Avninder Singh

Neuroprotective role of Convolvulus pluricaulis on aluminium induced neurotoxicity in rat brain

AIM OF THE STUDYnConvolvulus pluricaulis (Convolvulaceae) has long been used as traditional herbal medicine in India as nerve tonic. We investigated neuroprotective effects of aqueous extract from Convolvulus pluricaulis (CP) against aluminium chloride induced neurotoxicity in rat cerebral cortex.nnnMATERIAL, METHOD AND RESULTnDaily administration of CP (150 mg/kg) for 3 months along with aluminium chloride (50 mg/kg) decreased the elevated enzymatic activity of acetylcholine esterase and also inhibited the decline in Na(+)/K(+)ATPase activity which resulted from aluminium intake. Beside, preventing accumulation of lipid and protein damage, changes in the levels of endogenous antioxidant enzymes associated with aluminium administration were also rectified. Oral administration of CP preserved the mRNA levels of muscarinic receptor 1 (M1 receptor), choline acetyl transferase (ChAT) and Nerve Growth Factor-Tyrosine kinase A receptor (NGF-TrkA). It also ameliorated the upregulated protein expression of cyclin dependent kinase5 (Cdk5) induced by aluminium. The potential of CPE to inhibit aluminium induced toxicity was compared with rivastigmine tartrate (1mg/kg), which was taken as standard. The potential of the extract to prevent aluminium-induced neurotoxicity was also reflected at the microscopic level, indicative of its neuroprotective effects.nnnCONCLUSIONnConvolvulus pluricaulis possesses neuroprotective potential, thus validating its use in alleviating toxic effects of aluminium.

Genome-wide analysis of chromosomal alterations in patients with esophageal squamous cell carcinoma exposed to tobacco and betel quid from high-risk area in India

Genomic alterations such as chromosomal amplifications, deletions and loss of heterozygosity play an important role in the pathogenesis and progression of cancer. Environmental risk factors contribute to the development and progression of tumors by facilitating the loss of tumor suppressor genes and amplification of oncogenes. In this current study, Affymetrix 10K single nucleotide polymorphism (SNP) arrays were used to evaluate genomic alterations in 20 pairs of matched germ-line and tumor DNA obtained from patients with esophageal squamous cell carcinoma (ESCC) from high-risk area of India where tobacco, betel quid and alcohol use are widespread. Twenty-two amplified regions and 16 deleted regions identified across chromosomal arms were biologically relevant. The candidate genes located at amplified regions of chromosomes or low-level gain regions such as PLA2G5 (1p36-p34), COL11A1 (1p21), KCNK2 (1q41), S100A3 (1q21), ENAH (1q42.12), RGS1 (1q31), KCNH1 (1q32-q41), INSIG2 (2q14.1), FGF12 (3q28), TRIO (5p15.2), RNASEN (5p15.2), FGF10 (5p13-p12), EDN1(6p24.1-p22.3), SULF1 (8q13.2-13.3), TLR4 (9q32-q33), TNC (9q33), NTRK2 (9q22.1), CD44 (11p13), NCAM1 (11q23.1), TRIM29 (11q22-q23), PAK1 (11q13-q14) and RAB27A (15q15-q21.1), are found to be associated with cellular migration and proliferation, tumor cell metastasis and invasion, anchorage independent growth and inhibition of apoptosis. The candidate genes located at deleted regions of chromosomes, such as FBLN2 (3p25.1), WNT7A (3p25), DLC1 (8p22), LZTS1 (8p22), CDKN2A (9p21), COL4A1 (13q34), CDK8 (13q12) and DCC (18q21.3), are found to be associated with the suppression of tumor. The suggested candidate genes were mostly involved in potential signaling pathways such as focal adhesion (COL4A1), tight junction (CLDN10), MAPK signaling pathway (FGF12) and neuroactive ligand receptor interaction pathway (CCKAR). Expression of FGF12 and COL4A1 was validated by tissue microarray. These unique copy number alteration profiles should be taken into consideration when developing biomarkers for the early detection of ESCC in high-risk areas of India in association with tobacco and betel quid use.

Evidence for involvement of Th17 type responses in post kala azar dermal leishmaniasis (PKDL).

