Antidiabetic activity of aqueous root extract of Merremia tridentata (L.) Hall. f. in streptozotocin-induced-diabetic rats

ObjectiveTo investigate the antidiabetic effect of aqueous extract of Merremia tridentata (M. tridentata) root (MTRAE) in normal, glucose-loaded hyperglycemic and streptozotocin (STZ)-induced diabetic rats.MethodsOral administration of MTRAE at the doses of 50, 100 and 150 mg/kg was studied in normal, glucose-loaded and STZ-diabetic rats. The three doses caused significant reduction in blood glucose levels in all the models.ResultsThe effect was more pronounced in 100 and 150 mg/kg than 50 mg/kg. MTRAE also showed significant increase in serum insulin, body weight and glycogen content in liver and skeletal muscle of STZ-induced diabetic rats while there was significant reduction in the levels of serum triglyceride and total cholesterol. MTRAE also showed significant antilipidperoxidative effect in the pancreas of STZ-induced diabetic rats. The antidiabetic effect of M. tridentata was compared with glibenclamide, a well known hypoglycemic drug.ConclusionsThe results indicate that aqueous extract of M. tridentata root possesses significant antidiabetic activity.     

Expanded natural killer cells augment the antimyeloma effect of daratumumab,bortezomib, and dexamethasone in a mouse model

The use of natural killer (NK) cells is a promising and safe immunotherapeutic approach in the field of cancer immunotherapy. However, combination treatments are required to enhance the effector functions and therapeutic efficacy of NK cells. In this study, we investigated the potential of daratumumab (Dara), bortezomib, and dexamethasone (Dvd) to augment the antitumor effects of NK cells in a multiple myeloma (MM) xenograft mouse model. NK cells were expanded and activated using the K562-OX40 ligand and membrane-bound IL-18 and IL-21 in the presence of IL-2 and IL-15 from peripheral blood mononuclear cells from MM patients. A human MM xenograft model was established using human RPMI8226-RFP-FLuc cells in NOD/SCID IL-2Rγ^null (NSG) mice. Tumor-bearing mice were divided into six treatment groups: no treatment, expanded NK cells (eNKs), Dara, Dara + eNKs, Dvd, and Dvd + eNKs. Dvd treatment strongly enhanced the cytotoxicity of eNKs by upregulating expression of NK cell activation ligands, downregulating expression of NK cell inhibitory ligands, and promoting antibody-dependent cellular cytotoxicity. The combination of eNKs with Dvd significantly prolonged mouse survival and reduced the tumor burden and serum M-protein level. Furthermore, Dvd pretreatment significantly increased eNK persistence and homing to MM sites. Our findings suggest that Dvd treatment potentiates the antimyeloma effects of NK cells expanded and activated ex vivo by modulating immune responses in MM-bearing mice.     

Free radical scavenging property and antiproliferative activity of Rhodiola imbricata Edgew extracts in HT-29 human colon cancer cells

ObjectiveTo investigate the in vitro antioxidant and antiproliferative activity of rhizome extracts of Rhodiola imbricata (R. imbricata) in HT-29 human colon cancer cell line.MethodsThe successively extracted rhizome of R. imbricata using various solvents was analyzed for their total phenolics, tannins and flavonoid contents. In vitro antioxidant activity was evaluated by employing different assays, including DPPH, ABTS radical scavenging assays, FRAP, phosphomolybdenum reduction assay, superoxide anion, hydroxyl radical scavenging activities and metal chelating ability.ResultsAcetone and methanol extracts recorded higher phenolic content and showed comparable antioxidant activity with standard reference. Additionally, they also inhibited the proliferation of HT-29 cells upon treatment at higher concentration (200 μg/mL) (acetone and methanol, 84% and 84%, respectively). On examination acetone extract exhibited antiproliferative activity in a concentration dependent manner whereas, methanol extract showed both dose dependent and time dependent inhibitory activity.ConclusionsThe results obtained justify the traditional usage of R. imbricata from their promising antioxidant activity.     

