A Complex Interplay of DJ-1, LRRK2, and Nrf2 in the Regulation of Mitochondrial Function in Cypermethrin-Induced Parkinsonism.

Cypermethrin impairs mitochondrial function, induces redox imbalance, and leads to Parkinsonism in experimental animals. Knockdown of deglycase-1 (DJ-1) gene, which encodes a redox-sensitive antioxidant protein, aggravates cypermethrin-mediated α-synuclein overexpression and oxidative alteration of proteins. DJ-1 is also reported to be essential for maintaining stability of nuclear factor erythroid 2-related factor 2 (Nrf2), shielding cells against oxidative insult. Leucine-rich repeat kinase 2 (LRRK2), another protein associated with Parkinson's disease, is also involved in regulating mitochondrial function. However, underlying molecular mechanisms remain elusive. The study intended to explore an interaction of DJ-1, LRRK2, and Nrf2 in the regulation of mitochondrial function in cypermethrin-induced Parkinsonism. Small interfering RNA-mediated knockdown of DJ-1 and LRRK2 gene and pharmacological activation of Nrf2 were performed in rats and/or human neuroblastoma cells with or without cypermethrin. Indexes of oxidative stress, mitochondrial impairment, and Parkinsonism along with α-synuclein expression, post-translational modification, and aggregation were measured. DJ-1 gene knockdown exacerbated cypermethrin-induced increase in oxidative stress and intrinsic apoptosis and reduction in expression of mitochondrial antioxidant proteins via inhibiting nuclear translocation of Nrf2. Additionally, cypermethrin-induced oxidative stress, mitochondrial impairment, and α-synuclein expression and aggregation were found to be suppressed by LRRK2 gene knockdown, by promoting Nrf2 nuclear translocation and expression of mitochondrial antioxidant proteins. Furthermore, Nrf2 activator, sulforaphane, ameliorated cypermethrin-induced mitochondrial impairment and oxidative stress and provided protection against dopaminergic neuronal death. The findings indicate that DJ-1 and LRRK2 independently alter Nrf2-mediated changes and a complex interplay among DJ-1, LRRK2, and Nrf2 exists in the regulation of mitochondrial function in cypermethrin-induced Parkinsonism.

Deferoxamine Ameliorates Cypermethrin-Induced Iron Accumulation and Associated Alterations.

Iron is widely linked with the onset and development of Parkinson's disease (PD). Accumulation of iron induces free radical generation and promotes α-synuclein aggregation, oxidative stress, and autophagy impairment. Deferoxamine, an iron chelator, is shown to ameliorate iron dyshomeostasis in rodents and humans. However, the role of deferoxamine in cypermethrin-induced iron accumulation is not yet known. Although an iron accumulation and impaired chaperone-mediated autophagy (CMA) contribute to PD, a link between the two is not yet widely understood. Current study is undertaken to explore the possible association between an iron accumulation and CMA in cypermethrin model of PD in the presence of deferoxamine. Level of iron, iron transporter proteins, oxidative stress, and CMA proteins along with indicators of Parkinsonism were measured. Deferoxamine attenuated cypermethrin-induced iron accumulation and number of iron-positive cells and ameliorated the demise of dopaminergic cells and dopamine content. Deferoxamine significantly normalizes cypermethrin-induced changes in iron transporter proteins, α-synuclein, lysosome-associated membrane protein-2A, and oxidative stress. The results demonstrate that deferoxamine ameliorates cypermethrin-induced iron dyshomeostasis and impairment in CMA.

Lymphocytic emperipolesis in breast carcinoma on cytology smears-A curious finding!

In this article, we discuss an intimidating finding of lymphocytic emperipolesis which was observed in breast carcinoma cells on cytology smears.

Dyshomeostasis of Iron and Its Transporter Proteins in Cypermethrin-Induced Parkinson's Disease.

The etiology of Parkinson's disease (PD) is highly complex and is still indefinable. However, a number of studies have indicated the involvement of pesticides and transition metals. Copper, magnesium, iron, and zinc have emerged as important metal contributors. Exposure to pesticides causes an accumulation of transition metals in the substantia nigra (SN) region of the brain. The cypermethrin model of PD is characterized by mitochondrial dysfunction, autophagy impairment, oxidative stress, etc. However, the effect of cypermethrin on metal homeostasis is not yet explored. The study was designed to delineate the role of metals and their transporter proteins in cypermethrin-induced animal and cellular models of PD. The level of copper, magnesium, iron, and zinc was checked in the nigrostriatal tissue and serum by atomic absorption spectroscopy. Since cypermethrin consistently increased iron content in the nigrostriatal tissue and serum after 12 weeks of exposure, the level of iron transporter proteins, such as divalent metal transporter-1 (DMT-1), ceruloplasmin, transferrin, ferroportin, and hepcidin, and their in silico interaction with cypermethrin were checked. 3,3'-Diaminobenzidine-enhanced Perl's staining showed an elevated number of iron-positive cells in the SN of cypermethrin-treated rats. Molecular docking studies revealed a strong binding affinity between cypermethrin and iron transporter protein receptors of humans and rats. Furthermore, cypermethrin increased the expression of DMT-1 and hepcidin while reducing the expression of transferrin, ceruloplasmin, and ferroportin in the nigrostriatal tissue and human neuroblastoma cells. These observations suggest that cypermethrin alters the expression of iron transporter proteins leading to iron dyshomeostasis, which could contribute to dopaminergic neurotoxicity.

