Hair testing applied to the assessment of in utero exposure to drugs: Critical analysis of 51 cases of the University Hospital of Verona

The work discusses the results of hair and urine testing performed in 51 cases of suspected in utero drug exposure handled at the University Hospital of Verona from 2016 to 2022. On the day of birth or the day after birth, urine from mother and newborn (UM and UN) and hair from mother (HM), newborn (HN) and father (HF), if possible, were collected. Urine underwent immunoassay and GC–MS analysis, whereas hair underwent LC–MS/MS and GC–MS/MS analysis. In 50 out of 51 cases, HM and/or HN were available. In 92% of them, hair testing resulted in a positive, often (>50% cases) for more than one class of substance. The most detected substances were cocaine, opiates, methadone and cannabinoids. Maternal segmental analysis showed a prevalent decreasing concentration trend during pregnancy in case of positivity for one class of substances, whereas, as expected, a neatly prevalent increasing trend in the case of positivity for more than one class of substances. In nine cases, HF was also available, resulting in all being positive, usually for the same classes of substances identified in HM, thus questioning parental responsibility. In 33 cases, urine samples from the mother or newborn were also collected. Of them, 27 cases (82%) tested positive, showing peri-partum drug consumption and then confirming the severity of the addiction. Hair testing showed to be a reliable diagnostic tool to investigate in utero drug exposure because of the possibility of obtaining a complete picture of maternal addictive behaviour and family background, thanks to segmental maternal hair analysis and father hair testing.     

Donor-recipient age interaction and the impact on clinical results after heart transplantation

To evaluate the impact of donor-recipient age matching on clinical outcomes after heart transplantation, a total of 509 patients (January 1990-December 2018, mean follow-up 111 ± 80 months) were stratified into 4 groups (young-R/young-D, young-R/old-D, old-R/young-D, old-R/old-D) according to the recipient (young-R < 60, old-R ≥ 60 years) and the donor (young-D < 50, old-D ≥ 50 years) age. No difference was found among 30-day mortality (P = .11) and postoperative complications between groups. Both unadjusted and adjusted survival was significantly higher for group young-R/young-D than that of other groups, in which survival was similar [adjusted HR for mortality of 2.0(1.2-3.4), 2.1(1.4-3.8) and 2.5(1.6-4.1) for groups old-R/young-D, young-R/old-D, old-R/old-D, respectively]. Compared to other groups, the incidence of grade ≥ 2 CAV was significantly lower in old-R/young-D group [adjusted HR 0.4(0.2-0.7)]. Among young recipients, the rate of acute grade ≥ 2 rejection episodes was higher in those receiving an old donor graft (P = .04). Old recipient groups were more affected by neoplasms and severe renal failure than young recipient groups (P < .01). Employment of hearts from donors ≥50 years of age adversely affects survival in recipients <60 years of age but does not influence outcomes in older recipients. Also, donor and recipient ages seem to have opposite effects on incidence of rejections and CAV of high grade.     

Micronized palmitoylethanolamide reduces joint pain and glial cell activation

Objective and design

Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation.

Materials and subject

TMJ was induced in rats with the injection of complete Freund’s adjuvant (CFA) emulsion into the left TMJ capsule.

Treatment

The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity.

Methods

Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection.

Results

CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1.

Conclusions

The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.

     

