Gallic acid, an antioxidant, exhibits antiapoptotic potential in normal human lymphocytes: A Bcl-2 independent mechanism

Oxidative stress, produced as a consequence of normal metabolism or induced by extraneous stimuli, has been proved to be a mediator of cell death. The inherent antioxidant defense system and exogenous antioxidants can help the body to combat this oxidative stress-induced cell death. In this study, we explored the antiapoptotic potential of gallic acid, a dietary phenolic having antioxidative and anticarcinogenic properties, in normal human peripheral blood lymphocytes (PBLs). Incubation of PBLs with 100 microM H2O2 for 1.5-2.0 h induced phosphatidyl serine externalisation, lipid peroxidation and high molecular weight DNA fragmentation. Pretreatment of lymphocytes with gallic acid for 18 h could effectively inhibit lipid peroxidation and apoptosis induced by oxidative stress. Treatment of PBLs with gallic acid failed to induce any change in the expression of Bcl-2, an antiapoptotic protein. It seems that the protection provided by gallic acid was due to its direct action in the scavenging of free radicals as it was found to be a stronger antiradical than trolox, a water- soluble analogue of vitamin E.     

Study of multidrug therapy in paucibacillary leprosy

A study was undertaken to evaluate the efficacy of multidrug therapy (MDT) in paucibacillary leprosy. Out of 155 fresh cases studied 48 had indeterminate, 38 tuberculoid and 69 had borderline tuberculoid leprosy. Out of 155 cases, 64 patients in the first group were treated with dapsone 100 mg daily for 12 months. In the second group, 91 patients were given MDT, consisting of rifampicin 600 mg once a month and dapsone 100 mg daily for consecutive 12 months. The cases receiving dapsone and the cases having MDT remained clinically active at the end of 6 months in 56.1% and 37.2% respectively; 13.1% of cases having single lesion and 66.3% of patients with multiple lesions were found to be active after 6 months of MDT. At the end of one year 79.6% cases receiving dapsone and 91.2% cases having MDT became inactive.     

Heat shock improves recovery and provides protection against global ischemia after hypothermic storage

Background. Improved methods of donor heart preparation before preservation could allow for prolonged storage and permit remote procurement of these organs. Previous studies have shown that overexpression of heat-shock protein 72 provides protection against ischemic cardiac damage. We sought to determine whether rats subjected to heat stress with only 6-hour recovery could acquire protection to a subsequent heart storage for 12 hours at 4°C.

Methods. Three groups of animals (n = 10 each) were studied: control, sham-treated, and heat-shocked rats (whole-body hyperthermia 42°C for 15 minutes). After 12-hour cold ischemia hearts were reperfused on a Langendorff column. To confirm any differences in functional recovery, hearts were then subjected to an additional 15-minute period of warm global ischemia after which function and lactate dehydrogenase enzyme leakage were measured.

Results. Heat-shocked animals showed marked improvements compared with controls in left ventricular developed pressure (63 ± 4 mm Hg versus 44 ± 4 mm Hg, p < 0.05) heart rate × developed pressure (13,883 ± 1,174 beats per minute × mm Hg versus 8,492 ± 1,564 beats per minute × mm Hg, p < 0.05), rate of ventricular pressure increase (1,912 ± 112 mm Hg/second versus 1,215 ± 162 mm Hg/second, p < 0.005), rate of ventricular pressure decrease (1,258 ± 89 mm Hg/second versus 774 ± 106 mm Hg/second, p < 0.005). Diastolic compliance and lactate dehydrogenase release were improved in heat-shocked animals compared with controls and sham-treated animals. Differences between heat-shocked animals and control or sham-treated animals were further increased after the additional 15-minute period of warm ischemia. Western blot experiments confirmed increased heat-shock protein 72 levels in heat-shocked animals (> threefold) compared with sham-treated animals and controls.

Conclusions. Heat shock 6 hours before heart removal resulted in marked expression of heat-shock protein 72 and protected isolated rat hearts by increased functional recovery and decreased cellular necrosis after 12-hour cold ischemia in a protocol mimicking that of heart preservation for transplantation. Protection was further confirmed after an additional 15-minute period of warm ischemia.     