Background Post kala-azar dermal leishmaniasis (PKDL), a dermal sequel of visceral leishmaniasis, caused by Leishmania donovani, constitutes an important reservoir for the parasite. Parallel functioning of counter acting immune responses (Th1/Th2) reflects a complex immunological scenario, suggesting the involvement of additional regulatory molecules in the disease pathogenesis. Methodology/Principal Findings In the present study, human cytokine/chemokine/receptor specific cDNA array technique was employed to identify modulations in gene expression of host immuno-determinants during PKDL, followed by evaluation of Th17 type responses by analyzing mRNA and protein expression of Th17 markers (IL-23, IL-17, RORγt) and performing functional assays using Leishmania antigen (TSLA) or recombinant (rec)IL-17. Array analysis identified key immuno-regulatory molecules including cytokines (TNF-α, IFN-γ, IL-10, IL-17), chemokines (MCP-1, MIP-1α), apoptotic molecules (FasL, TRAIL, IRF-1) and receptors (CD40, Fas). Up regulation in lesional expression of Th17 markers was observed during PKDL compared to control (IL-17 and IL-23, Pu200a=u200a0.0008; RORγt, Pu200a=u200a0.02). In follow-up samples, chemotherapy significantly down regulated expression of all markers. In addition, lesional expression of IL-17 was confirmed at protein level by Immuno-histochemistry. Further, systemic presence of Th17 responses (IL-17 and IL-23) was observed in plasma samples from PKDL patients. In functional assays, TSLA stimulated the secretion of IL-17 and IL-23 from PBMCs of PKDL patients, while recIL-17 enhanced the production of TNF-α as well as nitric oxide (NO) in PKDL compared to control (TNF-α, Pu200a=u200a0.0002; NO, Pu200a=u200a0.0013). Further, a positive correlation was evident between lesional mRNA expression of IL-17 and TNF-α during PKDL. Conclusion/Significance The results highlight key immune modulators in PKDL and provide evidence for the involvement of Th17 type responses in the disease pathogenesis.

Supplementation of Convolvulus pluricaulis attenuates scopolamine-induced increased tau and Amyloid precursor protein (AβPP) expression in rat brain

Aim: Scopolamine is known to produce amnesia due to blockade of the cholinergic neurotransmission. The present study investigated the potential of Convolvulus pluricaulis (CP) to attenuate scopolamine (2 mg/kg, i.p) induced increased protein and mRNA levels of tau, amyloid precursor protein (AβPP), amyloid β (Aβ) levels and histopathological changes in rat cerebral cortex. Materials and Methods: The study was conducted on male Wistar rats (250 ± 20 g) divided into four groups of eight animals each. Groups 1 and 2 served as controls receiving normal saline and scopolamine for 4 weeks, respectively. Group 3 received rivastigmine (standard) and group 4 received aqueous extract of CP simultaneously with scopolamine. Western blot and RT-PCR analysis were used to evaluate the levels of protein and mRNA of amyloid precursor protein (AβPP) and tau in rat cortex and ELISA was used to measure the amyloid β (Aβ) levels. Histopathology was also performed on cortical section of all groups. Result: Oral administration of CP extract (150 mg/kg) to scopolamine treated rats reduced the increased protein and mRNA levels of tau and AβPP levels followed by reduction in Aβ levels compared with scopolamine treated group. The potential of extract to prevent scopolamine neurotoxicity was reflected at the microscopic level as well, indicative of its neuroprotective effects. Conclusion: CP treatment alleviated neurotoxic effect of scopolamine reflects its potential as potent neuroprotective agent.

Novel diallyldisulfide analogs ameliorate cardiovascular remodeling in rats with L-NAME-induced hypertension.

Diallyldisulfide (DADS), an active principle of garlic (Allium sativum) is known for its antihypertensive properties. The present study was designed to evaluate the effect of novel DADS analogs, against L-NAME induced hypertension in Wistar rats. The daily administration of L-NAME (50mg/kg) for six weeks along with DADS analogs (20 mg/kg) significantly decreased the elevated systolic blood pressure (SBP) and the activity of angiotensin converting enzyme (ACE) and also inhibited the decline in nitrite/nitrate (NO(x)) concentrations and cyclic guanosine monophosphate (cGMP) levels. Adverse changes such as lipid peroxidation, protein damage and a decrease in the levels of antioxidant enzymes, were rectified after the administration of DADS analogs. Oral administration of DADS analogs preserved the expression of endothelial nitric oxide synthase (eNOS). The ability of the DADS analogs to inhibit L-NAME induced hypertension was compared with Enalapril (15 mg/kg), which was taken as a standard. The DADS analogs prevented L-NAME-induced cardio toxicity, which was also reflected at the microscopic level indicative of its cardio protective effects. DADS analogs induced vasorelaxation was completely abolished by the removal of the endothelium or by pre-treatment with L-NAME, an inhibitor of nitric oxide synthase. DADS analogs inhibited the calcium influx induced by phenylephrine (0.3 μM) and high K(+) (60mM) and this effect was completely abolished by pretreatment of L-NAME. Taken together, our results show that the DADS analogs induce vasorelaxation and have antihypertensive properties, which may be mediated through activation of eNOS.

