looks to us a must so to quietly face a sharp influx of patients.

A simple method of correcting diffusing capacity for alveolar volume reduction in restrictive lung diseases.

We studied the discriminative power of the transfer factor (TLCO), KCO (TLCO/Va) and ZCO (a corrected TLCO according to alveolar volume measured (Va), introduced by our group), in order to differentiate diffuse interstitial disease from other restrictive diseases. Measurements were taken in 46 subjects, divided into two groups: Pure restriction (group 1: normal subjects with voluntary restriction and diseased subjects) and (2) diffuse interstitial restriction (group 2). There were no statistical differences in Va between groups 1 and 2. TLCO was statistically lower in groups 1 and 2 in comparison with the control group (normal values of our laboratory in test with Va greater than 90% of predicted) and showed a significant difference when group 1 was compared with group 2. Similar results (but with higher values than those of the control group) were found for KCO. A similar difference exists in ZCO only when group 2 is compared with group 1, but not when group 1 is compared with the control group. The corrected diffusion capacity ZCO yields the highest discriminative power.

Spontaneous pneumomediastinum after cocaine inhalation.

We report a case of spontaneous pneumomediastinum after cocaine inhalation. The possible mechanisms implicated in an inspiratory manoeuvre are discussed.

[Rational use of antibiotics in pediatrics: impact of a rapid test for detection of beta-haemolytic group A streptococci in acute pharyngotonsillitis]. / Empleo racional de los antibióticos en pediatría: impacto de la aplicación de un test rápido de detección de estreptococo beta-hemolítico del grupo A en la faringoamigdalitis aguda.

OBJECTIVES: To assess the reliability and validity of a rapid test for the identification of Streptococcus pyogenes in the pharyngeal exudate of children presenting with pharyngotonsillitis. To evaluate the impact of its use in outpatient clinics on antibiotic use, on the incidence of second medical visits and complications, and on the degree of parental satisfaction. PATIENTS AND METHODS: After a clinical diagnosis of acute pharyngitis was established and written informed consent obtained from the parents, dual throat swabs were collected from 430 children who attended the emergency department of our hospital or the pediatric offices of three health centers in our area. The first specimen was examined by the rapid test, QuickVue Flex Strep A, and the second one was sent to the laboratory for conventional culture. As a rule, antibiotics were indicated only when the rapid test was positive. Special emphasis was placed on explaining to parents that treatment was not necessary when the test was negative. Telephone follow-up was provided to the family during the next four weeks, after which a satisfaction survey was carried out. RESULTS: The sensitivity of the investigated rapid test was 91.2% (negative predictive value: 96.5%) and specificity was 96.2% (positive predictive value: 90.4%). Antibiotics were given to 41.9% of the patients, approximately half the expected rate in the absence of the rapid test. There was no significant difference in the number of second visits or hospitalizations between the groups of treated and non-treated subjects. Clinical evolution was good in all cases. The degree of parental satisfaction was very high, independent of the treatment given to the patients. CONCLUSIONS: The rapid test for the detection of group A streptococci is a reliable tool for the selection of patients able to benefit from antibiotic treatment. It is easy to handle and apply and its use allows a significant reduction in the administration of antibiotics in pharyngotonsillitis. Most users accept and are satisfied with this novel diagnostic and therapeutic procedure.

Serum soluble interleukin-2 receptor: a useful indicator of the clinical course in pulmonary tuberculosis.

SETTING: In tuberculosis both host protection and most pathogenic mechanisms depend on T lymphocytes. After activation by mycobacterial antigens, T cells both secrete interleukin-2 (IL-2) and express a high affinity receptor for this molecule (IL-2R) on their own surface. A soluble fraction of IL-2 receptor (sIL-2R), released from cell membrane, is detectable in serum and its concentration is known to be elevated in tuberculosis. OBJECTIVE: To ascertain the role of sIL-2R as an indicator of clinical evolution and response to antituberculosis treatment. DESIGN: A prospective study, in which we have measured serum sIL-2R in 52 patients (42 with active and 10 with inactive pulmonary tuberculosis) and in 36 healthy controls. In 20 patients, serum sIL-2R levels were measured serially throughout the treatment. Levels of sIL-2R were correlated to clinical and radiological parameters. RESULTS: Serum sIL-2R was significantly increased in patients with tuberculosis as compared to healthy subjects. Both the radiological findings and the clinical state of patients showed a good correlation with sIL-2R. All patients with normal values of sIL-2R 6 months after starting therapy had a favourable clinical evolution. CONCLUSION: Serum sIL-2R is a useful marker of the clinical state and evolution of patients with pulmonary tuberculosis. The detection of permanently high values beyond 3-6 months of treatment suggests that additional drugs or prolonged administration would be advisable in order to ensure full recovery.