Development and evaluation of osmotically controlled oral drug delivery system of glipizide.

Extended release formulation of glipizide based on osmotic technology was developed and evaluated. The effect of different formulation variables, namely, level of solubility modifier in the core, membrane weight gain, and level of pore former in the membrane, were studied. Drug release was found to be affected by the level of solubility modifier in the core formulation. Glipizide release was inversely proportional to the membrane weight but directly related to the initial level of pore former (PVP) in the membrane. Burst strength of the exhausted shells increased with the weight gain of the membrane. On the other hand, burst strength decreased with an increase in the level of pore former in the membrane. Drug release from the developed formulations was independent of pH and agitational intensity, but dependent on the osmotic pressure of the release media. Results of SEM studies showed the formation of pores in the membrane from where the drug release occurred. The numbers of pores were directly proportional to the initial level of pore former in the membrane. The manufacturing procedure was found to be reproducible and formulations were stable after 3 months of accelerated stability studies.     

The role of renal nerve stimulation in percutaneous renal denervation for hypertension: A mini‐review

Recent trials have demonstrated the efficacy and safety of percutaneous renal sympathetic denervation (RDN) for blood pressure (BP)‐lowering in patients with uncontrolled hypertension. Nevertheless, major challenges exist, such as the wide variation of BP‐lowering responses following RDN (from strong response to no response) and lack of feasible and reproducible peri‐procedural predictors for patient response. Both animal and human studies have demonstrated different patterns of BP responses following renal nerve stimulation (RNS), possibly related to varied regional proportions of sympathetic and parasympathetic nerve tissues along the renal arteries. Animal studies of RNS have shown that rapid electrical stimulation of the renal arteries caused renal artery vasoconstriction and increased norepinephrine secretion with a concomitant increase in BP, and the responses were attenuated after RDN. Moreover, selective RDN at sites with strong RNS‐induced BP increases led to a more efficient BP‐lowering effect. In human, when RNS was performed before and after RDN, blunted changes in RNS‐induced BP responses were noted after RDN. The systolic BP response induced by RNS before RDN and blunted systolic BP response to RNS after RDN, at the site with maximal RNS‐induced systolic BP response before RDN, both correlated with the 24‐h ambulatory BP reductions 3–12 months following RDN. In summary, RNS‐induced BP changes, before and after RDN, could be used to assess the immediate effect of RDN and predict BP reductions months following RDN. More comprehensive, large‐scale and long term trials are needed to verify these findings.     

Connectomic assessment of injury burden and longitudinal structural network alterations in moderate‐to‐severe traumatic brain injury

Traumatic brain injury (TBI) is a major public health problem. Caused by external mechanical forces, a major characteristic of TBI is the shearing of axons across the white matter, which causes structural connectivity disruptions between brain regions. This diffuse injury leads to cognitive deficits, frequently requiring rehabilitation. Heterogeneity is another characteristic of TBI as severity and cognitive sequelae of the disease have a wide variation across patients, posing a big challenge for treatment. Thus, measures assessing network‐wide structural connectivity disruptions in TBI are necessary to quantify injury burden of individuals, which would help in achieving personalized treatment, patient monitoring, and rehabilitation planning. Despite TBI being a disconnectivity syndrome, connectomic assessment of structural disconnectivity has been relatively limited. In this study, we propose a novel connectomic measure that we call network normality score (NNS) to capture the integrity of structural connectivity in TBI patients by leveraging two major characteristics of the disease: diffuseness of axonal injury and heterogeneity of the disease. Over a longitudinal cohort of moderate‐to‐severe TBI patients, we demonstrate that structural network topology of patients is more heterogeneous and significantly different than that of healthy controls at 3 months postinjury, where dissimilarity further increases up to 12 months. We also show that NNS captures injury burden as quantified by posttraumatic amnesia and that alterations in the structural brain network is not related to cognitive recovery. Finally, we compare NNS to major graph theory measures used in TBI literature and demonstrate the superiority of NNS in characterizing the disease.     