Saporin-S6: A Useful Tool in Cancer Therapy

Thirty years ago, the type 1 ribosome-inactivating protein (RIP) saporin-S6 (also known as saporin) was isolated from Saponaria officinalis L. seeds. Since then, the properties and mechanisms of action of saporin-S6 have been well characterized, and it has been widely employed in the construction of conjugates and immunotoxins for different purposes. These immunotoxins have shown many interesting results when used in cancer therapy, particularly in hematological tumors. The high enzymatic activity, stability and resistance to conjugation procedures and blood proteases make saporin-S6 a very useful tool in cancer therapy. High efficacy has been reported in clinical trials with saporin-S6-containing immunotoxins, at dosages that induced only mild and transient side effects, which were mainly fever, myalgias, hepatotoxicity, thrombocytopenia and vascular leak syndrome. Moreover, saporin-S6 triggers multiple cell death pathways, rendering impossible the selection of RIP-resistant mutants. In this review, some aspects of saporin-S6, such as the chemico-physical characteristics, the structural properties, its endocytosis, its intracellular routing and the pathogenetic mechanisms of the cell damage, are reported. In addition, the recent progress and developments of saporin-S6-containing immunotoxins in cancer immunotherapy are summarized, including in vitro and in vivo pre-clinical studies and clinical trials.     

Effects of experimental occlusal interference on body posture: an optoelectronic stereophotogrammetric analysis

In recent years, there has been increasing interest in the relationship between dental occlusion and body posture both among people and in scientific literature. The aim of the present longitudinal study is to investigate the effects of an experimental occlusal interference on body posture by means of a force platform and an optoelectronic stereophotogrammetric analysis. An occlusal interference of a 0‐ to 2‐mm‐thick glass composite was prepared to disturb the intercuspal position while not creating interference during lateral or protrusive mandibular excursions. Frontal and sagittal kinematic parameters, dynamic gait measurements and superficial electromyographic (SEMG) activity of head and neck muscles were performed on 12 healthy subjects. Measurements were taken 10 days before the application of the occlusal interference, and then immediately before the application, the day after it, and at a distance of 7 and 14 days under four different exteroceptive conditions. The outcomes of this study show that an occlusal interference does not modify significantly over time static and dynamic parameters of body posture under different exteroceptive conditions. It has a minimal influence only on the frontal kinematic parameters related to mandibular position, and it induces a transient increase of the activity of masticatory muscles. In this study, the experimental occlusal interference did not significantly influence the body posture during a 14‐day follow‐up period.     

Analyse de la variabilité respiratoire de la pression artérielle pulsée en ventilation spontanée

Volume expansion (VE) is one of the main symptomatic treatment of critically ill patients with hemodynamic shock. Although the aim of VE is to increase stroke volume (SV) and organ perfusion, inappropriate administration may lead to poor outcome. During invasive mechanical ventilation, dynamic parameters based on cardiopulmonary interactions have been developed in order to predict the hemodynamic response to VE. Variations in SV and estimates like pulse pressure variation (PPV) can be used in clinical practice in highly selected patients, with regular cardiac rhythm, undergoing mechanical ventilation without spontaneous respiratory cycles. Several studies have tested the diagnostic accuracy of PPV to predict fluid responsiveness in nonintubated, spontaneously breathing patients. Analysis methods for PPV are currently either too complex or inaccurate to be recommended in clinical practice. The aim of this review is to present the rationale for, and the limitations of the use of PPV to predict fluid responsiveness in critically ill spontaneously breathing patients without mechanical ventilation.     

Interdigestive Gastroduodenal Motility in Duodenal Ulcer: Role of Gastric Acid Hypersecretion

The interdigestive gastroduodenal motility was studied by means of a multilumen manometric probe in eight patients with active duodenal ulcer (group DU1) and in seven patients with hypersecretory gastroduodenitis (group GD). Both groups were selected on the basis of the presence of gastric acid hypersecretion. A group of five patients with non-active duodenal ulcer (group DU2) and a group of eight healthy subjects (group C) also were examined. Both of the latter groups were selected on the basis of the presence of normal gastric secretion. After a basal recording period of 200-300 min, in hypersecretory groups DU1 and GD, ranitidine was administered to decrease acid secretion; in normosecretory groups C and D2, impromidine was infused at two scalar doses to increase acid secretion. The basal recording showed in groups DU1 and GD a longer than normal time interval between consecutive activity fronts (AF) of the migrating motor complex (MMC cycle) and a shorter than normal percent of time occupied by AFs. In normal subjects and in DU2, the administration of the lowest dose of impromidine induced a motor pattern similar to that of the basal period of groups DU and GD, whereas the highest dose disrupted the MMC pattern that was replaced by an irregular motor activity. The results of this study indicate that duodenal ulcer with acid hypersecretion shows a marked inhibition of the MMC cycle that is not due to the ulcer itself, but to the increased acid secretion. In fact, the same motor pattern is observed in other hypersecretory states, both spontaneous and drug-induced, whereas DU with normal secretion showed a near normal motility. In active duodenal ulcer, the decreased incidence and duration of activity fronts may play a role in the pathogenesis of peptide ulcer, as it may impair the cyclic duodenal acid clearing, allowing a longer than normal contact of HCl with the duodenal mucosa.     

