Hyaluronan-grafted particle clusters loaded with Mitomycin C as selective nanovectors for primary head and neck cancers

CD44, a well-documented cell surface receptor, is involved in cell proliferation, migration, signaling, adhesion, differentiation and angiogenesis, which are important properties for normal and cancerous cell function. We recently developed particle clusters coated with hyaluronan (termed gagomers; GAG), and showed that they can deliver the insoluble drug paclitaxel directly into CD44-over-expressing tumors in a mouse tumor model. Here, we tested primary head and neck cancers (HNC) and normal cells taken from the same patient, and found that although CD44 expression in both types of cells was high, GAGs bind only to the cancerous cells in a selective manner. We next formulated the anti cancer agent mitomycin C (MMC) in the GAGs. MMC-based chemoradiation is a potential treatment for HNC, however, due to patient's toxicity, MMC is not part of the standard treatment of HNC. MMC encapsulation efficiency was about 70% with a half-life drug efflux of 1.2 ± 0.3 days. The Ex vivo study of the targeted MMC-GAG showed significant increase in the therapeutic effect on HNC cells (compared to free MMC), while it had no effect on normal cells taken from the same patient. These results demonstrate the specificity of the nanovectors towards head and neck cancers, which might be applicable as future therapy to many CD44-expressing tumors.     

Can computerized cognitive tests assist in the clinical diagnosis of attention-deficit hyperactivity disorder?

A group of 34 children and adolescents suspected of having attention-deficit hyperactivity disorder were referred for a computerized evaluation that included sustained attention, working memory, planning, and set-shifting. Although only sustained attention had reasonable specificity, all tests had questionable contribution to the diagnostic evaluation.     

Effect of a Mediterranean meal on postprandial carotenoids, paraoxonase activity and C-reactive protein levels

BACKGROUND AND AIM: Atherosclerosis involves oxidative and inflammatory mediators regulated by fat and antioxidants. Therefore, we studied the postprandial evolution of plasma lipids, carotenoids, C-reactive protein (CRP), and human serum paraoxanase activity (PON1) following two different fatty meals. SUBJECTS AND METHODS: Eight healthy males consumed a 45% fat 1,000 Kcal Mediterranean-like (Med) meal (monounsaturated 61% of fat) compared to a Western-like (Wes) (saturated 57% of fat) meal. Blood was collected at baseline (time 0) 2, 4 and 7 h postprandial. Plasma lipids, glucose, insulin, total carotenoids, CRP, and PON1 were analyzed. RESULTS: There was a marginal increase in cholesterol and glucose after both meals. Triglycerides increased modestly (to less than 200 mg/dl) and insulin increased (more in the Wes-like meal) but still within normal range, indicating a low glycemic index for both meals. Only the Med-like meal resulted in a significant increase in both PON1 activity (16%, p < 0.02) and carotenoids (74%, p < 0.02) with a 2-hour postprandial decrease in CRP (6%, p < 0.02). CONCLUSION: A postprandial monounsaturated fatty acid rich meal increases both plasma carotenoids and PON1 with a decrease in CRP levels, thus providing a novel potential explanation to the protective properties of a Mediterranean diet against atherogenesis.     

Pomegranate juice sugar fraction reduces macrophage oxidative state, whereas white grape juice sugar fraction increases it

The antiatherogenic properties of pomegranate juice (PJ) were attributed to its antioxidant potency and to its capacity to decrease macrophage oxidative stress, the hallmark of early atherogeneis. PJ polyphenols and sugar-containing polyphenolic anthocyanins were shown to confer PJ its antioxidant capacity. In the present study, we questioned whether PJ simple or complex sugars contribute to the antioxidative properties of PJ in comparison to white grape juice (WGJ) sugars. Whole PJ decreased cellular peroxide levels in J774A.1 macrophage cell-line by 23% more than PJ polyphenol fraction alone. Thus, we next determined the contribution of the PJ sugar fraction to the decrease in macrophage oxidative state. Increasing concentrations of the PJ sugar fraction resulted in a dose-dependent decrement in macrophage peroxide levels, up to 72%, compared to control cells. On the contrary, incubation of the cells with WGJ sugar fraction at the same concentrations resulted in a dose-dependent increment in peroxide levels by up to 37%. The two sugar fractions from PJ and from WGJ showed opposite effects (antioxidant for PJ and pro-oxidant for WGJ) also in mouse peritoneal macrophages (MPM) from control as well as from streptozotocin-induced diabetic Balb/C mice. PJ sugar consumption by diabetic mice for 10 days resulted in a small but significant decrement in their peritoneal macrophage total peroxide levels and an increment in cellular glutathione content, compared to MPM harvested from control diabetic mice administrated with water. In contrast, WGJ sugar consumption by diabetic mice resulted in a 22% increment in macrophage total peroxide levels and a 45% decrement in cellular glutathione content. Paraoxonase 2 activity in macrophages increases under oxidative stress conditions. Indeed, macrophage paraoxonase 2 activity was decreased after PJ sugars supplementation, but increased after WGJ sugars supplementation. We conclude that PJ sugar fraction, unlike WGJ sugar fraction, decreases macrophage oxidative state under normal and under diabetic conditions. These antioxidant/antiatherogenic effects could be due to the presence of unique complex sugars and/or phenolic sugars in PJ.     

