Effects of prednisolone treatment on cytokine expression in patients with leprosy type 1 reactions

Leprosy type 1 reactions (T1R) are due to increased cell-mediated immunity and result in localized tissue damage. The anti-inflammatory drug prednisolone is used for treatment, but there is little good in vivo data on the molecular actions of prednisolone. We investigated the effect of prednisolone treatment on tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-10, and transforming growth factor beta1 (TGF-beta1) mRNA and protein expression in blood and skin biopsies from 30 patients with T1R in India. After 1 month of prednisolone treatment the sizes of the skin granulomas were reduced, as were the grades of cells positive for TNF-alpha and IL-10 in skin lesions. Increased production of TGF-beta1 was seen in skin lesions after 6 months of prednisolone treatment. Expression of mRNA for TNF-alpha, IL-1beta, and TGF-beta1 was reduced, whereas no change in IL-10 mRNA expression was detected during treatment. The circulating cytokine profiles were similar in patients with and without T1R, and prednisolone treatment had no detectable effects on cytokine expression in the blood. The data emphasize the compartmentalization of pathology in T1R and the importance of the immune response in the skin. Clinical improvement and cytokine expression were compared. Surprisingly, patients with improved skin and nerve function and patients with nonimproved skin and nerve function had similar cytokine profiles, suggesting that clinical improvement is not directly mediated by the cytokines studied here. This in vivo well-controlled study of the immunosuppressive effects of prednisolone showed that the drug does not switch off cytokine responses effectively.     

Segmental jejunal lipomatosis--a rare cause of intestinal obstruction

A rare case of a segmental small intestinal (jejunal) lipomatosis is described. A 33-year-old male was admitted with a clinical diagnosis of an acute intestinal obstruction. A plain erect abdominal x-ray showed multiple air-fluid levels. On an exploratory laparotomy, a jejunojejunal intussusception was found secondary to a segmental submucosal lipomatosis. This was treated by a segmental resection and anastomosis, which resulted in a complete cure. Here we present this case with a review of the relevant literature.     

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.     

Identification and Characterization of Edible Cricket Peptides on Hypertensive and Glycemic In Vitro Inhibition and Their Anti-Inflammatory Activity on RAW 264.7 Macrophage Cells

Recent studies continue to demonstrate the potential of edible insects as a protein base to obtain bioactive peptides applicable for functional food development. This study aimed at identifying antihypertensive, anti-glycemic, and anti-inflammatory peptides derived from the in vitro gastrointestinal digests of cricket protein hydrolysates. After sequential fractionation, the protein digest subfraction containing the lowest molecular weight (<0.5 kDa), hydrophobic (C18) and cationic peptides (IEX) was found responsible for the most bioactivity. The cationic peptide fraction significantly reduced (p < 0.05) α-amylase, α-glucosidase, and angiotensin converting enzyme (ACE) activity in vitro, and also inhibited the expression of NF-κB in RAW 264.7 macrophage cells. A total of 28 peptides were identified with mass spectrometry (LC–MS/MS) and de novo sequencing from the potent fraction. Three novel peptides YKPRP, PHGAP, and VGPPQ were chosen for the molecular docking studies. PHGAP and VGPPQ exhibited a higher degree of non-covalent interactions with the enzyme active site residues and binding energies comparable to captopril. Results from this study demonstrate the bioactive potential of edible cricket peptides, especially as ACE inhibitors.     

