Pituitary adenomas: relationship between invasiveness and proliferative cell nuclear index

We evaluated clinically, radiologically and surgically a series of 76 pituitary adenomas. All cases were assessed immunohistochemically and in 49 patients the PCNA monoclonal antibody was measured. The most frequent types found were the bihormonal adenomas, followed by prolactinomas and non secreting adenomas. The bihormonal adenomas, non secreting adenonas and the sub unit alfa producing adenomas were proportionally more invase as determined by radiological criteria (CTscan or MRI). In 59 patients a transphenoidal approach was used, six cases were operated on transcranially and in 11 patients we used a combination of both approach. Total resection were achieved in 32 cases, most of which were microadenomas, in 15 cases the resection was subtotal and partial in 29 cases. Diabetes insipidus was the most frequent endocrine complication. It was observed that secreting adenomas tend to be associated with an increased PCNA and invasive adenomas correlated with PCNA 3 and 4. An improvement in vision was observed in 85% of macroadenomas seen after a total, subtotal or partial resection.     

Total sleep deprivation combined with lithium and light therapy in the treatment of bipolar depression: replication of main effects and interaction

The clinical usefulness of total sleep deprivation (TSD) in the treatment of bipolar depression is hampered by a high-rate short-term relapse. Previous literature has suggested that both long-term lithium treatment and light therapy could successfully prevent relapse. We randomized 115 bipolar depressed inpatients to receive three cycles of TSD, alone or in combination with morning light exposure, given at an intensity of 150 or 2500 lux. Forty-nine patients were undergoing long-term treatment with lithium salts (at least 6 months), while 66 patients were taking no psychotropic medication. Mood was self-rated by the Visual Analogue Scale three times a day during treatment. The results showed that both light therapy and ongoing lithium treatment significantly enhanced the effects of TSD on the perceived mood, with no additional benefit when the two treatments were combined. Subjective sleepiness during TSD, as rated by the self-administered Stanford Sleepiness Scale, was significantly reduced by light exposure, and was correlated with the outcome. This study confirms the possibility of obtaining a sustained antidepressant response to TSD in bipolar patients.     

The Antifungal Itraconazole Is a Potent Inhibitor of Chikungunya Virus Replication

Chikungunya virus (CHIKV) is the causative agent of chikungunya fever, a disabling disease that can cause long-term severe arthritis. Since the last large CHIKV outbreak in 2015, the reemergence of the virus represents a serious public health concern. The morbidity associated with viral infection emphasizes the need for the development of specific anti-CHIKV drugs. Herein, we describe the development and characterization of a CHIKV reporter replicon cell line and its use in replicon-based screenings. We tested 960 compounds from MMV/DNDi Open Box libraries and identified four candidates with interesting antiviral activities, which were confirmed in viral infection assays employing CHIKV-nanoluc and BHK-21 cells. The most noteworthy compound identified was itraconazole (ITZ), an orally available, safe, and cheap antifungal, that showed high selectivity indexes of >312 and >294 in both replicon-based and viral infection assays, respectively. The antiviral activity of this molecule has been described against positive-sense single stranded RNA viruses (+ssRNA) and was related to cholesterol metabolism that could affect the formation of the replication organelles. Although its precise mechanism of action against CHIKV still needs to be elucidated, our results demonstrate that ITZ is a potent inhibitor of the viral replication that could be repurposed as a broad-spectrum antiviral.     

Sex-Dependent Mediation of Leptin in the Association of Perilipin Polymorphisms with BMI and Plasma Lipid Levels in Children

Variations in the perilipin (PLIN) gene have been suggested to be associated with obesity and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the PLIN locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in PLIN1, and rs35568725 in PLIN2, were analyzed by RT-PCR in 1264 children aged 6–8 years. Our results showed a contrasting association of PLIN1 rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP PLIN2 rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration. In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in PLIN1 and PLIN2 with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the sex-dependent association of the PLIN SNPs with these variables.     

