Menstrual cycle and gonadal steroid effects on symptomatic hyperammonaemia of urea-cycle-based and idiopathic aetiologies

Summary We report two female patients, one with a known inborn error of ureagenesis and the other of unknown cause, in whom recurrent, transient episodes of severe hyperammonaemia increased in frequency and severity with sexual maturity and parturition. Both responded to ovarian steroids administered continuously to suppress ovulation and menstruation, and ultimately to simple hysterectomy. These studies suggest a new therapeutic approach to defective ureagenesis in female patients and a relationship between ammonia production or disposal and the menstrual cycle.     

In vitro polymorphonuclear neutrophil function in surgical patients does not correlate with anergy but with "activating" processes such as sepsis or trauma

We studied 199 preoperative patients admitted for esophagogastric, gastric, colonic, or rectal resections, 132 patients with severe blunt trauma, 180 surgical intensive care unit patients with major sepsis, and 95 laboratory controls in order to clarify the role of polymorphonuclear neutrophil (PMN) adherence and chemotaxis to outcome. Patients were also stratified by the delayed-type hypersensitivity response to five ubiquitous antigens. PMN adherence and PMN chemotaxis were not different in preoperative reactive or anergic patients and were equal to the control values, whereas both reactive patients and anergic patients showed altered PMN function after trauma or sepsis. There was no difference in PMN adherence or chemotaxis between patients who died and those who lived. Multiple logistic regression analysis showed that patient age, delayed-type hypersensitivity, and admission serum albumin level, not PMN adherence or chemotaxis, were significantly related to septic mortality. We concluded that altered circulating PMN adherence and chemotaxis is seen in all patients after an "activation" event such as trauma or sepsis. This is a nonspecific immune alteration not related to specific immune events such as delayed-type hypersensitivity; it does not correlate with patient outcome and should not be used as a predictive variable.     

Proximal tubular epithelial cell integrins respond to high glucose by altered cell-matrix interactions and differentially regulate matrixin expression

Thickening of the tubular basement membrane (TBM) occurs in diabetic nephropathy, but the effects of high glucose on the functional aspects of proximal tubular epithelial cells are not clearly understood. In the present study, we examined the effects of elevated glucose concentrations on (a) integrin expression by human proximal tubular epithelial cells (HK-2) and integrin-mediated interactions with type IV collagen (colIV) and laminin, major components of TBM; (b) the expression of matrixins/matrix metalloproteinases (MMPs), which is regulated by integrins; and (c) the expression of tissue inhibitors of metalloproteinases (TIMPs). HK-2 cells cultured in 25 mM glucose underwent a reduction of the expression of alpha3, beta1, alpha(v)beta3, and alpha5 integrin subunits, with a concomitant increase of the alpha2 subunit, compared with cells grown in 5 mM glucose. Adhesion experiments demonstrated that high glucose led to increased cell adhesion on either colIV or laminin. Experiments of competition of adhesion using anti-integrin antibodies indicated that HK-2 cells in 5 mM glucose used mainly alpha(v)beta3 and alpha5beta1 integrins to adhere to colIV, whereas in 25 mM glucose they additionally used alpha2beta1. In the case of laminin, a beta1-mediated adhesion was observed when HK-2 cells were in 5 mM glucose, whereas in 25 mM glucose, alpha2beta1 and alpha(v)beta3 were also involved. Elevated glucose concentrations resulted in decreased expression of MMP-9 and MMP-2, whereas an increase in TIMP-1 and a decrease in TIMP-2 expression were observed. We also examined which integrins mediated the expression and secretion of matrixins MMP-2 and MMP-9. Ligation of alpha3beta1 with mAbs resulted in induction of MMP-2 expression and secretion, whereas antibody ligation of alpha(v)beta3 led to down-regulation of MMP-9. The above data implicate integrins of proximal tubular epithelial cells in the regulation of MMPs and in the development of TBM thickening in diabetic nephropathy.     

Cell proliferation rate and nuclear morphometry in Roberts syndrome

Roberts syndrome (RS) is a rare autosomal recessive disorder characterized primarily by symmetric reduction anomalies of all limbs, growth retardation and craniofacial abnormalities. Most RS patients are reported to present a typical abnormality of their constitutive heterochromatin, accompanied by abnormal cytological growth characteristics. We present an extremely severe case of an RS fetus, karyotypically documented, with a clinical presentation including growth deficiency, tetraphocomelia, frontal meningocele, craniofacial abnormalities and penile enlargement with hypospadias. Nuclear morphometrical analysis in tissues of various organs revealed a reduced nuclear size in RS as compared to normal controls, and statistically significant differences in morphometric parameters related to the nuclear shape. Immunohistochemical study of the same organs showed a reduced expression of proliferating cell nuclear antigen in the presented case, thus indicating a decreased cell proliferation rate in RS. Our results reconfirm previously reported findings in cultured fibroblasts of RS cases, thereby reinforcing on a histologic level, the hypothesis that reduced cell proliferation may be involved in the growth retardation and the reduction abnormalities observed in RS.     