In vitro antiprotozoal activity of some xanthones isolated from the roots of Andrographis paniculata

Four xanthones isolated from the roots of Andrographis paniculata were tested in vitro for antiprotozoal activity against Trypanosoma brucei brucei, Trypanosoma cruzi and Leishmania infantum. Compound TDR13011 (1,2-dihydroxy-6,8-dimethoxy-xanthone) showed good activity against T. b. brucei and L. infantum with a 50% inhibitory concentration (IC50) of 4.6 microg/ml and 8 microg/ml respectively. Xanthones from the roots of Andrographis paniculata exhibited promising anti-protozoal activity and these compounds could be chemically modified to obtain a more potent product.     

Targeting inflammation in lower-risk MDS

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Molecular and Immunological Characterization of Heat Shock Protein 70 (HSP70) Gene from Buffalo

Heat shock protein 70 (HSP70) is a predominant member of the HSP family of proteins, which play a variety of functions in the cells and are responsible for cytoprotection under stress conditions. The present study was characterized by HSP70 (orf) in buffalo (Buablus bubalis). Genomic DNA was isolated from lymphocytes and that was used for PCR amplification of HSP70 gene. Polymerase chain reaction product (1,926 bp) was cloned in pGEM-T easy vector and sequenced. Sequence analysis revealed 1,926 bp long open reading frame of HSP70 gene encoding 641 amino acids in buffalo. The amino acid sequence showed 98 % identity with Bos taurus, Bos indicus, Yak, Capra hircus and 90–95 % identity with Camelus dromedaries, Felis catus, Canis familiaris, Sus scrofa, and Homo sapiens. The expression of this gene was in prokaryotic expression vector pPRoExHTa producing a recombinant protein of ~70 kDa, which is detected by SDS-PAGE. The tagged protein purified by Ni-NTA affinity chromatography under denaturing conditions was confirmed by western blotting using Ni-NTA HRP conjugate and 4 chloro-1-naphthol as substrate. Recombinant HSP70 was injected in mice and antiserum contained polyclonal antibody, which was detected by western blot. The recombinant HSP70 protein obtained may be used for the development of an assay for detection of thermal stress.     

Clinical profile,multimodal imaging,and treatment response in macular serpiginous choroiditis

Purpose:To describe the clinical profile, multimodal imaging, and treatment response in macular serpiginous choroiditis (MSC).Methods:Clinical records of 16 eyes (14 patients) with MSC presenting to a tertiary eye care institute between 2015 and 2019 were analyzed retrospectively.Results:Mean age of 14 patients presenting with MSC was 33 ± 13 yrs with 64% males and 36% females. Mean visual acuity of the eyes with MSC at presentation was 0.43 ± 0.46 (logMAR) improving to 0.16 ± 0.28 (logMAR) at final visit. Thirteen eyes (81.3%) had active lesion at presentation. Mantoux test was positive in seven patients (50%) and QuantiFERON TB gold test positive in 10 patients (71%). HRCT chest showed latent tuberculosis in seven patients (50%). All patients underwent multimodal imaging. All patients received oral steroids as treatment therapy; 11 patients also received immunosuppressives, nine patients received additional anti-tubercular therapy (ATT). Mean duration of follow-up for the patients was 18 ± 10 months. A total of eight (50%) eyes had recurrence of lesions after an average duration of 14 ± 14 (3-36) months and were restarted on the treatment as per the requirement. At final follow-up, all eyes showed a good response to treatment and had healed lesions. Comparing the final BCVA to the initial BCVA, 38% (n = 6) showed improvement, 56% (n = 9) remained stable, and 6% (n = 1) eyes worsened at the final follow-up.Conclusion:Clinical profile and presentation of MSC is similar to that of CSC, and combination treatment with intravenous methyl prednisolone (IVMP), steroids, immunosuppressives, and ATT can salvage vision. A high suspicion of associated tuberculosis in endemic regions should be kept in mind.