The genetics of psoriasis: a complex disorder of the skin and immune system

In the last few years, molecular genetics analyses have permitted novel insights into psoriasis, a disease characterized by uncontrolled proliferation of keratinocytes and recruitment of T cells into the skin. The disease affects approximately 1-2% of the Caucasian population and can occur in association with other inflammatory diseases such as Crohn's disease and in association with human immunodeficiency virus (HIV) infection. Given that psoriasis has characteristics of an autoimmune disease, it is not surprising that HLA studies revealed an association with certain alleles, notably HLA-Cw6. Despite this HLA component, psoriasis in some families is inherited as an autosomal dominant trait with high penetrance. Loci at chromosome 17q25 and 4q have been identified following genome-wide linkage scans of large, multiply affected families. In the case of at least the susceptibility locus at 17q25, the development of psoriasis does not require the presence of HLA-Cw6. Sib-pair analyses have confirmed the association with HLA-Cw6, confirmed the existence of a locus at 17q25 and identified other possible susceptibility loci. Two independent groups have reported a third region on chromosome 20p. Despite these findings, the extent of genetic heterogeneity and the role of environmental triggers and modifier genes is still not clear. The precise role of HLA also still needs to be defined. The isolation of novel susceptibility genes will provide insights into the precise biochemical pathways that control this disease. Such pathways will also reveal additional candidate genes that can be tested for molecular alterations resulting in disease susceptibility.      

Alterations in Lipid Metabolism and Antioxidant Status in Lichen Planus

Background:

Lichen planus (LP), a T-cell-mediated inflammatory disorder, wherein inflammation produces lipid metabolism disturbances, is linked to increase in cardiovascular (CV) risk with dyslipidemia. Increased reactive oxygen species and lipid peroxides have also been implicated in its pathogenesis.

Aim and Objective:

The aim of the study was to evaluate the status on lipid disturbances, oxidative stress, and inflammation in LP patients.

Materials and Methods:

The study was initiated after obtaining Institutional Ethics Committee permission and written informed consent from participants. The study included 125 patients (74 LP patients and 51 age and sex-matched controls) visiting the outpatient clinic in the dermatology department of our hospital. Variables analyzed included lipid profile, C-reactive protein (CRP), malondialdehyde (MDA), and catalase (CAT) activity.

Results:

Analysis of lipid parameters revealed significantly higher levels of total cholesterol (TC), triglycerides, and low-density lipoprotein cholesterol (LDL-C) along with decreased levels of high-density lipoprotein cholesterol (HDL-C) in LP patients as compared to their respective controls. LP patients also presented with a significantly higher atherogenic index that is, (TC/HDL-C) and LDL-C/HDL-C ratios than the controls. A significant increase in CRP levels was observed among the LP patients. There was a statistically significant increase in the serum levels of the lipid peroxidation product, MDA and a statistically significant decrease in CAT activity in LP patients as compared to their respective controls. A statistically significant positive correlation (r = 0.96) was observed between serum MDA levels and duration of LP whereas a significantly negative correlation (r = −0.76) was seen between CAT activity and LP duration.

Conclusion:

Chronic inflammation in patients with LP may explain the association with dyslipidemia and CV risk. Our findings also suggest that an increase in oxidative stress and imbalance in the antioxidant defense mechanisms in LP may play a role in the pathogenesis of LP.     

<Emphasis Type="Italic">Prakriti</Emphasis> (Ayurvedic concept of constitution) and variations in platelet aggregation

Background

Ayurveda, the Indian traditional system of medicine describes a unique concept “prakriti”, genetically determined, categorising the population into several subgroups based on phenotypic characters like appearance, temperament and habits. The concept is claimed to be useful in predicting an individual’s susceptibility to a particular disease, prognosis of that illness and selection of therapy. The present study was carried out to study if the platelet aggregatory response and its inhibition by aspirin varied in the different prakriti subtypes.

