Risk of hepatitis with various reintroduction regimens of anti-tubercular therapy: a systematic review and network meta-analysis

ABSTRACT

Objective: To compare risk of hepatotoxicity between various regimens for reintroduction of antitubercular therapy (ATT) in patients with previous episode of ATT hepatitis.

Methods: We searched various databases (PubMed, Embase, CENTRAL, Scopus, WoS and LILACS) for studies comparing ATT reintroduction regimens using terms ‘drug-induced liver injury’ and ‘antitubercular drugs’ AND ‘reintroduction’. The reintroduction regimens i.e concomitant (all drugs introduced together), sequential (reintroduction of one drug in full dose followed by another) or incremental (one drug in a low dose and then higher dose followed by next drug) were compared using Bayesian approach for network meta-analysis with random-effect model. Cochrane revised tool was used to assess risk of bias in included studies (RoB 2.0).

Results: Four randomized studies with 577 patients were eligible for analysis. Compared with concomitant regimen (baseline comparator), incremental regimen appeared to have lower risk of ATT hepatitis (odds ratio [OR] 0.24; 95% CrI 0.017, 1.2) as also the sequential regimen (OR 0.33; 95% CrI 0.033, 1.7). Rifampicin first and isoniazid first reintroduction regimens were similar via-a-vis recurrence of hepatotoxicity.

Conclusion: The sequential and incremental regimen may be better than concomitant regimen in reducing risk of ATT hepatitis although the odds did not achieve statistical significance.     

Comparative study of anatomical specimens using plastination by araldite HY103, polypropylene resin, 6170H19 Orthocryl and silicone – A qualitative study

Background

Most of the organs and tissues are preserved in formalin with its own set of disadvantages. Plastination is a unique method of permanently preserving tissue in a life like state. Plastination developed by western authorities is a labour and equipment intensive affair. Most common polymer used is S10, however this study uses easily available alternative polymers for plastination.

Method

Various polymers like Epoxy resins, Polypropylene resins, Orthocryl and silicone were used in plastinating the anatomical specimens. Specific methods were used for solid, hollow organs and brain specimens. The specimens were made to undergo stages of fixation, dehydration, impregnation and curing. The results were studied and interpreted under various parameters.

Results

The results were interpreted under various parameters like shrinkage, retention of colour, odour, pliability and retention of gross anatomy. The study concluded that Orthocryl and Epoxy resins retained maximum colour with minimal shrinkage while maximum discolouration was with polypropylene plastinates. Brain sections were best preserved in Orthocryl.

Conclusion

The study concluded that indigenous methods and materials can produce quality plastinates which can be an important adjunct to traditional methods of teaching however more studies need to be done for refinement.     

Surveillance of Artemisinin Resistance in Plasmodium falciparum in India Using the kelch13 Molecular Marker

Malaria treatment in Southeast Asia is threatened with the emergence of artemisinin-resistant Plasmodium falciparum. Genome association studies have strongly linked a locus on P. falciparum chromosome 13 to artemisinin resistance, and recently, mutations in the kelch13 propeller region (Pfk-13) were strongly linked to resistance. To date, this information has not been shown in Indian samples. Pfk-13 mutations were assessed in samples from efficacy studies of artemisinin combination treatments in India. Samples were PCR amplified and sequenced from codon 427 to 727. Out of 384 samples, nonsynonymous mutations in the propeller region were found in four patients from the northeastern states, but their presence did not correlate with ACT treatment failures. This is the first report of Pfk-13 point mutations from India. Further phenotyping and genotyping studies are required to assess the status of artemisinin resistance in this region.     

