Radioprotective and cytoprotective activity of Tinospora cordifolia stem enriched extract containing cordifolioside-A

Objectives:

The present study was undertaken to evaluate the radioprotective and cytoprotective potential of cordifolioside-A, a primary active constituent of n-butanol fraction of Tinospora Cordifolia (NBTC) against 4 Gy-γ radiation in mice and cyclophosphamide induced genotoxicity.

Materials and Methods:

Presence of cordifolioside-A in NBTC stem ethanolic extract was confirmed by high performance thin layer chromatography (HPTLC) analysis. Radioprotective activity was evaluated at 80 and 120 mg/kg, intraperitoneal (i.p.) dose of NBTC administered 15 days prior to whole body radiation exposure by observing survival rate, change in body weight, hematology, spleen colony forming unit (CFU), and micronucleus (MN) expression. Cytoprotective activity of NBTC was evaluated at 5, 10, and 15 mg/ml concentrations on Allium cepa root meristem growth against cyclophosphamide.

Results:

HPTLC analysis of standard cordifolioside A, and NBTC confirmed the presence of cordifolioside-A in NBTC with the retention factor value of 0.86. Administration of NBTC (120 mg/kg, i.p.) produced significant protection against radiation in terms of increased survival rate, body weight retention, hematological parameters, spleen CFU assay (P < 0.01), and decreased MN expression (P < 0.01). Cytoprotectivity was observed maximally at 10 mg/ml NBTC concentration with significant increase in root growth (P < 0.01), non-toxic mitotic index (MI) (65.9%) and lesser chromosomal aberrations (15.4%). NBTC at 10 mg/ml concentration showed very few C-anaphase compared to aberrations like fragmentation, C-anaphase, multipolarity and sticky chromosome in cyclophosphamide alone.

Conclusion:

The results suggest that enriched NBTC containing cordifolioside-A has a potential in vivo radioprotective effect as well as in vitro cytoprotective activity.KEY WORDS: Cordifolioside-A, cytoprotective activity, radioprotective activity, Tinospora cordifolia     

A Study of Manifestations of Extrapulmonary Tuberculosis in the ENT Region

Though tuberculosis (TB) primarily affects lungs, extra pulmonary tuberculosis (EPTB) is also common, especially in high disease load areas and mainly manifests in ENT region. To study the different manifestations of tuberculosis in ENT region in terms of presentation, disease process, treatment and outcome. Records of patients diagnosed and treated for TB in the ENT region at our institute’s DOTS centre for a two and half year period were analysed for presenting complaints, examination findings, diagnostic features, treatment modes and outcome. Out of 3750 cases diagnosed as TB, 230 had EPTB. 211 cases had ENT manifestations. Majority of the cases were male and in the fourth decade of life. Commonest manifestation was cervical lymphadenopathy with 201 cases. Fine needle aspiration cytology was mostly diagnostic and category I anti TB treatment (AKT) achieved cure. The six cases of TB otitis media presented with ear discharge, sometimes bloody and had varied tympanic membrane findings and facial palsy in two cases with different types and degrees of hearing loss. Diagnosis was confirmed by histology of tissue removed during surgery. Patients completed category I AKT. Hearing and facial palsy did not improve. There were three cases of TB laryngitis and one of nasal TB both of which were confirmed by tissue diagnosis and responded well to AKT. Most of the results in the present study conform to findings of other studies. High degree of suspicion is necessary to reach diagnosis. Category I AKT is effective. Some cases may require surgery.     

Arginine attenuates methylglyoxal- and high glucose-induced endothelial dysfunction and oxidative stress by an endothelial nitric-oxide synthase-independent mechanism

The mechanisms of ethanol addiction are not completely understood. The mesolimbic dopaminergic system is involved in many drug-related behaviors, including ethanol self-administration. The dopaminergic neurons in this system originate in the ventral tegmental area (VTA) and are under the control of GABAergic transmission. Our previous in vitro electrophysiological data indicate that glycine receptors (GlyRs) exist on the GABAergic terminals, which make synapses on VTA dopaminergic neurons, and activation of these GlyRs reduces GABAergic transmission and increases the activity of VTA dopaminergic neurons. In the current study, we tested the hypothesis that the activation of the presynaptic GlyRs in the VTA might interfere with ethanol self-administration. Glycine and strychnine, the selective antagonist of GlyRs, were injected, either alone or in combination, into the VTA of rats. Ethanol self-administration by rats was evaluated by using three different drinking models: intermittent access, continuous access, and operant self-administration. We found that the infusion of glycine into the VTA selectively reduced the intake of ethanol but not sucrose or water in rats chronically exposed to ethanol under the intermittent-access and continuous-access procedures and decreased lever-press responding for ethanol under an operant self-administration procedure. The effects of glycine probably were mediated by strychnine-sensitive GlyRs, because the coinjection of glycine and strychnine reduced neither ethanol intake in the home cages nor lever-press responding for ethanol in the operant chambers. Thus, GlyRs in the VTA may play a critical role in ethanol self-administration in animals chronically exposed to ethanol. Therefore, drugs targeting GlyRs may be beneficial for alcoholics.     

