Micronucleus (MN) is a small additional nucleus and is readily identifiable by light microscopy. Biologically, micronuclei are the chromosome fragments or whole chromosomes that lag behind at anaphase during nuclear division. MN occurs due to genetic damage of the cell and the MN scoring is the indicator of the genetic damage. Therefore MN scoring can be used in various clinical setting such as to supervise genotoxicity, biomonitoring of diseases, screening of preneoplastic diseases and identification of high risk patients. In this brief review, the morphology, etiology, estimation, and applications of MN have been discussed.

Aims and Objectives: To score and compare micronucleus (MN) in the whole spectrum of cervical lesions including normal, inflammatory, abnormal squamous cell of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and invasive cancer (IC) and to evaluate the role of MN as a biomarker in different pre-neoplastic and neoplastic lesions. Materials and Methods: A total of 224 slides, comprised of normal (40), inflammatory (40), ASC-US (30), LSIL (38), HSIL (30) and IC (46), were studied. All the cases of HSIL, IC and ASC-US had histopathology. The LSIL, normal and inflammatory smears were again reviewed by 2 experienced cytopathologists independently. Two observers separately and independently counted the number of micronucleated cells per 1,000 of epithelial cells in oil immersion magnification (×100 objective) which was expressed as MN score per 1,000 cells. Results: The mean MN scores ± SD in normal, inflammatory, ASC-US, LSIL, HSIL and IC cases of cervical lesions were 1.02 ± 1.59, 0.4250 ± 0.71208, 2.87 ± 2.21, 4.7368 ± 5.62179, 21.30 ± 17.18 and 18.50 ± 9.54, respectively. MN scores of IC and HSIL were significantly high compared to the normal (p < 0.000), the inflammatory (p < 0.000), the ASC-US (p < 0.000) and to the LSIL (p < 0.000) group (analysis of variance test). LSIL showed significant difference with the normal (p = 0.043), the inflammatory (p = 0.019), the HSIL (p < 0.000) and the IC (p < 0.000) group but not with the ASC-US (p = 0.342) group. Conclusions: MN scoring on the epithelial cells of cervix could be used as a biomarker in cancer screening. This is an easy, simple, reliable, reproducible and objective test which can be performed on routinely stained smears.

Lopinavir (LVR) is extensively metabolized by CYP3A4 and is prevented from entering the cells by membrane efflux pumps such as P-gp and MRP2. In an approach to evade the first-pass metabolism and efflux of LVR, peptide prodrugs of LVR [valine-valine-lopinavir (VVL) and glycine-valinelopinavir (GVL)] were synthesized. Prodrugs were identified with 1 H and 13 C NMR spectra and LC/ MS/MS was employed to evaluate their mass and purity. Solubility studies indicated that the prodrugs have much greater solubility as compared with LVR in water. In vitro evaluations were performed to determine affinities for efflux proteins (P-gp and MRP2) and CYP3A4 and permeabilities across intestinal barrier. Accumulation and transport data of VVL and GVL across MDCKII-MDR1 and MDCKII-MRP2 cells indicated evasion of prodrugs' efflux by P-gp and MRP2 significantly. Permeability studies across Caco-2 cells indicated that the prodrugs are transported by peptide transporters and have increased permeability as compared with LVR. VVL and GVL exhibited significantly better degradation rate constants as compared with LVR in rat liver microsomes. Enzymatic stability studies in Caco-2 cell homogenate indicated that the peptide prodrugs are first converted to the ester intermediate and then finally to the parent drug. Overall, the advantages of utilizing peptide prodrugs include chemical modification of the compound to achieve targeted delivery via peptide transporters present across the intestinal epithelium, significant evasion of efflux and CYP3A4 mediated metabolism and significantly better solubility profiles. Therefore, in vitro studies demonstrated that peptide prodrug derivatization of LVR may be an effective strategy for bypassing its efflux and enhancing its systemic bioavailability.

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SummaryOculocutaneous albinism (OCA) is a heterogeneous group of autosomal recessive disorders characterized by an abnormally low amount of melanin in the eyes, skin and hair, and associated with common developmental abnormalities of the eye. Defects in the tyrosinase gene (TYR) cause a common type of OCA, known as oculocutaneous albinism type 1 (OCA1). The molecular basis of OCA has been studied extensively in different population groups, but very little information is available on Indian patients. Our investigation covering thirteen ethnic groups of India, some representing >20 million people, revealed that among 25 OCA families 12 were affected with OCA1, and that these cases were primarily due to founder mutations in TYR. We detected nine mutations and eight SNPs in TYR, of which six mutations (five point mutations & one gross deletion) were novel. In contrast to most reports describing compound heterozygotes, the presence of homozygotes in 10 out of the 12 pedigrees underscores the lack of intermixing between these ethnic groups in India. Haplotype analysis suggested a few founder chromosomes causing the disease in the majority of the patients. Direct detection of the mutations prevalent in specific ethnic groups could be used for carrier detection and genetic counselling.

SMVT was identified and functionally characterized on ARPE-19 cells. Further, Biotin-GCV shares this transport system. Vitreal pharmacokinetics of the conjugate was determined in unconscious rabbit model.

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MN scoring on routinely stained smears of IDCs was significantly higher than in fibroadenoma and was relatively easy, reliable and reproducible. As MN scoring of grade 1 IDC was similar to fibroadenoma, a larger study should be conducted to compare grade 1 IDC with other benign breast lesions.