Chlorambucil-Loaded Graphene-Oxide-Based Nano-Vesicles for Cancer Therapy.

In this study, the authors have designed biocompatible nano-vesicles using graphene oxide (GO) for the release of chlorambucil (CHL) drugs targeting cancerous cells. The GO sheets were first sulfonated and conjugated with folic acid (FA) molecules for controlled release and high loading efficiency of CHL. The chlorambucil (CHL) drug loading onto the functionalized GO surface was performed through π-π stacking and hydrophobic interactions with the aromatic planes of GO. The drug loading and "in vitro" release from the nano-vesicles at different pH were studied. The average particle size, absorption, and loading efficiency (%) of FA-conjugated GO sheets (CHL-GO) were observed to be 300 nm, 58%, and 77%, respectively. The drug release study at different pH (i.e., 7.4 and 5.5) showed a slight deceleration at pH 7.4 over pH 5.5. The amount of drug released was very small at pH 7.4 in the first hour which progressively increased to 24% after 8 h. The rate of drug release was faster at pH 5.5; initially, 16% to 27% in the first 3 h, and finally it reached 73% after 9 h. These observations indicate that the drug is released more rapidly at acidic pH with a larger amount of drug-loading ability. The rate of drug release from the CHL-loaded GO was 25% and 75% after 24 h. The biotoxicity study in terms of % cell viability of CHL-free and CHL-loaded GO against human cervical adenocarcinoma cell line was found to have lower cytotoxicity of CHL-loaded nano-vesicles (IC50 = 18 µM) as compared to CHL-free (IC50 = 8 µM). It is concluded that a high drug-loading efficiency and controlled release with excellent biotoxicity of CHL-GO offers an excellent application in the biomedical field.

Atypical presentation of hairy cell leukemia: Significance of CD200 on flow cytometry.

Hairy cell leukemia (HCL) is a rare, low-grade mature B-cell neoplasm with a characteristic clinical, morphological, immunophenotypic, and more recently described molecular (BRAF p.V600E mutation) profile. It typically affects middle-aged to elderly male who present with pancytopenia and massive splenomegaly. Lymphadenopathy is usually not seen. Atypical presentations such as absence of splenomegaly and presence of lymphadenopathy and leukocytosis, a hypoplastic marrow masquerading as aplastic anemia, pose a diagnostic challenge to both clinician and pathologist. A diligent morphological examination to look for the presence of hairy cells along with flow cytometric immunophenotyping showing consistent bright expression of CD200, in addition to well-described characteristic immunophenotype, helps in correctly diagnosing the case. This can be further confirmed by the consistent presence of V600E point mutation in BRAF gene. The correct identification of HCL in these unusual clinical presentations is of utmost importance owing to a different treatment approach in these cases. We present here four such cases with atypical presentation.

Clinico-Pathological Spectrum and Novel Karyotypic Findings in Myelodysplastic Syndrome: Experience of Tertiary Care Center in India.

BACKGROUND: Myelodysplastic syndrome (MDS) is a heterogeneous disorder characterized clinically by the presence of cytopenia/s. Limited data are available about the morphological spectrum and cytogenetic profile of Indian MDS patients. The aim of the study was to ascertain the clinico-pathological, morphological and cytogenetic spectrum of Indian MDS patients. MATERIAL AND METHODS: A retrospective analysis of all patients diagnosed with MDS from June 2012 to December 2016 was performed. Their clinical and laboratory data were collated and reviewed. RESULTS: A total of 150 patients with primary MDS were evaluated with M: F ratio of 1.6:1 and the median age of 55.5 years. 64% patients presented with pancytopenia and 31% with bicytopenia. Morphologically they included MDS-MLD [63 (42%)], MDS-EB 2, [33 (22%)], MDS-EB 1 [32 (21.3%)], MDS-SLD [13 (8.6%)] and two cases (1.4%) each of MDS-SLD-RS, MDS-MLD-RS, and RCC. An abnormal cytogenetic profile was detected in 50% patients. Complex karyotype was observed to be the commonest abnormality (32.5%), and chromosome 7 was the most frequently involved chromosome. Isolated deletion 5q was seen in 6.9 % cases. Novel translocations like t(9;22)(q11.2;q34.2), t(1;5)(p22;q33), t(1;12)(p34;p11.2) and t(5;7;9)(q13;q32;p22) were observed in addition to other complex abnormalities. The majority of the patients belonged to the high risk IPSS-R prognostic groups (31.4%); followed by intermediate and very high-risk groups, 29% and 24.4% respectively. CONCLUSION: The median age of patients in India is a decade younger than the western population. Complex karyotype was observed to be the commonest cytogenetic abnormality, while the frequency of deletion 5q and trisomy 8 was much lower as compared to the west. The majority of the patients were in high to very high IPSS-R risk categories and seventy percent individuals below 40 years showed abnormal karyotype, indicating that Indian MDS patients have high disease burden at a young age and thus more likelihood for leukemic transformation.

A Novel Approach to Regain Anterior Space Using Modified 2 by 3 Fixed Appliance: A Report of Two Cases.

Early loss of permanent anterior teeth in growing children has a psychological impact on the child. Anterior teeth are important both aesthetically and functionally. When a permanent tooth is lost, the teeth adjacent to the created space tend to migrate into the space resulting in the space loss. Management of regaining space with the removable appliance always depends on child cooperation for using the appliance as well as for the recall visits. The advantages of fixed appliances over the removable appliances are minimal discomfort, reduced need for patient cooperation and increased control of tooth movements in all three directions of space. Thus, a short course of fixed appliance like the modified 2 by 3 fixed appliance followed by fixed functional space maintainer could be an ideal treatment option for such cases.