Gap junctional coupling with cardiomyocytes is necessary but not sufficient for cardiomyogenic differentiation of cocultured human mesenchymal stem cells

Gap junctional coupling is important for functional integration of transplanted cells with host myocardium. However, the role of gap junctions in cardiomyogenic differentiation of transplanted cells has not been directly investigated. The objective of this work is to study the role of connexin43 (Cx43) in cardiomyogenic differentiation of human mesenchymal stem cells (hMSCs). Knockdown of Cx43 gene expression (Cx43↓) was established in naturally Cx43-rich fetal amniotic membrane (AM) hMSCs, while Cx43 was overexpressed (Cx43↑) in inherently Cx43-poor adult adipose tissue (AT) hMSCs. The hMSCs were exposed to cardiomyogenic stimuli by coincubation with neonatal rat ventricular cardiomyocytes (nrCMCs) for 10 days. Differentiation was assessed by immunostaining and whole-cell current clamping. To establish whether the effects of Cx43 knockdown could be rescued, Cx45 was overexpressed in Cx43↓ fetal AM hMSCs. Ten days after coincubation, not a single Cx43↓ fetal AM hMSC, control adult AT MSC, or Cx43↑ adult AT mesenchymal stem cell (MSC) expressed α-actinin, while control fetal AM hMSCs did (2.2% ± 0.4%, n = 5,000). Moreover, functional cardiomyogenic differentiation, based on action potential recordings, occurred only in control fetal AM hMSCs. Of interest, Cx45 overexpression in Cx43↓ fetal AM hMSCs restored their ability to undergo cardiomyogenesis (1.6% ± 0.4%, n = 2,500) in coculture with nrCMCs. Gap junctional coupling is required for differentiation of fetal AM hMSCs into functional CMCs after coincubation with nrCMCs. Heterocellular gap junctional coupling thus plays an important role in the transfer of cardiomyogenic signals from nrCMCs to fetal hMSCs but is not sufficient to induce cardiomyogenic differentiation in adult AT hMSCs.     

SGLT1 inhibition boon or bane for diabetes-associated cardiomyopathy

Chronic hyperglycaemia is a peculiar feature of diabetes mellitus (DM). Sequential metabolic abnormalities accompanying glucotoxicity are some of its implications. Glucotoxicity most likely corresponds to the vascular intricacy and metabolic alterations, such as increased oxidation of free fatty acids and reduced glucose oxidation. More than half of those with diabetes also develop cardiac abnormalities due to unknown causes, posing a major threat to the currently available marketed preparations which are being used for treating these cardiac complications. Even though impairment in cardiac functioning is the principal cause of death in individuals with type 2 diabetes (T2D), reducing plasma glucose levels has little effect on cardiovascular disease (CVD) risk. In vitro and in vivo studies have demonstrated that inhibitors of sodium glucose transporter (SGLT) represent a putative therapeutic intervention for these pathological conditions. Several clinical trials have reported the efficacy of SGLT inhibitors as a novel and potent antidiabetic agent which along with its antihyperglycaemic activity possesses the potential of effectively treating its associated cardiac abnormalities. Thus, hereby, the present review highlights the role of SGLT inhibitors as a successful drug candidate for correcting the shifts in deregulation of cardiac energy substrate metabolism together with its role in treating diabetes-related cardiac perturbations.     

Neutrophilic Panniculitis in a child with MYSM1 deficiency

Neutrophilic panniculitis (NP) with myelodysplasia has been described in adults but not in children. We report a case of NP associated with myelodysplasia in a child with MYSM1 deficiency, a newly described syndrome with primary immunodeficiency (PI), bone marrow failure, and developmental aberrations.