Antidepressant-like effect of novel 5-HT3 receptor antagonist N-n-butyl-3-ethoxyquinoxalin-2-carboxamide (6p): An approach using rodent behavioral antidepressant tests

Objective:

The present study was designed to investigate the antidepressant potential of N-n-butyl-3-ethoxyquinoxalin-2-carboxamide (6p), a novel 5-HT₃ receptor antagonist in rodent behavioral models of depression.

Materials and Methods:

The compound 6p was examined in various behavioral models like forced swim test (FST), tail suspension test (TST), mechanistic models [5-hydroxytryptophan (5-HTP)-induced head twitch and reserpine-induced hypothermia (RIH)], and in chronic surgery model-olfactory bulbectomy in rats.

Results:

Compound 6p (1, 2, and 4 mg/kg, i.p.) exhibited antidepressant-like effect in FST and TST after acute treatment without having an effect on baseline locomotor activity. Moreover, 6p (2 mg/kg, i.p.), potentiated the 5-HTP–induced head twitch responses in mice and inhibited the RIH in rats. Chronic treatment (14 days) with 6p (1 and 2 mg/kg, p.o.) and paroxetine (10 mg/kg, p.o.) in rats significantly reversed the behavioral anomalies induced by bilateral olfactory bulbectomy using open field exploration.

Conclusion:

The preliminary studies reveal that compound 6p exhibits antidepressant-like effect in behavioral rodent models of depression.KEY WORDS: 5-HT₃ receptor antagonists, antidepressant, forced swim test, quinoxaline, serotonin     

Ethnobotanical study of Kani tribes in Thoduhills of Kerala,South India

Ethnopharmacological relevance

India is having a rich vegetation with a wide variety of plants, because of the extreme variations in geographical and climatic conditions prevailing in the country. Plants have been used since ancient times for the treatment of various ailments. Especially, Kani tribal communities in Thodu hills of Kerala meet their healthcare needs by using non-timber minor forest products and preparations based on traditional knowledge. They still depend on medicinal plants and most of them have a basic knowledge of medicinal plants which are used for first aid remedies, to treat cough, cold, fever, headache, poisonous bites and some simple ailments. The present study was initiated with an aim to identify traditional healers who are practicing herbal medicine among the Kani tribals in Thodu hills of Kerala, India and quantitatively document their indigenous knowledge on the utilization of medicinal plants, particularly most common ethnomedicinal plants.

Methods

A field study was carried out over a period of 1 year in Thodu hills. The ethnomedicinal information was collected through interviews among the Kani traditional healers. The collected data were analyzed through use value (UV), informant consensus factor (Fic), fidelity level (FL) and relative importance (RI).

Results

During the present study a total of 35 medicinal plant species belonging to 28 families and 34 genera have been documented. These plants were used to treat various diseases and ailments grouped under 14 disease categories, with the highest number of species (7) being used for liver problems, circulatory system and dermatological disorders, followed by skeleto muscular system disorders (6), and fever (5). In the study area the informant consensus about usages of medicinal plants ranges from 0.70 to 1 with an average value of 0.83. Herbs (46%) were the primary source of medicine, followed by shrubs (23%). Plumbago zeylanica (UV of 1.86) and Ocimum tenuiflorum (UV of 1.57) are the most frequently and popularly used medicinal plant species in the study area. Aristolochia tagala is rare and a vulnerable climber, Curculigo orchioides, Elephantopus scaber, Helicteres isora, Smilax zeylanica and Strychnos nux-vomica are rare species which need to be conserved for future use.

