Impact of variation in ADRB2, ADRB3, and GNB3 genes on body mass index and waist circumference in a Brazilian population.

The potential effect of variants in three catecholaminergic pathway genes (ADRB2, ADRB3, and GNB3) on obesity-related traits was investigated in an European-derived Brazilian population. Three-hundred and thirty-five individuals were screened for the ADRB2 Arg16Gly and Gln27Glu, ADRB3 Trp64Arg, and GNB3 814G-->A and 825C-->T polymorphisms using PCR-based methods. The association of the polymorphisms with quantitative variables was tested separately in each sex by analysis of covariance using general linear models, including age as a covariate. Only the ADRB2 Arg16Gly polymorphism was associated with higher body mass index and waist circumference. This association was restricted to the male sample. As the number of studies increases, it becomes clear that the genetic bases of obesity are complex, with sex-specific effects a playing an important role in its etiology. In the context of this European-derived population, the ADRB2 gene accounts for a significant part of obesity-related phenotypes in males.     

Potentiation of acute opioid-induced respiratory depression and reversal of tolerance by the calcium antagonist nimodipine in awake rats

Summary The interaction between sufentanil, a -opioid agonist, and the Ca²⁺ antagonist nimodipine on respiration and on the development of opioid tolerance in awake rats has been analyzed. Our previous work demonstrated that chronic treatment with nimodipine together with sufentanil increases the analgesic potency of the opioid 50 fold. Therefore, we have investigated whether the opioid-induced respiratory depression is potentiated in parallel with the analgesia. Ventilation was measured by the whole body plethysmographic method. In naive rats, sufentanil (10–80 g/kg) consistently induced a dose-dependent respiratory depression. Pretreatment with nimodipine (200 g/kg) potentiated this effect but to a lesser extent than it potentiated analgesia. After chronic administration of the opioid (2 g/h, 7 days) tolerance was manifested as a reduction in both the area under the time course curve and in the maximum effect. Nimodipine (1 g/h) administered concurrently with sufentanil for 7 days counteracted the tolerance to respiratory depression but no additional potentiation was observed. These results demonstrate that the interaction between nimodipine and sufentanil is not limited to antinociception but also exends to respiratory depression. However, compared with analgesia, the clinical relevance of a potential increase in opioid-induced respiratory depression by nimodipine may be negligible.Correspondence to: M. A. Hurlé at the above address     

Calcium channel modulation by dihydropyridines modifies sufentanil-induced antinociception in acute and tolerant conditions

Summary The study was aimed at elucidating the possible participation of l-type Ca²⁺ channel in the acute analgesic effect of an opiate and the development of tolerance to this action. Sufentanil, a selective p agonist, and two dihydropyridines, the Ca²⁺ antagonist nimodipine and the Ca²⁺ agonist Bay K 8644, were selected. The tail-flick test was used to assess the nociceptive threshold. In naive rats, nimodipine (200 g/kg) potentiated the analgesic effect of sufentanil reducing the ED₅₀ from 0.26 to 0.08 g/kg. Similar results were observed with its (–)-enantiomer Bay N 5248, while the (+) enantiomer Bay N 5247 was ineffective. Tolerance to the opiate was induced by chronic subcutaneous administration of sufentanil with minipumps (2 g/h, 7 days). In these conditions the dose-response curve to sufentanil was displaced to the right and the ED₅₀ was increased to 1.49 g/kg. In tolerant rats, nimodipine preserved its potentiating ability and prevented the displacement to the right of the sufentanil dose response-curve (ED₅₀ = 0.48 g/kg). When nimodipine was pumped (1 g/h, 7 days) concurrently with sufentanil, the development of tolerance to the opioid was not disturbed. However, the expression of tolerance was abolished and even the effect of acutely administered sufentanil was markedly potentiated (ED₅₀ = 0.03 g/kg). Similar experiments were performed with Bay K 8644. In naive rats, Bay K 8644 at a low dose (20 g/kg) that behaves as a calcium agonist, antagonized the analgesic effect of sufentanil (ED₅₀ = 0.58 g/kg), whereas at a high dose (200 g/kg) it potentiated this action (ED₅₀ = 0.15 g/kg). In tolerant rats, Bay K 8644 (20 g/kg) preserved its antagonizing ability inducing a displacement to the right of the sufentanildose-response curve (ED₅₀ = 4.2 g/kg). When Bay K 8644 was pumped (1 g/h, 7 days) concurrently with sufentanil, it enhanced the expression of tolerance to the opiate (ED₅₀ = 3.8 g/kg). These results suggest that the calcium fluxes through the l-type channel in neurones are functionally linked to the activation of the opiate receptor: the blockade of the channel increased the potency of sufentanil, whereas its activation reduced the potency of the opiate. In chronic experiments, DHPs concurrently administered with sufentanil did not affect the development of tolerance to the opiate. However, nimodipine prevented the expression of this phenomenon. Even more, the animals became hypersensitive to the opiate suggesting that the adaptative mechanisms induced by chronic opiate could be affected by chronic nimodipine.This work was supported by grants from Universidad de Cantabria-Caja Cantabria (1988) and Bayer AG, Wuppertal, FRGPredoctoral Fellow: Fondo de Investigaciones Sanitarias de la Seguridad Social.Send offprint requests to: M. A. Hurlé at the above address     