Nutritional Status after Roux-En-Y (Rygb) and One Anastomosis Gastric Bypass (Oagb) at 6-Month Follow-Up: A Comparative Study

Introduction: Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) are two effective bariatric surgical procedures with positive outcomes in terms of weight loss, comorbidities remission, and adverse events profiles. OAGB seems to carry a higher risk of malnutrition, but existing data are controversial. The aim of this study is to objectively evaluate and compare malnutrition in patients undergoing RYGB and OAGB. Methods: Retrospective monocentric study of obese patients undergoing RYGB or OAGB between the 15 September 2020 and the 31 May 2021. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score and compared between groups. The primary outcome was the mean CONUT score at 6 months. The secondary outcomes included the incidence of malnutrition, comorbidities, including hypertension, insulin resistance and type II diabetes mellitus, and weight loss. Results: 78 patients were included: 30 underwent RYGB and 48 underwent OAGB. At 6-Month Follow-Up there was no difference between groups in the mean CONUT score nor in incidence of malnutrition. In both groups, the nutritional status significantly worsened 6 months after surgery (preoperative and postoperative score of 0.48 ± 0.9 and 1.38 ± 1.5; p = 0.0066 for RYGB and of 0.86 ± 1.5 and 1.45 ± 1.3; p = 0.0422 for OAGB). Type II Diabetes mellitus (DMII) and hypertension remission were significant in the OAGB group with a 100% relative remission in the DMII-OAGB group (p = 0.0265), and a 67% relative remission in the hypertension-OAGB group (p = 0.0031). Conclusions: No difference in nutritional status has been detected between patients undergoing RYGB or OAGB at the 6-Month Follow-Up. Both procedures may have significant mal-absorptive effects leading to decline in nutritional status. OAGB may be more efficacious in inducing DMII and hypertension remission. Larger prospective studies dedicated specifically to nutritional status after gastric bypass are needed to confirm the impact of different bypass procedures on nutritional status.     

Influence of maternal labor time on delta-aminolevulinate dehydratase enzyme activity and markers of oxidative stress in newborns

Abstract

The purpose is to determine markers of oxidative stress related to the longer and shorter duration of labor (DOL) of pregnant women in the umbilical cord blood of neonates, not yet studied. Blood samples from the umbilical cord were collected from pregnant women with normal delivery and classified according to DOL in two groups: a group with DOL less than 310?min (n?=?33) and a group with DOL greater than or equal to 310?min (n?=?35). The oxidative stress parameters were analyzed by the quantification of thiobarbituric acid reactive substances (TBARS), nitrate/nitrite (NOx), protein thiol groups (P-SH) and non-protein (NP-SH), vitamin C and plasma iron reduction capacity (FRAP), in addition to the activity of the enzyme delta-aminolevulinate dehydratase (δ-ALA-D). The activity of the δ-ALA-D enzyme was shown to be decreased in longer DOL, however, the oxidant parameters and antioxidants were higher in the longer DOL, with the exception of NP-SH that was lower. The longer maternal DOL time is related to the alteration of δ-ALA-D enzyme activity and other parameters in neonates, suggesting an increase in the passage of maternal oxidative markers by umbilical cord blood.     

Amphiphilic Antimony(V) Complexes for Oral Treatment of Visceral Leishmaniasis

The need for daily parenteral administration is an important limitation in the clinical use of pentavalent antimonial drugs against leishmaniasis. In this study, amphiphilic antimony(V) complexes were prepared from alkylmethylglucamides (L8 and L10, with carbon chain lengths of 8 and 10, respectively), and their potential for the oral treatment of visceral leishmaniasis (VL) was evaluated. Complexes of Sb and ligand at 1:3 (SbL8 and SbL10) were obtained from the reaction of antimony(V) with L8 and L10, as evidenced by elemental and electrospray ionization-tandem mass spectrometry (ESI-MS) analyses. Fluorescence probing of hydrophobic environment and negative-staining transmission electron microscopy showed that SbL8 forms kinetically stabilized nanoassemblies in water. Pharmacokinetic studies with mice in which the compound was administered by the oral route at 200 mg of Sb/kg of body weight indicated that the SbL8 complex promoted greater and more sustained Sb levels in serum and liver than the levels obtained for the conventional antimonial drug meglumine antimoniate (Glucantime [Glu]). The efficacy of SbL8 and SbL10 administered by the oral route was evaluated in BALB/c mice infected with Leishmania infantum after a daily dose of 200 mg of Sb/kg for 20 days. Both complexes promoted significant reduction in the liver and spleen parasite burdens in relation to those in the saline-treated control group. The extent of parasite suppression (>99.96%) was similar to that achieved after Glu given intraperitoneally at 80 mg of Sb/kg/day. As expected, there was no significant reduction in the parasitic load in the group treated orally with Glu at 200 mg of Sb/(kg day). In conclusion, amphiphilic antimony(V) complexes emerge as an innovative and promising strategy for the oral treatment of VL.