Methods

After obtaining Institutional Ethics Committee permission, normal healthy individuals of either sex between the age group 18 to 30 years were recruited in the study. Their prakriti evaluation was done using a standardized validated questionnaire (TNMC Prakriti 2004). Their Platelet Rich Plasma was incubated with either aspirin [2.5micro-mole (μM) and 5μM] or distilled water as control for three minutes after which the aggregatory response to 5μM Adenosine Diphosphate (ADP) was measured over a period of 7 minutes.

Results

We observed that in the study population of normal healthy participants (n= 137), ADP-induced maximal platelet aggregation (MPA) was highest among the Vata-pitta prakriti individuals [Median (range), 83.33% (52.33-96)] as compared to the other prakriti types and these individuals responded better to lower dose of aspirin compared to other prakriti types.

Conclusions

Our results suggest that identifying the prakriti may help in individualising therapy or predicting proneness to a disease.

     

Transient tone abnormalities in “high risk” infants and cognitive outcome at five years

Objective  

To identify transient tone abnormalities and determine its prevalence in “high risk” infants and their cognitive outcome at 5 years.     

Studies on the antibacterial action of novel gem-diphenyl-spiro-cyclopropano- oxazolones and 2-aryl(alkyl)-4-ylidene-oxazol-5-ones.

The preparation and in vitro antibacterial activity of a novel series of gem-diphenyl-spiro-cyclopropano-oxazolones (cis-1,2,2,5-tetraphenyl 6-oxa-4-azaspiro[2.4]hept-4-en-7-one) are described. The overall activity of these compounds was higher than that of the 2-aryl(alkyl)4-ylidene-oxazol-5-ones (azlactones). The gem-diphenyl-spiro-cyclopropano-oxazolones 1-4 have emerged as the most potent derivatives when tested against bacteria.     

A proposed ‘‘A to Z RAM (Radiograph Assessment Method)’’ for triage of patients with a suspected bone tumour

IntroductionWe propose a ‘‘A to Z RAM (Radiograph Assessment Method)’’ for evaluation of Radiograph of patients with a suspected bone tumour.MethodsIn the current study, ten radiological features with letters ‘A, B, C, D, E, F and Z’ were used and which included the age of the patient, involved part of the bone, characteristics, content, distinctiveness, the exterior of the bone, fracture, and zone of transition. Four independent observers (orthopaedic oncologists and surgical oncologists) evaluated a set of 30 radiographs of bone tumour selected at random from our hospital database based on A to Z RAM. We classified the lesions into two groups according to the traffic signal system; Green (suspected benign lesion) and Red (suspected malignant lesion).ResultsThere were 18 (60%) benign bone lesions and 12 (40%) malignant lesions in the current study. 91.6% of malignant tumours and 88.8% of the benign tumours were identified correctly by the four observers. The inter-observer variability with Fleiss kappa was 0.884 (95% CI 0.7–1.03 p-value < 0.05), suggestive of agreement not by chance. These radiographs were again reassessed by the four observers after 3 months. The interobserver variability by Fleiss kappa was 1.0 (95% CI 0.8–1.1) suggesting complete agreement amongst the observers. Both orthopaedic oncologists had intra-observer kappa as 1.0 each and both surgical oncologists had 0.795 and 0.930 respectively.ConclusionThe proposed A to Z RAM is an easy to use and reproducible method for reviewing radiographs in the out-patient department along with clinical findings for better management of patients with suspected bone lesions. The A to Z RAM can be a medical triage tool and subdivide bone lesions into two subgroups i.e. suspected benign lesion with a suggestion of further investigations with MRI and biopsy and suspected malignant lesion with a suggestion of MRI or early referral to a tertiary cancer center with expertise in orthopaedic oncology.Implications for practiceThe A to Z RAM (Radiologic Assessment Method) is a reproducible method for reviewing radiographs in the out-patient department and can be an aid for better management of patients.A to Z RAM is useful as a medical triage system, subdividing patients according to the probable diagnosis into a suspected benign lesion and suspected malignant lesion.