Infection in cirrhosis: A prospective study.

INTRODUCTION AND OBJECTIVES: Multidrug-resistant (MDR) infections in cirrhosis are associated with poor outcomes. We attempted a prospective study on infections in patients with cirrhosis evaluating microbiology of these infections and how outcomes depended on factors like bacterial resistance, appropriate antibiotics, stage of liver disease and whether outcomes were significantly different from patients who did not have infections. MATERIALS AND METHODS: This was a prospective evaluation involving one hundred and fifty nine patients with cirrhosis who were admitted at Peerless Hospitex Hospital and Research Center, Kolkata, West Bengal, India, during a 24 month period. One hundred and nineteen of these patients either had an infection at the time of admission or developed infection during hospitalization. Forty patients did not have an infection at admission and did not acquire infection while admitted. Data was collected about demographics, etiology of cirrhosis, liver and renal function and microbiology. RESULTS: Infections were community acquired in 27.7% of patients, healthcare associated in 52.9% and nosocomial in 19.3%. Gram negative bacilli (Escherichia coli 47.4% Klebsiella pneumoniae 23%) were common. 84.9% of enterobacteriaceae produced ESBL, AmpC or Carbapenemases. Spontaneous bacteria peritonitis (SBP) and urinary tract infection (UTI) were the most common sites of infection. In hospital mortality was 21.9%. Non-survivors had higher MELD (26 vs 19, p<0.001) and CTP scores (11.7 vs 10.3, p<0.001). The control group had lower MELD (16.65 vs. 20.8, p<0.001) and CTP scores (9.25 vs 10.59, p<0.001). CONCLUSIONS: MDR infections are common in patients with cirrhosis and have serious implications for treatment and outcomes.

Chitosan-heparin polyelectrolyte multilayers on cortical bone: periosteum-mimetic, cytophilic, antibacterial coatings.

Cortical bone allografts suffer from high rates of failure due to poor integration with host tissue, leading to non-union, fracture, and infection following secondary procedures. Here, we report a method for modifying the surfaces of cortical bone with coatings that have biological functions that may help overcome these challenges. These chitosan-heparin coatings promote mesenchymal stem cell attachment and have significant antibacterial activity against both S. aureus and E. coli. Furthermore, their chemistry is similar to coatings we have reported on previously, which effectively stabilize and deliver heparin-binding growth factors. These coatings have potential as synthetic periosteum for improving bone allograft outcomes.

Michler's Ketone: ß-Cyclodextrin Host-Guest Inclusion Complex for Enhancing the Ultraviolet Protection Factor of Poplin Cotton Fabric.

Michler's ketone (4,4' bis(N,N-dimethylamino)benzophenone) mk is a potential ultraviolet radiation (UVR) absorber in various materials. In this study, we have tested the UVR filtering ability of mk on cotton fabric. The beta-cyclodextrin (ß-CD) inclusion complex of mk enhances ultraviolet protection factor (UPF) drastically. The impact of ß-CD on the UVR filtering of mk are demonstrated by investigating the guest (mk:absorbers)-host (ß-CD:enhancer) inclusion complex. Spectral and molecular docking analysis of mk:ß-CD complex infers the vertical insertion of the guest molecule by positioning -C=O group of mk at the center of the host molecule with the exclusion of the terminal atoms of guest molecule outside the ß-CD cavity. Thus, the host; ß-CD renders an inflexible fit to the guest:mk. The inflexible fit of mk into the ß-CD cavity enhances the UVR dissipation when it is incorporated on the poplin cotton fabric. With UPF = 46 mk:ß-CD complex is proposed as a potential UVR absorber suitable for manufacturing sun protective textiles. The holding of mk by ß-CD enhances the UVR dissipation and hence facilitates the native red-shifted emission and non-radiative relaxation by the formation of twisted intramolecular charge transfer in mk.

Evaluation of the serum catalase and myeloperoxidase activities in chronic arsenic-exposed individuals and concomitant cytogenetic damage.

Chronic arsenic exposure through contaminated drinking water is a major environmental health issue. Chronic arsenic exposure is known to exert its toxic effects by a variety of mechanisms, of which generation of reactive oxygen species (ROS) is one of the most important. A high level of ROS, in turn, leads to DNA damage that might ultimately culminate in cancer. In order to keep the level of ROS in balance, an array of enzymes is present, of which catalase (CAT) and myeloperoxidase (MPO) are important members. Hence, in this study, we determined the activities of these two enzymes in the sera and chromosomal aberrations (CA) in peripheral blood lymphocytes in individuals exposed and unexposed to arsenic in drinking water. Arsenic in drinking water and in urine was used as a measure of exposure. Our results show that individuals chronically exposed to arsenic have significantly higher CAT and MPO activities and higher incidence of CA. We found moderate positive correlations between CAT and MPO activities, induction of CA and arsenic in urine and water. These results indicate that chronic arsenic exposure causes higher CAT and MPO activities in serum that correlates with induction of genetic damage. We conclude that the serum levels of these enzymes might be used as biomarkers of early arsenic exposure induced disease much before the classical dermatological symptoms of arsenicosis begin to appear.