Conclusion

The high degree of consensus among the informants suggests that the current use and knowledge is still strong. The efficacy and safety of all the reported ethnomedicinal plants needs to be evaluated for phytochemical and pharmacological studies, especially the plants with high informant consensus factor, use value and fidelity level should be given priority to carry out bioassay and toxicity studies. We recommend the plants Plumbago zeylanica, Ocimum tenuiflorum, Artocarpus hirsutus, Andropogon muricatus, Helicteres isora, Coscinium fenestratum and Justicia adhatoda with high UV and RI values. Biophytum sensitivum, Curculigo orchioides, Strychnos nux-vomica, Gossypium hirsutum, Artocarpus heterophyllus, Elephantopus scaber, Pergularia daemia and Pyrrosia heterophylla (newly reported claims with highest FL) for further ethnopharmacological studies for the discovery of potential new drugs.     

High prevalence of Arginine to Glutamine Substitution at 98, 141 and 162 positions in Troponin I (TNNI3) associated with hypertrophic cardiomyopathy among Indians

ABSTRACT: BACKGROUND: Troponin I (TNNI3) is the inhibitory subunit of the thin filament regulatory complex Troponin, which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. Mutations (2-7%) in this gene had been reported in HCM. However, the frequencies of mutations and associated clinical presentation have not been established in cardiomyopathy patients of Indian origin, hence we have undertaken this study. METHODS: We have sequenced all the exons, including the exon-intron boundaries of TNNI3 gene in 101 hypertrophic cardiomyopathy patients (HCM), along with 160 healthy controls, inhabited in the same geographical region of southern India. RESULTS: Our study revealed a total of 16 mutations. Interestingly, we have observed Arginine to Glutamine (R to Q) mutation at 3 positions 98, 141 and 162, exclusively in HCM patients with family history of sudden cardiac death. The novel R98Q was observed in a severe hypertrophic obstructive cardiomyopathy patient (HOCM). The R141Q mutation was observed in two familial cases of severe asymmetric septal hypertrophy (ASH++). The R162Q mutation was observed in a ASH++ patient with mean septal thickness of 29 mm, and have also consists of allelic heterogeneity by means of having one more synonymous (E179E) mutation at g.4797: G [RIGHTWARDS ARROW] A: in the same exon 7, which replaces the very frequent codon (GAG: 85%) with rare codon (GAA: 14%). Screening for R162Q mutation in all the available family members revealed its presence in 9 individuals, including 7 with allelic heterogeneity (R162Q and E179E) of which 4 were severely affected. We also found 2 novel SNPs, (g.2653; G [RIGHTWARDS ARROW] A and g.4003 C [RIGHTWARDS ARROW] T) exclusively in HCM, and in silico analysis of these SNPs have predicted to cause defect in recognition/binding sites for proteins responsible for proper splicing. CONCLUSION: Our study has provided valuable information regarding the prevalence of TNNI3 mutations in Indian HCM patients and its risk assessment, these will help in genetic counseling and to adopt appropriate treatment strategies.     

Multiple Synchronous Verrucous Carcinomas of the Scalp in the Background of Generalized Verruca Vulgaris

Verrucous carcinoma (VC) is a clinicopathologic entity which is defined as a locally aggressive, clinically exophytic, slow-growing, well-differentiated, squamous cell carcinoma with negligible metastatic potential. The cutaneous form of VC is typically known to arise from the palmoplantar and the genitocrural areas. Involvement of the scalp is extremely rare. Multiple synchronous involvement of the scalp by VC along with associated generalized verruca vulgaris has possibly never been reported before. We present this unique report of VC in a 38-year-old male patient with emphasis on its atypical clinical presentation and the resultant challenges in management. Interestingly, the tumor cells of our patient were confirmed to be positive for human papillomavirus infection by polymerase chain reaction and by p16 immunohistochemistry.     