Fetal heart rate and umbilico-placental Doppler flow velocity waveforms in early pregnancies with a chromosomal abnormality and/or an increased nuchal translucency thickness

Fetal heart rate, umbilical artery pulsatility index, end-diastolicflow,nuchal translucency thickness and placental thickness were recordedin 250 women with a viable singleton pregnancy undergoing chorionicvillous sampling for fetal karyotyping at 11–14 weeksof gestation. The fetal karyotype was normal in 210 cases andabnormal in 40, including 21 with trisomy 21, 13 with trisomy18, three with triploidy, two with monosomy X and one with trisomy13. A total of 52 fetuses with a normal karyotype had a nuchaltranslucency 3 mm and were considered separately. There wasa stable and significant increase in the mean fetal heart ratein trisomy 21 pregnancies compared to controls. No significantdifference was found for the other variables between the groups.In chromosomally normal fetuses with an increased nuchal thickness,the development of fetal heart rate and compliance of the umbilico-placentalcirculation were within the normal ranges. Some fetuses withtrisomy 18 or triploidy had an increased resistance to bloodflow in the umbilical artery, which was probably due to abnormalplacental development.     

Neural networks involved in mathematical thinking: evidence from linear and non-linear analysis of electroencephalographic activity

Using linear and non-linear methods, electroencephalographic (EEG) signals were measured at various brain regions to provide information regarding patterns of local and coordinated activity during performance of three arithmetic tasks (number comparison, single-digit multiplication, and two-digit multiplication) and two control tasks that did not require arithmetic operations. It was hypothesized that these measures would reveal the engagement of local and increasingly complex cortical networks as a function of task specificity and complexity. Results indicated regionally increased neuronal signalling as a function of task complexity at frontal, temporal and parietal brain regions, although more robust task-related changes in EEG-indices of activation were derived over the left hemisphere. Both linear and non-linear indices of synchronization among EEG signals recorded from over different brain regions were consistent with the notion of more "local" processing for the number comparison task. Conversely, multiplication tasks were associated with a widespread pattern of distant signal synchronizations, which could potentially indicate increased demands for neural networks cooperation during performance of tasks that involve a greater number of cognitive operations.     

Effects of Three Different Family-Based Interventions in Overweight and Obese Children: The “4 Your Family” Randomized Controlled Trial

Childhood overweight and obesity prevalence has risen dramatically in the past decades, and family-based interventions may be an effective method to improve children’s eating behaviors. This study aimed to evaluate the effectiveness of three different family-based interventions: group-based, individual-based, or by website approach. Parents and school aged overweight or obese children, 8–12 years of age, were eligible for the study. A total of 115 children were randomly allocated in one of the three interventions, and 91 completed the study (79% compliance); Group 1 (n = 36) received group-based interventions by various experts; Group 2 (n = 30) had interpersonal family meetings with a dietitian; and Group 3 (n = 25) received training through a specifically developed website. Anthropometric, dietary, physical activity, and screen time outcomes were measured at baseline and at the end of the study. Within-group comparisons indicated significant improvement in body weight, body mass index (BMI)-z-score, physical activity, and screen time from baseline in all three study groups (p < 0.05). Furthermore, total body fat percentage (%TBF) was also decreased in Groups 2 and 3. Between-group differences varied with body weight and %TBF change, being larger in Group 3 compared to Groups 1 and 2, in contrast to BMI-z-score, screen time, and health behaviors, which were significantly larger in Group 2 than the other two groups. In conclusion, personalized family-based interventions are recommended to successfully improve children’s lifestyle and body weight status.     

Dietary Interventions with Polyphenols in Osteoarthritis: A Systematic Review Directed from the Preclinical Data to Randomized Clinical Studies

Osteoarthritis (OA) is the most common form of arthritis and a major cause of limited functionality and thus a decrease in the quality of life of the inflicted. Given the fact that the existing pharmacological treatments lack disease-modifying properties and their use entails significant side effects, nutraceuticals with bioactive compounds constitute an interesting field of research. Polyphenols are plant-derived molecules with established anti-inflammatory and antioxidant properties that have been extensively evaluated in clinical settings and preclinical models in OA. As more knowledge is gained in the research field, an interesting approach in the management of OA is the additive and/or synergistic effects that polyphenols may have in an optimized supplement. Therefore, the aim of this review was to summarize the recent literature regarding the use of combined polyphenols in the management of OA. For that purpose, a PubMed literature survey was conducted with a focus on some preclinical osteoarthritis models and randomized clinical trials on patients with osteoarthritis from 2018 to 2021 which have evaluated the effect of combinations of polyphenol-rich extracts and purified polyphenol constituents. Data indicate that combined polyphenols may be promising for the treatment of osteoarthritis in the future, but more clinical trials with novel approaches in the identification of the in-between relationship of such constituents are needed.