Mutagenic, Genotoxic and Immunomodulatory effects of Hydroxychloroquine and Chloroquine: a review to evaluate its potential to use as a prophylactic drug against COVID-19.

Hydroxychloroquine (HCQ) and Chloroquine (CQ) are two anti-malarial drugs that are now being extensively used by front-line healthcare workers and other common people as a prophylactic drug against the Corona Virus Disease - 19 (COVID-19) in India and as well as in many parts of the world. While only a few in vitro studies have pointed to some efficacy of these drugs as a prophylactic against COVID-19, to date, there are no clinical studies that have established any clinical efficacy of these drugs as a prophylactic. These drugs are commonly used for the treatment of Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) because of its immunomodulatory effects. Previously, we have evaluated the genetic toxicology of different drugs and chemicals including antimalarial drug CQ both in vitro and in vivo. Thus, we recognize the need to critically review the mutagenic, genotoxic, and immunomodulatory effects of these drugs, to find out whether it is safe to use as a prophylactic drug against COVID-19. Existing literature suggests that CQ can induce mutagenic and genotoxic effects in multiple test systems and both the drugs have immunomodulatory effects. There was no data available to evaluate the mutagenicity and genotoxicity for HCQ. However, during metabolism about 60% of both the drugs remain unchanged and about 40% of the drugs are metabolized into two metabolites, desethylchloroquine and bisdesethylchloroquine by the action of the cytochrome P450 (CYP) enzymes in the liver. Both HCQ and CQ are immunomodulatory drugs and have the potential to suppress normal immune system activation. In this review, we have elucidated the mechanism of immunomodulation by both HCQ and CQ and highlighted the mutagenic and genotoxic effects from the available literature. This article is written with the sole objective that the reader will be able to recognize the adverse effects of these drugs when consumed by healthy individuals as a prophylactic. Current literature indicates that healthy individuals should refrain from the use of these drugs until further investigation.

An evaluation of UV protection imparted by cotton fabrics dyed with natural colorants.

BACKGROUND: The ultraviolet properties of textiles dyed with synthetic dyes have been widely reported in literature. However, no study has investigated the ultraviolet properties of natural fabrics dyed with natural colorants. This study reports the Ultraviolet Protection Factor (UPF) of cotton fabrics dyed with colorants of plant and insect origins. METHODS: Three cotton fabrics were dyed with three natural colorants. Fabrics were characterized with respect to fabric construction, weight, thickness and thread count. Influence of fabric characteristics on Ultraviolet Protection Factor was studied. Role of colorant concentration on the ultraviolet protection factor was examined via color strength analysis. RESULTS: A positive correlation was observed between the weight of the fabric and their UPF values. Similarly, thicker fabrics offered more protection from ultraviolet rays. Thread count appears to negatively correlate with UPF. Dyeing with natural colorants dramatically increased the protective abilities of all three fabric constructions. Additionally, within the same fabric type UPF values increased with higher depths of shade. CONCLUSION: Dyeing cotton fabrics with natural colorants increases the ultraviolet protective abilities of the fabrics and can be considered as an effective protection against ultraviolet rays. The UPF is further enhanced with colorant of dark hues and with high concentration of the colorant in the fabric.

On the relationship between fabric processing and ultraviolet radiation transmission.

BACKGROUND: The relationship between a fabric's physical characteristics and ultraviolet radiation transmission has been widely discussed in the literature. However, very few studies have taken into account the 'fiber-fabric construction-processing' history of fabrics into consideration to fully elucidate the ultraviolet (UV) protection abilities of fabrics. This study reports the effect of fabric processing treatments, both chemical and bio-chemical, on the transmission of UV radiation (UVR) through selected white and un-dyed fabrics. METHODS: Eight woven fabrics were selected to illustrate the effect of chemical processing on UVR transmission. Fabrics were characterized with respect to fiber chemistry, fabric construction, weight, thickness, and chemical processing history. Influence of fabric characteristics and processing on Ultraviolet protection factor (UPF) were studied. Furthermore, a knit bleached cotton T-shirt fabric was treated bio-chemically and the effect of bio-chemical processing on UPF was investigated. RESULTS: Physical characteristics of fabrics such as thickness, weight and cloth cover were shown to be only partly useful in explaining the UV protective abilities of fabrics in that the data show anomalies when only physical features of fabrics are considered without considering processing history. However, by taking into account the processing history of fabrics, the UPF values obtained can be fully explained. CONCLUSION: Chemical processing methods such as desizing and bleaching have a deleterious effect on UV transmission through fabrics. Bio-chemical processing such as the use of enzymes is comparatively benign and does not adversely impact the UV protective ability of cotton fabric.

Polymorphism in the ERCC2 codon 751 is associated with arsenic-induced premalignant hyperkeratosis and significant chromosome aberrations.