Design,Synthesis, Biological Screening,and Molecular Docking Studies of Piperazine-Derived Constrained Inhibitors of DPP-IV for the Treatment of Type 2 Diabetes

Novel piperazine-derived conformationally constrained compounds were designed, synthesized, and evaluated for in vitro Dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. From a library of compounds synthesized, 1-(2-(4-(7-Chloro-4-quinolyl)piperazin-1-yl)acetyl)pyrrolidine ( 2g ) was identified as a potential DPP-IV inhibitor exhibiting better inhibitory activity than P32/98, reference inhibitor. The in vivo studies carried out in STZ and db/db mice models indicated that the compound 2g showed moderate antihyperglycemic activity as compared to the marketed drug Sitagliptin. A two-week repeated dose study in db/db mice revealed that compound 2g significantly declined blood glucose levels with no evidence of hypoglycemia risk. Furthermore, it showed improvement in insulin resistance reversal and antidyslipidemic properties. Molecular docking studies established good binding affinity of compound 2g at the DPP-IV active site and are in favor of the observed biological data. These data collectively suggest that compound 2g is a good lead molecule for further optimization studies.     

Epibulbar schwannoma in a 12-year-old boy: A case report and review of literature

Schwannomas are benign, encapsulated, primary neurilemmal tumors composed of proliferating Schwann cells. Schwannomas are commonly seen in the orbit, but are rare on the epibulbar surface. Herein, we report a case of a 12-year-old boy who presented to us with a slow-growing painless subconjunctival mass in the left eye. There was no intraocular extension of the mass and intra-operatively, the mass could be clearly delineated and was excised off the underlying sclera. Histopathological examination of the mass showed typical features of schwannoma and immunohistochemistry helped to confirm the diagnosis. There was no recurrence of the lesion observed at follow-up 26 months after surgery. Here, we describe this uncommon tumor and review the available literature. Although rare, an epibulbar schwannoma should be considered in the differential diagnosis of an amelanotic, painless subconjunctival nodular mass. Excision of the lesion is the recommended treatment.     

Fatty acid synthase is a metabolic oncogene targetable in malignant peripheral nerve sheath tumors

BackgroundMalignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas with minimal therapeutic opportunities. We observed that lipid droplets (LDs) accumulate in human MPNST cell lines and in primary human tumor samples. The goal of this study was to investigate the relevance of lipid metabolism to MPNST survival and as a possible therapeutic target.MethodsBased on preliminary findings that MPNSTs accumulate LDs, we hypothesized that a deregulated lipid metabolism supports MPNST cell survival/proliferation rate. To test this, we examined respiration, role of fatty acid oxidation (FAO), and the enzyme fatty acid synthase involved in de novo fatty acid synthesis in MPNSTs using both genetic and pharmacological tools.ResultsWe demonstrate that LDs accumulate in MPNST cell lines, primary human and mouse MPNST tumors, and neural crest cells. LDs from MPNST cells disappear on lipid deprivation, indicating that LDs can be oxidized as a source of energy. Inhibition of FAO decreased oxygen consumption and reduced MPNST survival, indicating that MPNST cells likely metabolize LDs through active FAO. FAO inhibition reduced oxygen consumption and survival even in the absence of exogenous lipids, indicating that lipids synthesized de novo can also be oxidized. Consequently, inhibition of de novo fatty acid synthesis, which is overexpressed in human MPNST cell lines, effectively reduced MPNST survival and delayed induction of tumor growth in vivo.ConclusionOur results show that MPNSTs depend on lipid metabolic pathways and suggest that disrupting lipid metabolism could be a potential new strategy for the development of MPNST therapeutics.     