Association of IL‐1β +3954 C/T and IL‐10‐1082 G/A Cytokine Gene Polymorphisms with Susceptibility to Tuberculosis

Tuberculosis (TB) constitutes the major cause of death due to infectious diseases. Cytokines play a major role in defence against Mycobacterium tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Household contacts (HHC) are at increased risk of developing the disease. In this study, we examined the association of IL‐1β and IL‐10 cytokine gene polymorphisms with risk of developing tuberculosis in TB patients, their HHC and healthy controls (HC) using JavaStat and SPSS. Multifactor dimensionality reduction (MDR) analyses were performed to explore the potential gene–gene interactions. The genotype and allele frequencies of IL‐1β +3954C/T polymorphism did not vary significantly between TB patients and HC. GG (P < 0.005, OR = 0.219 and 95% CI = 0.059–0.735) and GA (P < 0.0001, OR = 2.938 and 95% CI = 1.526–5.696) genotypes of IL‐10‐1082 G/A polymorphism were found to be significantly associated with patients versus HC. HHC with CC (P < 0.03, OR = 1.833 and 95% CI = 1.1–3.35) genotype in IL‐1β and GA (P < 0.0001, OR = 4.612 and 95% CI = 2.225–9.702) genotype in IL‐10 were at increased risk of developing tuberculosis. MDR tests revealed high‐risk genotypes in IL‐1β and IL‐10 based on the association model. Our results demonstrate that the polymorphisms of IL‐1β and IL‐10 genes may be valuable markers to predict the risk for the development of TB in household contacts.     

Reporting of dose–volume specifications for “Martinez Universal Perineal Interstitial Template–based interstitial high-dose-rate brachytherapy for gynecological cancers” according to International Commission on Radiation Units and Measurements 58 with early clinical outcomes

PurposeThe study is an audit of reporting dose and volume specifications as per the ICRU 58 for MUPIT-based interstitial brachytherapy in gynecological cancers. Correlation between total reference air kerma (TRAK) and isodose surface was also evaluated to understand the intensity of treatment in interstitial brachytherapy.Methods and MaterialsForty-two patients underwent HDR MUPIT-based interstitial brachytherapy 20 Gy in five fractions after EBRT during 2017–2019. Treated volume, high and low-dose regions, mean central dose, Dose Homogeneity Index (DHI), organ at risk doses, and TRAK values were computed.ResultsHigh-dose regions V150 mean was 12.4 cc and V200 was 4.58 cc; and low-dose region was 75.92 cc. The mean treated volume was 59.8 cc. The mean central dose was 3.7 Gy. DHI was 79%. The mean D2cm³ bladder and rectum were 2.9 Gy and 2.8 Gy. The mean TRAK was 0.16 cGy per fraction per hour at 1 m. TRAK values showed significant correlation with various isodose volumes (TRAK and V100: r = 0.943 p < 0.0005; and TRAK and V50: r = 0.953; p < 0.0005). A positive correlation was observed between TRAK and the number of needles (r = 0.746; p < 0.0005). At a median followup of 16 months, 4 of 42 patients (9.5%) had local recurrences.ConclusionsOur study shows compliance with ICRU 58 recommendations along with certain deviations. Local recurrence rate is acceptable. TRAK shows correlation with surface isodose in MUPIT-based brachytherapy and should to be evaluated in future studies.     

Influence of anti‐inflammatory irrigant on substance P expression for single‐visit root canal treatment of teeth with irreversible pulpitis

One of the main objectives of root canal treatment is to alleviate the pain associated with irreversibly inflamed pulps. However, some patients may have moderate to severe pain following treatment. The aim of this study was to compare and assess the effect of ketorolac tromethamine on substance P expression in the pulp and periapical tissues when used as a root canal irrigant for single‐visit root canal treatment in teeth with irreversible pulpitis. Thirty‐six patients were randomly allotted to three irrigant groups – saline (n = 14), 3% sodium hypochlorite (n = 11) and ketorolac tromethamine (n = 11). Pulp blood samples (S1) were collected on gaining access to the pulp, and periapical blood samples (S2) were collected after root canal preparation. Quantification of substance P was done by ELISA test. The ketorolac tromethamine group had greater reduction in substance P expression (S2). Post‐operative pain levels were not significantly influenced by the different root canal irrigants.     