Circulating intercellular adhesion molecule 1 predicts non-specific elevation of α1-fetoprotein

Molecules governing cellular interactions have been suggested to be involved in the spurious elevation of 1-fetoprotein (AFP) in non-neoplastic liver disease. To explore this controversial issue, we measured AFP, circulating intercellular adhesion molecule 1 (cICAM-1), and common liver function tests in 111 patients (71 male, 40 female). Eighty-four patients had non-neoplastic chronic liver disease and 27 had hepatocellular carcinoma. The concentration of cICAM-1 was determined immunoenzymatically. In patients with non-neoplastic chronic liver disease, univariate analysis demonstrated a significant correlation between AFP and cholinesterase (R=–0.397,P<0.001), aspartate aminotransferase (R=0.421,P<0.001), bilirubin (R=0.231,P<0.05) and cICAM-1 (R=0.430,P<0.001). Multivariate analysis among these variables and AFP indicated cICAM-1 to be the strongest independent predictor of AFP. We conclude that cICAM-1 compares favourably with liver function tests in predicting non-specific AFP variations in non-neoplastic chronic liver disease, suggesting a link between targeting of the inflammatory damage to the hepatocyte and development of neoplasia.Abbreviations AFP 1-fetoprotein - cICAM-1 circulating intercellular adhesion molecule 1     

Plasma ghrelin,obesity, and the polycystic ovary syndrome: correlation with insulin resistance and androgen levels

In addition to its orexigenic properties, ghrelin has been shown to modulate the secretory pattern of pituitary hormones, and it may exert direct effects on peripheral organs such as the gonads and endocrine pancreas. To study possible interactions among ghrelin, glucose homeostasis, and the reproductive system, we investigated 10 obese women with polycystic ovary syndrome (OB-PCOS) in comparison with 10 age- and body mass index-matched obese subjects (OB). Plasma levels of insulin, glucose, androgens, and ghrelin were measured at baseline condition and after 7 months of therapy (hypocaloric diet + metformin or placebo). Plasma ghrelin levels were lower in OB-PCOS than in OB (P < 0.05). A strong negative correlation between ghrelin and androstenedione levels was found in both populations at baseline (OB-PCOS: P < 0.01; OB: P < 0.001) and after therapy (OB-PCOS: P < 0.01; OB: P < 0.05), whereas no correlation was found between ghrelin and other androgens. In both groups, the markers of insulin resistance in fasting and stimulated conditions (glucose/insulin ratio, homeostasis model insulin resistance index, homeostasis model applied to the oral glucose tolerance test) demonstrated decreased insulin sensitivity. However, a negative correlation between plasma ghrelin and all these markers was observed only in the OB-PCOS group (P < 0.05). Accordingly, a negative correlation between ghrelin variation and treatment-induced changes of the glucose/insulin ratio, HOMA-R, and HOMA(OGTT) was observed only in the OB-PCOS group (P < 0.05). In conclusion, OB-PCOS women have lower ghrelin levels than those expected based on the presence of obesity. Only in OB-PCOS, ghrelin negatively correlates with insulin sensitivity. In addition, regardless of the presence of PCOS, a marked negative correlation exists between ghrelin and androstenedione levels, suggestive of an interaction between ghrelin and steroid synthesis or action.