Molecular studies in familial dilated cardiomyopathy - A pilot study.

Aim: To study genetic variants in patients of familial dilated cardiomyopathy. Methodology: Patients with reduced ejection fraction of less than 45% and dilated left ventricle are considered to have dilated cardiomyopathy. Clinical history was taken and possible secondary causes of dilated cardiomyopathy were excluded. Family history of ≥2 affected relatives or sudden cardiac death in a relative with age less than 35 years were included. Such patients blood sample were sent for next generation sequencing and analysed for presence of genetic variants. Results: As part of pilot study 20 patients (44% were female and 66% were male) were included. There was presence of 16 different pathogenic variants in 14 patients. Two patients had more than one variants in them. Most common of which were sarcomeric mutations constituting 32%. Titin followed by Filamin, Lamin and Desmosomal where the most commonly repeated mutations. Discussion: In our patients of familial dilated cardiomyopathy, 70% were detected to have pathogenic variants in them. Most common variations were seen on Titin gene. Thus those with familial dilated cardiomyopathy should be considered for next generation sequencing. First degree relatives of those with pathogenic variants should be screened using cascade testing for earlier detection and disease monitoring in them.

Effect of Yoga Lifestyle in Patients with Heart Failure: A Randomized Control Trial.

Background: In spite of significant advances in the management of heart failure (HF), morbidity and mortality remain high. Therefore, there is a need for additional strategies. We did a randomized clinical trial to study effect of yoga in patients with HF in terms of quality of life (QOL), left ventricle ejection fraction (LVEF), C-reactive protein (CRP), and NTproBNP. Materials and Methods: 60 patients with stable HF New York Heart Association Class II with LVEF 30%-40% were randomized into control group (CG) and yoga group (YG). CG received the guideline-based therapy and YG in addition practiced the yoga, one hour daily for 3 months. All patients were assessed for QOL, CRP, NTProBNP, and LVEF at baseline and after 3 months. Results: A significant difference was observed in all four parameters in the YG as compared to the CG (P < 0.01) after 12 weeks. QOL as assessed by Minnesota living with heart failure questionnaire score improved significantly in YG as compared to CG (10 V/s 14, P < 0.001). There was a significant improvement within YG in terms of LVEF (33.4-36.8, P = 0.001), and the percentage change in LVEF was significant between the groups (10% V/s 5%, P = 0.001). NTproBNP also significantly reduced by 69.8% from 755 to 220 Pmol/l in YG as compared to 39.3% in CG (679-406 Pmol/l). CRP decreased by 49.3% (5.36-2.73 mg/L) in YG and 35.8% (5.39-3.45 mg/L) in CG. Conclusion: The result of this pilot study suggests that addition of yoga to guideline-based therapy for HF patients significantly improves QOL, LVEF, and NTProBNP and reduces CRP level. Larger studies are needed to confirm these findings.

Hyaluronic acid conjugated multi-walled carbon nanotubes for colon cancer targeting.

Purpose of the present research was to evaluate in vitro and in vivo potential of gemcitabine (GEM) loaded hyaluronic acid (HA) conjugated PEGylated multi-walled carbon nanotubes (GEM/HA-PEG-MWCNTs) for effective colon cancer targeting. HA was conjugated onto the surface of aminated or PEGylated MWCNTs which were evaluated for size, surface morphology, entrapment efficiency (~90%), in vitro drug release, in vitro cytotoxicity and in vivo performance in Sprague Dawley rats. In vitro release showed that the release rate of GEM in acidic conditions (pH 5.3) was faster than physiological conditions (PBS, pH 7.4) followed by a sustained release pattern. The developed GEM/HA-PEG-MWCNTs indicated significantly less hemolytic toxicity (7.73 ±â€¯0.4%) paralleled to free GEM (18.71 ±â€¯0.44%) and showed higher cytotoxicity against HT-29 colon cancer cell line. The antitumor study assured that GEM/HA-PEG-MWCNTs significantly reduced tumor volume as compared to free GEM and increased survival rate without noticeable loss in body weight. In vivo studies showed an improvement in pharmacokinetics in terms of remarkable escalation in mean residence time, half-life, AUC, AUMC, median survival time in tumor bearing rats treated with GEM/HA-MWCNTs and GEM/HA-PEG-MWCNTs as compared to free GEM (p ˂ 0.001). These outcomes proved engineered MWCNTs as a safe and effective nanomedicine in colon cancer targeting.

Mannosylated solid lipid nanoparticles for lung-targeted delivery of Paclitaxel.