The ratio between carcinoma antigen-125 levels in the seminal plasma and serum may be a marker for fertilization in intracytoplasmic sperm injection

Objective: To assess the relationship between tumor marker carcinoma antigen-125 levels in seminal plasma and serum and fertilization rates in an IVF program, using intracytoplasmic sperm injection (ICSI).

Design: A prospective study.

Setting: IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Patient(s): Twenty-five infertile patients with severe oligo-terato-asthenospermia syndrome and 25 fertile male donors.

Intervention(s): None.

Main Outcome Measure(s): Serum and seminal plasma carcinoma antigen-125 concentrations and fertilization rate per cycle.

Result(s): In the infertile group, the seminal plasma carcinoma antigen-125 levels ranged from 22.0 to 1,284.0 U/mL (mean level ± SD, 229.9 ± 274.2 U/mL). In the normospermic fertile male donors, the seminal plasma carcinoma antigen-125 concentrations ranged from 12.2 to 336.7 U/mL (mean level ± SD, 110.1 ± 91.6 U/mL). This difference was statistically significant. The mean ± SD ratio between the seminal plasma/serum carcinoma antigen−125 levels differed significantly between the infertile group (47.9 ± 61.3) and the fertile male donors (5.7 ± 3.5). In the infertile group, the ratio between the seminal plasma/serum carcinoma antigen-125 levels was found to be negatively correlated with the oocyte fertilization rate.

Conclusion(s): The ratio between carcinoma antigen−125 levels in the seminal plasma and serum may be an indirect marker for male infertility and fertilization rate in IVF treatment using ICSI.     

Serum PDGF-AB in pleural mesothelioma.

Overexpression of platelet-derived growth factor (PDGF) has been observed in lung and pleural tumors. The aim of this study was to evaluate the diagnostic and prognostic role of serum PDGF in pleural mesothelioma (PM). Four groups of subjects were studied: 93 malignant PM patients, 33 primary non small cell lung cancer patients, 51 subjects exposed to asbestos, defined as high-risk controls, and 24 healthy controls. PDGF-AB mean concentration was higher in PM patients (45.8 ng/ml) than in high-risk controls (33.1 ng/ml) and healthy controls (26.8 ng/ml). Using the cut-off level of 49.8 ng/ml, corresponding to the mean+2SD of PDGF-AB in healthy controls, 43% of PM patients showed positive PDGF-AB levels. Survival was evaluated in 82 PM patients. At the end of the follow-up (median 9.8 months) 80.5% of patients had died. Median survival was 13.1 and 7.9 months for patients with PDGF-AB lower and higher than the cut-off, respectively. Adjusting for age, sex, histology and platelet count, positive PDGF-AB levels were associated with lower survival (OR=1.2, 95%CI: 0.9-1.6), even if not significantly so. In conclusion, serum PDGF may represent a useful additional parameter to prognostic factors already available for PM.     

Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage

The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4 ± 1.9 mg GAE/g), condensed tannins (58.4 ± 2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe²⁺-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE + Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption.     

Correction to: Gene Editing Rescues in Vitro T Cell Development of RAG2-Deficient Induced Pluripotent Stem Cells in an Artificial Thymic Organoid System

Journal of Clinical Immunology - A Correction to this paper has been published: https://doi.org/10.1007/s10875-021-01030-6     

Are computational applications the “crystal ball” in the IVF laboratory? The evolution from mathematics to artificial intelligence

Mathematics rules the world of science. Innovative technologies based on mathematics have paved the way for implementation of novel strategies in assisted reproduction. Ascertaining efficient embryo selection in order to secure optimal pregnancy rates remains the focus of the in vitro fertilization scientific community and the strongest driver behind innovative approaches. This scoping review aims to describe and analyze complex models based on mathematics for embryo selection, devices, and software most widely employed in the IVF laboratory and algorithms in the service of the cutting-edge technology of artificial intelligence. Despite their promising nature, the practicing embryologist is the one ultimately responsible for the success of the IVF laboratory and thus the one to approve embracing pioneering technologies in routine practice. Applied mathematics and computational biology have already provided significant insight into the selection of the most competent preimplantation embryo. This review describes the leap of evolution from basic mathematics to bioinformatics and investigates the possibility that computational applications may be the means to foretell a promising future for the IVF clinical practice.