A study of clinicopathological features and outcomes of crescentic glomerulonephritis

Background: Crescentic Glomerulonephritis (CrGN) is characterized by rapidly progressive renal failure. Most of the literatures have defined >50% crescents in biopsy as CrGN. Only very few studies have included the presence of <50% crescents as CrGN.Methods: To assess the clinico-pathological features and outcome of CrGN with >10% crescents on renal biopsy and comparing them splitting our diagnosis into Immune Complex Mediated CrGN (ICCGN) and non-immune complex mediated CrGN (NICCGN) groups.Results: ICCGN was the commonest group. When compared to ICCGN group, NICCGN patients were older, anuric, had more glomerular necrosis and severe IFTA in biopsy at presentation, more became dialysis dependent at index visit discharge. When patients with >50% crescents in both the groups were compared similar results were seen except that infective complications and proliferative lesions were more in ICCGN. When patients with <50% crescents in both the groups were compared similar findings were seen except that no difference was seen in clinical features and dialysis dependency between them.Conclusions: Oliguria at presentation, Hb <9 g/dl, index visit eGFR<15 ml/min, crescents >60%, moderate to severe IFTA are the independent risk factors for dialysis dependency at index visit discharge.

Blistering mucocutaneous disease of oral cavity Pemphigus vulgaris 8 year study in Nalgonda population

Background: Autoimmune disorders are conditions in which autoantibodies are directed against a single organ or tissue resulting in localized tissue damage. Pemphigus includes a group of autoimmune blistering diseases of skin and mucous membranes characterized by intra dermal blisters and immunologically by finding of circulating immunoglobulin G antibody directed against the cell surface of keratinocytes. Objectives: To analyze age distribution of Pemphigus vulgaris, prevalence among males and females, predominant oral site and clinical presentation. Materials and methods: A retrospective study of 31 cases of Pemphigus vulgaris obtained over a period of 8 years from January 2008 to September 2015 in the Department of Oral Pathology, Kamineni Institute of Dental Sciences was designed. Clinical details of age, sex, intraoral distribution and oral presentation were noted. P Pavan, T Madhusudan Rao, Pavan G Kulkarni, SRK Nandan, Shyam Prasad Reddy, M Keerthi. Blistering mucocutaneous disease of oral cavity Pemphigus vulgaris – 8 year study in Nalgonda population. IAIM, 2017; 4(1): 58-63. Page 59 Results: Age distribution of Pemphigus vulgaris was 30 – 70 years with a mean age of 49.12 years. Mean age of presentation in males was 45.5 years and in females 46.76 years. Females are more commonly affected than males with a ratio of 2:1. Most commonly affected sites were buccal mucosa, lips and palate, tongue, floor of mouth and skin. Erosions and encrustations were the most common clinical presentation. Conclusion: Pemphigus vulgaris is a fatal disease if left untreated. The skin and the mucosa are majorly involved and oral mucosa is often affected first. The study elucidates the characterization of Pemphigus vulgaris so that early diagnosis can be made. As oral lesions precede, oral health care professionals can play a major role in early diagnosis and managing oral lesions.

Preparation and Evaluation of Novel Expandable Drug Delivery System.

Aims: The purpose of this research is to develop a novel expandable gastroretentive dosage form (GRDF), based on unfolding mechanism. It consists of a drug loaded bilayer polymeric film, folded into a hard gelatin capsule. Gastric retention is achieved due to unfolding of the dosage form within 15-20 min. Furosemide is selected as the drug candidate for this work. Due to its narrow absorption window, Furosemide has to be administered to the upper parts of the intestine in order to maintain sustained therapeutic levels. This may be achieved by a GRDF. Methodology: Films were prepared by solvent-casting technique using Ethyl cellulose, HPMC E15 and Eudragit RLPO as polymers and dibutyl phthalate as the plasticizer in both layers. The film with zigzag folding in the capsule was shown to unfold in the gastric juice and provide drug release up to 12 h in the acidic medium. The films were evaluated for weight & thickness variation, mechanical properties, in vitro drug release and unfolding behavior based on the mechanical shape memory of polymers. Absence of drug polymer interaction and uniform drug dispersion in the polymeric layers was revealed by DSC, XRD studies and SEM. The GRDF location in the gastrointestinal tract was determined by X-ray studies. Results: X-ray studies revealed that the GRDF is retained in the stomach up to 6± 0.5 h in fasting condition and 8 h in fed state. Conclusion: The polymers used in the development of GRDFs were safe and proper combination of these polymers will yield a novel expandable GRDF with good in vitro drug release in acidic media, mechanical properties, and unfolding behaviour. These outcomes demonstrate that the GRDF may be used to improve furosemide therapy and can be applied to extend the absorption of other narrow absorption window drugs that require continuous input.

N-terminal PDZ-like domain of chromatin organizer SATB1 contributes towards its function as transcription regulator.

The special AT-rich DNA-binding protein 1 (SATB1) is a matrix attachment region (MAR)-binding protein that acts as a global repressor via recruitment of CtBP1:HDAC1-containing co-repressors to its binding targets. The N-terminal PSD95/Dlg-A/ZO-1 (PDZ)-like domain of SATB1 mediates interactions with several chromatin proteins. In the present study, we set out to address whether the PDZ-domain-mediated interactions of SATB1 are critical for its in vivo function as a global repressor. We reasoned that since the N-terminal PDZ-like domain (amino acid residues 1–204) lacks DNA binding activity, it would fail to recruit the interacting partners of SATB1 to its genomic binding sites and hence would not repress the SATB1-regulated genes. Indeed, in vivo MAR-linked luciferase reporter assay revealed that overexpression of the PDZ-like domain resulted in de-repression, indicating that the PDZ-like domain exerts a dominant negative effect on genes regulated by SATB1. Next, we developed a stable dominant negative model in human embryonic kidney (HEK) 293T cells that conditionally expressed the N-terminal 1–204 region harbouring the PDZ-like domain of SATB1. To monitor the effect of sequestration of the interaction partners on the global gene regulation by SATB1, transcripts from the induced and uninduced clones were subjected to gene expression profiling. Clustering of expression data revealed that 600 out of 19000 genes analysed were significantly upregulated upon overexpression of the PDZ-like domain. Induced genes were found to be involved in important signalling cascades and cellular functions. These studies clearly demonstrated the role of PDZ domain of SATB1 in global gene regulation presumably through its interaction with other cellular proteins.