Allergenic nature of Parthenium hysterophorus

Parthenin has been reported as the active allergen in Parthenium hysterophorus contact sensitivity. A study was carried out to test various chemical fractions of the plant for isolating and identifying the exact allergens. Two additional sesquiterpene lactones apart from parthenin have been shown to be allergenically active. Structures of these sesquiterpenoids are presented. Photopatch tests do not indicate a photosensitizing capacity for these compounds.     

Crystallization of a complex between the Fab fragment of a human immunoglobulin M (IgM) rheumatoid factor (RF-AN) and the Fc fragment of human IgG4.

Rheumatoid factors (RF) are the characteristic autoantibodies found in patients with rheumatoid arthritis. They recognize epitopes in the Fc region of immunoglobulin G (IgG) and are often of the IgM isotype. In order to analyse the nature of RF-Fc interactions, we have crystallized a complex between the Fab fragment of a human monoclonal IgM rheumatoid factor (RF-AN) and the Fc fragment of human IgG4. The stoichiometry of the complex within the crystals was found to be 2:1 Fab:Fc. The crystals diffracted X-rays to 0.3 nm resolution, and the space group was C2, with cell dimensions a = 16.03 nm, b = 8.19 nm, c = 6.42 nm, beta = 98.3 degrees. We have also determined the sequence of the variable region of the RF-AN light chain, not hitherto reported. This belongs to the V lambda III-a subgroup and is closely related to the germline gene Humlv318, from which it differs in three amino acid residues. This is the first reported crystallized complex between a human autoantibody and its autoantigen.     

Changes in alcohol use during the COVID-19 pandemic and previous pandemics: A systematic review

The objective of this study is to summarize the research on the relationships between exposure to the COVID-19 pandemic or previous pandemics and changes in alcohol use. A systematic search of Medline and Embase was performed to identify cohort and cross-sectional population studies that examined changes in alcohol use during or following a pandemic compared to before a pandemic occurred. Outcomes examined included differences in the volume and frequency of alcohol consumption and the frequencies of heavy episodic drinking (HED) and alcohol-related problems during a pandemic compared to before a pandemic. Quality assessment was performed using the Cochrane Risk of Bias Tool for Nonrandomized Studies. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search yielded 672 articles; 27 were included in the narrative review, of which 6 were cohort studies (all from high-income countries). A total of 259,188 participants were included. All cohort studies examined the impact of COVID-19 and associated pandemic-related policies, including social distancing and alcohol-specific policies, on alcohol use. Cohort studies demonstrated a consistent significant decrease in total alcohol consumption (Australia) and a significant increase in the frequency of alcohol use (United States). A significant decrease in the frequency of HED was observed in Australia and Spain but not in the United States. A significant increase in the proportion of people with problematic alcohol use was observed in the United Kingdom. Initial insights into changes in alcohol use indicate substantial heterogeneity. Alcohol use may have decreased in some countries, while HED and the proportion of people with problematic alcohol use may have increased. The lack of high-quality studies from low- and middle-income countries reflects a dearth of information from countries inhabited by most of the world's population.     

The determination of the human ventricular gradient from body surface potential map data

We have analyzed the Wilson ventricular gradient in terms of body surface potential maps and of the reduction of such surface patterns to equivalent dipoles or vectors. While the ventricular gradient traditionally was treated as first a scalar, then a vector concept, we found that the three entities (QRS area, T area, QRST area) did not reduce to vectors with a common location. However, conventional vector addition (QRST area = QRS area + T area) did precisely apply. Further we found considerable more-than-vector or extra-dipolar information remaining for all three entities after removal of the dipole effect. This suggests that maps of these entities should be considered the boundaries of complex electrical fields rather than simple surface effects of vectors.     

Aortic cusp involvement causing severe aortic regurgitation in a case of relapsing polychondritis

A case with relapsing polychondritis is described where primary involvement of the aortic valve cusps produced severe aortic regurgitation requiring valve replacement. An aneurysmal dilatation of the ascending aorta developing later led to disruption of the prosthesis requiring re-operation. Superior vena caval obstruction, an abdominal aortic aneurysm which ruptured and required resection, and obstructive lesions in common iliac arteries, presumably the result of the same process that involved the aorta and the cartilaginous structures, were also seen.