Giant cell tumour of the sacrum: a suggested algorithm for treatment

To investigate the outcome of our management of patients with giant cell tumour of the sacrum and draw lessons from this. A retrospective review of medical records and scans for all patients treated at our unit over the past 20 years with a giant cell tumour of the sacrum. Of the 517 patients treated at our unit for giant cell tumour over the past 20 years, only 9 (1.7%) had a giant cell tumour in the sacrum. Six were female, three male with a mean age of 34 (range 15–52). All, but two tumours involved the entire sacrum and there was only one purely distal to S3. The mean size was 10 cm and the most common symptom was back or buttock pain. Five had abnormal neurology at diagnosis, but only one presented with cauda equina syndrome. The first four patients were treated by curettage alone, but two patients had intraoperative cardiac arrests and although both survived all subsequent curettages were preceded by embolisation of the feeding vessels. Of the seven patients who had curettage, three developed local recurrence, but all were controlled with a combination of further embolisation, surgery or radiotherapy. One patient elected for treatment with radiotherapy and another had excision of the tumour distal to S3. All the patients are alive and only two patients have worse neurology than at presentation, one being impotent and one with stress incontinence. Three patients required spinopelvic fusion for sacral collapse. All patients are mobile and active at a follow-up between 2 and 21 years. Giant cell tumour of the sacrum can be controlled with conservative surgery rather than subtotal sacrectomy. The excision of small distal tumours is the preferred option, but for larger and more extensive tumours conservative management may well avoid morbidity whilst still controlling the tumour. Embolisation and curettage are the preferred first option with radiotherapy as a possible adjunct. Spinopelvic fusion may be needed when the sacrum collapses.     

GGN repeat length and GGN/CAG haplotype variations in the androgen receptor gene and prostate cancer risk in south Indian men

The ethnic variation in the GGN and CAG microsatellites of the androgen receptor (AR) gene suggests their role in the substantial racial difference in prostate cancer risk. Hence, we performed a case-control study to assess whether GGN repeats independently or in combination with CAG repeats were associated with prostate cancer risk in South Indian men. The repeat lengths of the AR gene determined by Gene scan analysis, revealed that men with GGN repeats ≤21 had no significant risk compared to those with >21 repeats (OR 0.91 at 95% CI-0.52–1.58). However, when CAG repeats of our earlier study was combined with the GGN repeat data, the cases exhibited significantly higher frequency of the haplotypes CAG ≤19/GGN ≤21 (OR-5.2 at 95% CI-2.17–12.48, P < 0.001) and CAG ≤19/GGN > 21(OR-6.9 at 95%CI-2.85–17.01, P < 0.001) compared to the controls. No significant association was observed between GGN repeats and prostate-specific antigen levels and the age at diagnosis. Although a trend of short GGN repeats length in high-grade was observed, it was not significant (P = 0.09). Overall, our data reveals that specific GGN/CAG haplotypes (CAG ≤19/GGN ≤21 and CAG ≤19/GGN > 21) of AR gene increase the risk of prostate cancer and thus could serve as susceptibility marker for prostate cancer in South Indian men.     

Population-based case-control study of DRD2 gene polymorphisms and alcoholism

Several independent lines of evidence for genetic contributions to vulnerability to alcoholism exist. Dopamine is thought to play a major role in the mechanism of reward and reinforcement in response to alcohol. D2 dopamine receptor (DRD2) gene has been among the stronger candidate genes implicated in alcoholism. In this study, alcohol use was assessed in 196 randomly selected Kota individuals of Nilgiri Hills, South India. Six DRD2 SNPs were assessed in 81 individuals with alcoholism and 151 controls to evaluate the association between single nucleotide polymorphisms (SNPs) and alcoholism. Of the three models (dominant, recessive, and additive) tested for association between alcoholism and DRD2 SNPs, only the additive model shows association for three loci (rs1116313, TaqID, and rs2734835). Of six studied polymorphisms, five are in strong linkage disequilibrium forming onesingle haplotype block. Though the global haplotype analysis with these five SNPs was not significant, haplotype analysis using all six SNPs yielded a global P value of .033, even after adjusting for age. These findings support the importance of dopamine receptor gene polymorphisms in alcoholism. Further studies to replicate these findings in different populations are needed to confirm these results.