Sentinel Lymph Node Localization Using 1 % Isosulfan Blue Dye in Cases of Early Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

To study the use of 1 % isosulfan blue dye in identifying sentinel node, sensitivity and specificity of frozen section and predictive value of sentinel node in predicting other nodal status in the cases of oral cavity and oropharyngeal squamous cell carcinoma. 15 patients of oral cavity and oropharyngeal SCC with clinically N0 neck, who required WLE of the primary lesion as well as neck dissection as per recommended treatment protocol, were selected from OPD. 1 % Isosulfan dye was injected peritumorally intraoperatively after the induction of general anaesthesia. Neck dissection was performed and first node taking up the blue dye was identified, dissected, removed and was sent for frozen section. In two of the 15 cases a sentinel node was identified (sensitivity of the technique—13 %). Both the sentinel nodes were positive for presence of metastasis on final histopathology (specificity—100 %). However, five cases had nodal metastasis on final histopathological examination of the neck dissection specimen (sensitivity of sentinel lymph node biopsy—40 %). Frozen section examination had a sensitivity and specificity of 100 %. All data was analyzed using SPSS 16 software. Use of 1 % Isosulfan Dye for identification of sentinel node is a simple and cheap technique, however, it has low sensitivity as compared to the use of triple diagnostic procedure consisting of lymphoscintigraphy, per op gamma probe localization and using isosulfan dye for sentinel node identification. Sentinel lymph node is representative of nodal status and correlates well with the final histopathological examination of the dissected neck nodes.     

To Assess the Efficacy of Modality Slow Motion Dynamic Video Endoscopy of Eustachian Tube in Chronic Middle Ear Pathologies

Eustachian tube dysfunction (ETD) has a role in chronic otitis media (COM) is a well known fact and number of modalities have come up for its assessment—slow motion dynamic videoendoscopy (SMDV) being the latest. (i) To find prevalence of ETD in COM and (ii) to check the efficacy of SMDV in detecting dysfunction as compared to gold standard tympaometry (TYM). It’s a prospective analytical study with total of 100 patients of chronic otitis media, hence 200 ears were tested for ETD by TYM and SMDV. Prevalence of ETD was noted as 35.5 % in COM whereas the two testing modalities TYM versus SMDV showed agreement in 161 cases out of the 200 ears giving a moderate agreement of statistical significance (Kappa test) suggesting SMDV to be included in standard of protocol when assessing ETD along with TYM.     

Antimicrobial properties of black grape (Vitis vinifera L.) peel extracts against antibiotic-resistant pathogenic bacteria and toxin producing molds

Aim:

Black grape peel possesses a substantial amount of polyphenolic antimicrobial compounds that can be used for controlling the growth of pathogenic microorganisms. The purpose of this study was to assess antibacterial and antifungal activity of black grape peel extracts against antibiotic-resistant pathogenic bacteria and toxin producing molds, respectively.

Materials and Methods:

Peel of grape was subjected to polyphenolic extraction using different solvents viz., water, ethanol, acetone, and methanol. Antibiotic-resistant strains of Staphylococcus aureus, Enterococcus faecalis, Enterobacter aerogenes, Salmonella typhimurium, and Escherichia coli were screened for the antibacterial activity of different grape extracts. Antibacterial activity was analyzed using agar well diffusion method. Penicillium chrysogenum, Penicillium expansum, Aspergillus niger and Aspergillus versicolor were screened for the antifungal activity. Antifungal activity was determined by counting nongerminated spores in the presence of peel extracts.

Results:

As compared to other solvent extracts, methanol extracts possessed high antibacterial and antifungal activity. S. typhimurium and E. coli showed complete resistance against antibacterial action at screened concentrations of grape peel extracts. Maximum zone of inhibition was found in case of S. aureus, i.e., 22 mm followed by E. faecalis and E. aerogenes, i.e., 18 and 21 mm, respectively, at 1080 mg tannic acid equivalent (TAE)/ml. The maximum and minimum percent of growth inhibition was shown by P. expansum and A. niger as 73% and 15% at 1080 TAE/ml concentration of grape peel extract, respectively.

Conclusions:

Except S. typhimurium and E. coli, growth of all bacterial and mold species were found to be significantly (P < 0.05) inhibited by all the solvent extracts.KEY WORDS: Antibacterial activity, antifungal activity, polyphenolic compounds, Vitis vinifera L, zone of inhibition