In West Bengal, India more than 6 million people are exposed to high levels of arsenic through drinking water. Since, only 15-20% of the exposed individuals show arsenic-induced skin lesions, it is assumed that genetic variation might play an important role in arsenic toxicity and carcinogenicity. Arsenic exposure often leads to the development of hyperkeratosis, the precursor of arsenic-induced skin cancer. ERCC2 (excision repair cross-complementing rodent repair deficiency, complementation group 2) is a nucleotide excision repair pathway gene, and its SNPs have been implicated in several types of epithelial cancers. We investigated the possible association of ERCC2 codon 751 A-->C polymorphism (lysine to glutamine) with arsenic-induced hyperkeratosis and correlated ERCC2 genotypes with increased frequencies of chromosomal aberration to ascertain whether any genotype leads to sub-optimal DNA repair. For this association study, 318 unrelated arsenic exposed subjects (165 with hyperkeratosis and 153 without any arsenic-induced skin lesions), drinking water contaminated with arsenic to a similar extent, were recruited. Genotyping was done through PCR-RFLP procedure. Lys/Lys genotype was significantly over-represented in the arsenic-induced hyperkeratosis-exhibiting group [odds ratio (OR) = 4.77, 95% confidence interval (CI) = 2.75-8.23]. A statistically significant increase in both CA/cell and percentage of aberrant cells was observed in the individuals with AA genotype compared to those with AC or CC genotype combined (P < 0.01) in each of the two study groups, as also, in the total study population. This study indicates that ERCC2 codon 751 Lys/Lys genotype is significantly associated with arsenic-induced premalignant hyperkeratosis and is possibly due to sub-optimal DNA repair capacity of the ERCC2 codon 751 Lys/Lys genotype.

Comparison of health effects between individuals with and without skin lesions in the population exposed to arsenic through drinking water in West Bengal, India.

A study was conducted to explore the effect of arsenic causing conjunctivitis, neuropathy and respiratory illness in individuals, with or without skin lesions, as a result of exposure through drinking water, contaminated with arsenic to similar extent. Exposed study population belongs to the districts of North 24 Parganas and Nadia, West Bengal, India. A total of 725 exposed (373 with skin lesions and 352 without skin lesions) and 389 unexposed individuals were recruited as study participants. Participants were clinically examined and interviewed. Arsenic content in drinking water, urine, nail and hair was estimated. Individuals with skin lesion showed significant retention of arsenic in nail and hair and lower amount of urinary arsenic compared to the group without any skin lesion. Individuals with skin lesion also showed higher risk for conjunctivitis ((odd's ratio) OR: 7.33, 95% CI: 5.05-10.59), peripheral neuropathy (OR: 3.95, 95% CI: 2.61-5.93) and respiratory illness (OR: 4.86, 95% CI: 3.16-7.48) compared to the group without any skin lesion. The trend test for OR of the three diseases in three groups was found to be statistically significant. Again, individuals without skin lesion in the exposed group showed higher risk for conjunctivitis (OR: 4.66, 95% CI: 2.45-8.85), neuropathy (OR: 3.99, 95% CI: 1.95-8.09), and respiratory illness (OR: 3.21, 95% CI: 1.65-6.26) when compared to arsenic unexposed individuals. Although individuals with skin lesions were more susceptible to arsenic-induced toxicity, individuals without skin lesions were also subclinically affected and are also susceptible to arsenic-induced toxicity and carcinogenicity when compared to individuals not exposed to arsenic.

Cytogenetic damage and genetic variants in the individuals susceptible to arsenic-induced cancer through drinking water.

In West Bengal, India, more than 300,000 arsenic-exposed people are showing symptoms of arsenic toxicity, which include cancers of skin and different internal organs. Since only 15-20% of the exposed population manifest arsenic-induced skin lesions, it is thought that genetic variation might play an important role in arsenic toxicity and carcinogenicity. A total of 422 unrelated arsenic-exposed subjects (244 skin-symptomatic and 178 asymptomatic) were recruited for this study. Cytogenetic damage, as measured by chromosomal aberrations in lymphocytes and micronuclei formation in oral mucosa cells, urothelial cells and binucleated lymphocytes, was studied in unexposed, skin-symptomatic and asymptomatic individuals with similar socioeconomic status. Identification of null mutations in GSTT1 and GSTM1 genes were carried out by PCR amplification. GSTP1 SNPs, implicated in susceptibility to various cancers, were assessed by PCR-RFLP method. Symptomatic individuals had higher level of cytogenetic damage compared to asymptomatic individuals and asymptomatic individuals had significantly higher genotoxicity than unexposed individuals. No difference in allelic variants in GSTT1 and GSTP1 was observed between these 2 groups. Incidence of GSTM1 null gene frequencies was significantly higher in the asymptomatic group. Individuals with GSTM1-positive (at least one allele) had significantly higher risk of arsenic-induced skin lesions (odds ratio, 1.73; 95% confidence interval, 1.24-2.22). These results show a protective role of GSTM1 null in arsenic toxicity. This study also indicates that asymptomatic individuals are sub clinically affected and are also significantly susceptible to arsenic-induced genotoxicity.