OBJECTIVE: The present study discusses paclitaxel (PTX)-loaded mannosylated-DSPE (Distearoyl-phosphatidyl-ethanolamine) solid lipid nanoparticles (M-SLNs) using mannose as a lectin receptor ligand conjugate for lung cancer targeting and to increase the anticancer activity of PTX against A549 lung's epithelial cancer cells. MATERIALS AND METHODS: The PTX-SLNs were prepared by solvent injection method and mannose was conjugated to the free amine group of stearylamine. The M-SLNs obtained were characterized for their particle size, polydispersity index, zeta potential and morphology by transmission electron microscope. RESULTS: The M-SLNs were spherical in shape with 254 ± 2.3 nm average size, positive zeta potential (3.27 mV), 79.4 ± 1.6 drug entrapment efficiency and showed the lower extent of drug release 40% over 48 h in vitro. Cytotoxicity study on A549 cell lines and biodistrubtion study of drug revealed that M-SLNs deliver a higher concentration of PTX as compared to PTX-SLNs in an alveolar cell site. DISCUSSION AND CONCLUSION: These results suggested that mannosylated M-SLNs are safe and potential vector for lung cancer targeting.

Folate-conjugated albumin nanoparticles for rheumatoid arthritis-targeted delivery of etoricoxib.

OBJECTIVE: The present study discusses folic acid-etoricoxib-bovine serum albumin nanoparticles (F-ETX-NPs) using folic acid as an over expressed folate receptor ligand for activated macrophages in targeting of rheumatoid arthritis. MATERIALS AND METHODS: For this purpose etoricoxib-loaded BSA nanoparticles (ETX-NPs) were prepared by desolvation method and activated folic acid conjugation with free amine group of BSA was confirmed by FTIR study and zeta potential measurements. RESULTS: The F-ETX-NPs showed spherical in shape with 215.8 ± 3.2 nm average size + 7.8 mV zeta potential, 72 ± 1.3% etoricoxib entrapment efficiency and showed 93.1 ± 2.2% cumulative etoricoxib release upto 72 h. The etoricoxib concentration from F-ETX-NPs was found to be 9.67 ± 0.34 µg/g in inflamed joint after 24 h administration revealed remarkably targeting potential to the activated macrophages cells and keep at a high level during the experiment. DISCUSSION AND CONCLUSION: These results suggest that F-ETX-NPs are potentially vector for activated macrophages cells targeting of rheumatoid arthritis.

Development and characterization of nanolipobeads-based dual drug delivery system for H. pylori targeting.

The objective of the present investigation was to prepare and evaluate nanolipobeads which permit the targeting of drugs to H. Pylori and potentially used for the treatment of gastric ulcer. For this polyvinyl alcohol nanoparticles were prepared by freeze thaw cyclizing method and surface acylation was done by treating with (1M) palmitoyl chloride in hexane followed by addition of 0.1 N NaOH to induce acylation by adjusting pH below 6.5. Finally, nanolipobeads synthesis was carried out by combining equal parts of suspension of acylated poly vinyl alcohol nanoparticles (PVA-NPs) and AMOX encapsulated PE liposomes suspension. The uniformity of supported PE lipid layer on acylated PVA-NPs was examined using fluorescence and confocal laser scanning electron microscopy. The optimized nanolipobeads formulation demonstrated 773.3 ± 4.3 nm average age size and 84.7 ± 2.9% of AMOX and 67.5 ± 2.8% of RBC release up to 72 h, respectively. Furthermore, binding specificity and targeting propensity toward H. pylori (SKP-56) was confirmed by agglutination and in situ adherence assay. Reduction of the absolute alcohol induced ulcerogenic index from 3.01 ± 0.25 to 0.31 ± 0.09 and 100% H. pylori clearance rate was observed. These results suggested that nanolipobeads are potential vector for development of dual drug delivery for effective treatment of H. pylori associated peptic ulcer.

Amlodipine- induced gingival overgrowth: a case report.

Drug-induced gingival overgrowth occurs in genetically susceptibIe individuals as a side effect of various drugs. There is a gross disfiguring enlargement of gingiva mostly in the anterior region leading to difficulty in mastication, speech and maintenance of oral hygiene. In this case report, amlodipine-induced gingival enlargement and its management are discussed. Drug substituion, appropriate non-surgical and surgical treatment along with excellent plaque control lead to the regression and prevention of recurrence of drug-induced gingival overgrowth.

Pathological intracranial extradural hematoma in a 10-year-old child.

A nontraumatic spontaneous extradural hematoma, in a fully conscious 10-year-old male child, caused by a solitary eosinophilic granuloma of calvarium presented as a case of localized painful swelling of the head, which rapidly expanded and decreased in size. A plain CT-scan of the head with bone window revealed eroded right parietal bone with subperiosteal debris and extradural hematoma of mixed density. Immediate evacuation of the extradural clot and complete excision of the lesion was performed to prevent the deterioration of the patient and to achieve the histological diagnosis for further management.