Efficacy of Peracetic Acid in Rapid Disinfection of Resilon and Gutta-percha Cones Compared with Sodium Hypochlorite,Chlorhexidine, and Povidone-iodine

Background

The aim of this investigation was to compare the effectiveness of 3% sodium hypochlorite (NaOCl), 2% chlorhexidine, 1% peracetic acid, and 10% povidone-iodine in the rapid disinfection of Resilon (Pentron Clinical Technologies, LLC, Wallingford, CT) and gutta-percha cones contaminated with Enterococcus faecalis and Bacillus subtilis.

Methods

Two hundred fifty-six samples consisting of 128 gutta-percha cones and 128 Resilon cones were used in this study. The materials were tested for disinfection according to the type of solution (3% NaOCl, 2% chlorhexidine, 1% peracetic acid, or 10% povidone-iodine), the time of exposure to each solution (1 or 5 minutes), and the type of microorganisms (E. faecalis or B. subtilis). Subsequent to the disinfection, samples were placed in test tubes containing 10 mL Mueller-Hinton broth and incubated at 37°C for 7 days. All test tubes were observed at 24-hour intervals and visually checked for turbidity, signifying microbial growth.

Results

In this study, 1% peracetic acid showed the best results for both 1 minute and 5 minutes of disinfection, 2% chlorhexidine showed the second best results although it was statistically at par with peracetic acid, and 3% hypochlorite ranked third in disinfection; this was statistically significant when compared with peracetic acid and chlorhexidine. Disinfection by povidone-iodine was the least within all the groups for both contact times although disinfection for 5 minutes showed better results than disinfection for 1 minute for gutta-percha.

Conclusions

The outcome of this study confirmed the efficacy of 1% peracetic acid and 2% chlorhexidine in the rapid disinfection of both Resilon and gutta-percha.     

Transradial Szabo Technique for Intervention of Ostial Lesions

Objectives: The aim of our study is to assess the feasibility and safety of transradial intervention (TRI) of coronary ostial lesions using the Szabo technique. Background: When performing TRI of coronary ostial lesions, precise stent positioning is of paramount importance. TRI has experienced increasing popularity in the U.S.; however, utilization of the Szabo technique has not been systematically evaluated in this setting. We report the results of ostial stent deployment using the Szabo technique for 2 experienced TRI operators and centers. Methods: This was a retrospective analysis of 40 consecutive patients who underwent PCI from April 2009 to September 2011. All patients who underwent PCI via the transradial route with the Szabo technique for ostial lesions performed by experienced transradial operators (>200 cases/yr) were included. Results: In our study of 40 patients with 41 coronary ostial lesions, overall procedural success rate was 100%. Stent dislodgement was seen in 1 patient. Clinical follow up was 100%, with a mean duration of 292.7±200 days. Target lesion revascularization (TLR) was seen in 2 patients (5%). One patient had an episode of transient ischemic attack (TIA) at 33 days after PCI; another experienced subacute stent thrombosis at 81 days while on dual antiplatelet therapy. MACE was 7.5% overall. Conclusion: In our study, treatment of coronary ostial lesions with the Szabo technique via TRI is associated with a high procedural success rate and a low MACE of 7.5%. (J Interven Cardiol 2012;25:447-451).     

Representative Scale-Down Lyophilization Cycle Development Using a Seven-Vial Freeze-Dryer (MicroFD®)

We have implemented the use of a small-scale, 7-vial Micro Freeze Dryer (MicroFD^®; Millrock Technology, Inc.) that has the capability to accurately control heat transfer during lyophilization. We demonstrate the ability to fine-tune the MicroFD^® vial heat transfer coefficient (K_v) to match the K_v of vials in a LyoStar III laboratory-scale unit. When the MicroFD^® is run under conditions that match the K_v of the LyoStar III, the resulting lyophilization performance between scales results in equivalent product temperature profiles and critical quality attributes for the same drying process. The proposed workflow demonstrates how exploitation of K_v control in the MicroFD^® enables cycle development of at-scale lyophilization processes using only 7 product vials. By changing the MicroFD^® K_v, laboratory and, potentially, manufacturing cycles may be simulated using only 7 product vials for tremendous active pharmaceutical ingredient savings, as long as at-scale heat transfer coefficients are well characterized.