Leiomyoma cutis: A clinicopathological series of 37 cases

Background: Cutaneous leiomyomas are benign smooth muscle tumors that comprise three distinct types such as piloleimyoma, angioleiomyoma, and genital leiomyoma. Aim: The objective of this study was to report a series of cases seen in last 8 years in a tertiary care hospital in north India and to discuss their clinicopathologic findings. Material and Methods: Paraffin-embedded blocks of cases reported as cutaneous leiomyoma from 1999 to 2007 were retrieved from the Institute of Pathology, New Delhi, and their clinical parameters were noted. Their histopathological features were reviewed on hematoxylin-eosin stained slides. Immunohistochemistry was performed where necessary. Results: Twenty-seven cases of piloleiomyoma, three cases of angioleiomyoma, five breast leiomyomas, and two scrotal leiomyomas were seen in patients ranging from 21 to 65 years of age, with an average of 38.2 years at presentation. There was a male predominance with 26 males and 11 females (M:F = 2.2:1). Solitary lesions (n = 21) were more common than multiple ( n = 16). The trunk and upper limbs were involved most commonly, comprising 23 of 37 (62.2%) cases. This was followed by lower limb, face, breast, and scrotum. Conclusion: Cutaneous leiomyomas are rare lesions and form an important clinical differential diagnosis of painful papulonodules. These must be biopsied in order to differentiate them from other spindle cell lesions.

Disseminated Emmonsia pasteuriana infection in India: a case report and a review

We report here the first case of disseminated Emmonsia pasteuriana infection in a patient with AIDS in India. The patient presented with weight loss, dyspnoea, left‐sided chest pain and multiple non‐tender skin lesions over face and body for 3 months. Disseminated emmonsiosis was diagnosed on microscopic examination and fungal culture of skin biopsy and needle aspirate of lung consolidation. It was confirmed by sequencing internal transcribed spacer region of rDNA, beta tubulin, actin, and intein PRP8. The patient responded to amphotericin B and itraconazole therapy.

Primary cutaneous adenoid cystic carcinoma with distant metastasis: a case report and brief literature review.

Primary adenoid cystic carcinoma (PCACC) of skin is a rare tumor, and those who show distant metastasis are even rarer. We report a case of PCACC on the face of a 55-year-old man who showed bilateral lung metastasis and on palliative chemotherapy showed significant regression of the primary tumor. The patient was alive at a 15-month follow-up. A brief literature review of the eight cases including ours is described.

Histopathological characteristics of post kala-azar dermal leishmaniasis: A series of 88 patients

BACKGROUNDnPost kala azar dermal leishmaniasis (PKDL) is a sequel to visceral leishmaniasis or kala azar seen predominantly in the Indian subcontinent and Africa. Histopathological descriptions of the condition are limited.nnnMETHODSnBiopsies of 88 skin and 16 mucosal lesions were evaluated for histopathological findings on formalin-fixed, paraffin-embedded tissues.nnnRESULTSnThere were 71 (80.7%) males and 17 (19.3%) females with a mean age of 24.8 and 28.5 years, respectively. A past history of kala azar was present in 64 (72.7%) patients and post kala azar dermal leishmaniasis developed a mean of 6.2 years after visceral leishmaniasis. Of the biopsies studied, the clinical lesions were macular in 14 (15.9%), papulo-nodular in 32 (36.3%) and showed both macules and papulo-nodules in 42 (47.8%). Follicular plugging was a common epidermal finding. A clear Grenz zone was frequently noted. The dermal infiltrates were arranged mainly in three patterns: superficial perivascular infiltrates in 16 (18.1%), perivascular and perifollicular infiltrates in 24 (27.3%) and diffuse infiltrates in 41 (46.6%) biopsies. Leishman-Donovan (LD) bodies were noted in 13 (44.9%) of 69 cases on slit-skin smear and in 25 (28.4%) of 88 biopsies. In 16 patients, where both skin and mucosal biopsies were available, LD bodies were identified in 10 (62.5%) mucosal biopsies as compared to 3 (18.7%) skin biopsies.nnnLIMITATIONSnThe retrospective nature of the study and the lack of controls were limitations.nnnCONCLUSIONnThe various histomorphological patterns of post kala azar dermal leishmaniasis are a useful clue to the diagnosis even when LD bodies have not been detected. This study also suggests that LD bodies are more frequently seen in mucosal biopsies in comparison to cutaneous biopsies.

Syringocystadenoma papilliferum on the thigh: an unusual location.

A 28-year-old man presented with a partially eroded growth on the back of his right thigh for the last 15 years. Tuberculosis verrucosa cutis and pyogenic granuloma were suspected on clinical examination. Histopathological examination revealed syringocystadenoma papilliferum (SCAP). SCAP is rare on the thigh and a review of the English literature revealed eight cases. Non-descript clinical presentation in an unusual location and the rare linear and segmental variants lead to misdiagnosis. Onset at puberty should alert one to the possibility of the unusual location of SCAP.