Morphological and Quantitative Study of the Myenteric Plexus in the Human Tenia Coli

The longitudinal muscle in the large intestine in humans and some other mammalian species is concentrated in regions known as “tenia coli.” The myenteric plexus under the tenia is believed to be highly developed to control the adjacent large muscle mass, however, data on the innervation of this region are very scarce. We used whole mount preparations of human colon to characterize the organization of the myenteric plexus under the tenia coli (UT) and compared it with the plexus between the tenia (BT). Using histochemical staining for NADPH diaphorase, we found that the meshwork UT was 50% denser than BT, and that the ganglia UT were 30% wider. The density and size of the NADPH‐d positive neurons UT were similar to those of BT. We conclude that the myenteric plexus UT is considerably more developed than BT, and suggest to understand the control of colonic motility, the myenteric plexus UT needs to be further investigated. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.     

Increased risk for incisional hernia following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

Introduction

The incidence of incisional hernias (IH) after midline laparotomy varies from 11% to 20%. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is potentially prone to hernias because a Xiphoid to pubis laparotomy incision performed on patients who have undergone previous abdominal surgeries with the addition of chemotherapy and its related adverse effects.

Methods

We performed a retrospective analysis on a prospectively maintained single institution database from March 2015 to July 2020. The inclusion criteria were patients who underwent CRS-HIPEC and had at least 6 months postoperative follow-up with post-operative cross-sectional imaging study.

Results

Two hundred and one patients were included in the study. All patients underwent CRS-HIPEC with resection of previous scar and umbilectomy. Fifty-four patients were diagnosed with IH (26.9%). The major risk factors for IH in multivariate analysis were higher American society of Anesthesiologists score (ASA) (OR 3.9, P = 0.012), increasing age (OR 1.06, P = 0.004) and increasing BMI (OR 1.1, P = 0.006). Most of the hernia sites were median (n = 43, 79.6%). Eleven (20.4%) patients had lateral hernias due to stoma incisions or drain sites. Most of the median hernias were at the level of the resected umbilicus 58.9% (n = 23). Five (9.3%) of the patients with IH necessitated an urgent surgical repair.

Conclusion

We have demonstrated that more than a quarter of the patients after CRS-HIPEC suffer from IH and up to 10% of them may require surgical intervention. More research is needed to find the appropriate intraoperative interventions to minimize this sequela.     

Wellness of patients with chronic pain is not only about pain intensity

Objective

Attaining good outcomes in the management of chronic pain remains a clinical challenge. This study aimed to investigate the relationships between – and the contribution of – pain and related conditions to the wellness of these patients.

Design

A secondary analysis of database of patients with chronic pain treated with medical cannabis (MC) to carry out a one-year prospective follow-up study was conducted. Questionnaires were completed before (T₀), six (T₆), and twelve (T₁₂) months after MC initiation. Data included patients' demographics and questionnaires related to three latent factors: pain intensity measures, related conditions (catastrophizing, sleep disturbance, anxiety, and depression), and wellness parameters (quality-of-life, disability, subjective-health-state). Weighted average of the observed variables (WOBs) were calculated for each latent factor. Longitudinal structural equation modeling (SEM) and mediation analyses were performed to identify predictors and interrelations between the WOBs, respectively.

Results

Participants included 510 patients. All variables were significantly improved from T₀ to T₆ and T₁₂. SEM revealed that related conditions, and to a lesser extent pain, predicted wellness at T₀, T₆, and T₁₂ (related conditions: β₀ = 0.55, p < 0.001; β₆ = 0.54, p < 0.001; and β₁₂ = 0.51, p < 0.001; pain: β₀ = 0.42, p < 0.001; β₆ = 0.18, p < 0.001; and β₁₂ = 0.25, p < 0.001). Mediation analyses demonstrated that the effect of WOB-related conditions was greater than WOB-pain on wellness.

Conclusion

Wellness of patients with chronic pain can be determined not only by pain itself but even more so by the severity of related conditions. Thus, considering a broad spectrum of pain measures and related conditions seems relevant for improving the wellness of patients with chronic pain.