Hypertension in men - An emerging public health challenge for India: Evidence from national family health survey-4.

Background: Men in the 25-54 year age group form the major workforce in developing countries like India. The rising trend of hypertension in this age group is a growing matter of concern. Objectives: This study analyzed secondary data analysis from the National Family Health Survey-4. Methods: Men in the 25-54 age group (n = 76,410) from 640 districts of the country were included in the study. State and district-wise trends in hypertension in men along with selected individual lifestyle characteristics were displayed using a geographic information system. Results: The prevalence of hypertension among men in the age group of 25-54 was found to be 35.6% for the entire country. In urban India, the prevalence of hypertension was 38.4% (uncorrected - 40.2%) compared with 33.8% (uncorrected - 34.9%) in rural India. Among the 27,973 hypertensives, 6984 (25%) were the known hypertensives prior to the survey. Out of these only 2403 (34.4%) were taking medicines. The prevalence of tobacco use in any form among the men in this age group was 45.7% (uncorrected - 49%). Conclusion: In conclusion, the study highlights the burden of hypertension in men in the prime age group along with the alarming burden of tobacco consumption and recommends public health and policy interventions targeting both hypertension and tobacco control. It requires urgent attention and specialized strategies in tiding over this epidemic brewing in the workforce of the country.

Redox Modulation of Mitochondrial Proteins in the Neurotoxicant Models of Parkinson's Disease.

Significance: Mitochondrial proteins regulate the oxidative phosphorylation, cellular metabolism, and free radical generation. Redox modulation alters the mitochondrial proteins and instigates the damage to dopaminergic neurons. Toxicants contribute to Parkinson's disease (PD) pathogenesis in conjunction with aging and genetic factors. While oxidative modulation of a number of mitochondrial proteins is linked to xenobiotic exposure, little is known about its role in the toxicant-induced PD. Understanding the role of redox modulation of mitochondrial proteins in complex cellular events leading to neurodegeneration is highly relevant. Recent Advances: Many toxicants are shown to inhibit complex I or III and elicit free radical production that alters the redox status of mitochondrial proteins. Implication of redox modulation of the mitochondrial proteins makes them a target to comprehend the underlying mechanism of toxicant-induced PD. Critical Issues: Owing to multifactorial etiology, exploration of onset and progression and treatment outcomes needs a comprehensive approach. The article explains about a few mitochondrial proteins that undergo redox changes along with the promising strategies, which help to alleviate the toxicant-induced redox imbalance leading to neurodegeneration. Future Directions: Although mitochondrial proteins are linked to PD, their role in toxicant-induced parkinsonism is not yet completely known. Preservation of antioxidant defense machinery could alleviate the redox modulation of mitochondrial proteins. Targeted antioxidant delivery, use of metal chelators, and activation of nuclear factor erythroid 2-related factor 2, and combinational therapy that encounters multiple free radicals, could ameliorate the redox modulation of mitochondrial proteins and thereby PD progression. Antioxid. Redox Signal. 38, 824-852.

Prevalence and associated factors for awareness of hypertension in India: Findings from national survey-4.

Background: Despite the fact that hypertension is increasing, merely 50% are aware of the disease. Being aware of hypertension is important to control it. Aim: The study's objective was to estimate the level of hypertension awareness in India and explore its associated sociodemographic factors. Materials and Methods: The data collected in National Family Health Survey 4 (2015-2016) among men aged 15-54 years and women aged 15-49 years were analyzed. Taking awareness of hypertension as an outcome variable, descriptive analysis, and multivariable logistic regression model were performed, by gender. Results: Of 1,41,215 hypertensive individuals analyzed, 34.7% of men and 53.6% of women were aware of being hypertensive. The control among those aware was 67.1% in men and 74.6% in women. The awareness varied among states ranging from 29.6% in Chhattisgarh to 75.6% in Tamil Nadu. The multivariable logistic regression model explained the awareness of hypertension in males increased with age (odds ratios [OR]: 0.226 for 95% confidence interval [CI]: 0.139-0.366 for 25-29 years of age increased to 0.599 for 95% CI: 0.48-0.74 for 40-44 years of age), education (OR of 0.66 for 95% CI: 0.51-0.85 for primary increased to 0.69 for 95% CI: 0.54-0.89 for secondary school level), and wealth status (OR of 0.407 for 95% CI: 0.309-0.535 for poor wealth quintile increased to 1.030 for 95% CI: 0.863-1.230 for the richest wealth quintile). For women, the awareness increased with age (OR of 0.306 for 95% CI: 0.119- 0.791 for the age of 20-24 years increased to 0.736 for 95% CI: 0.570-0.951 for the age of 45-49 years) and wealth status (OR of 0.28 for 95% CI: 0.18-0.44 for poor wealth quintile increased to 1.262 for 95% CI: 0.859-1.855 for the richest wealth quintile). Conclusion: Improving access to hypertension screening and awareness especially among men, with lower wealth and younger age is needed.

Mucocele of the Appendix: A Presentation.

The mucocele of the appendix can be described as an obstructive dilatation of the appendix by an intraluminal accumulation of mucus. A 60-year-old diabetic male patient presented with chief complains of pain in right lower abdomen for the past 2 months which was dull in nature, not associated with fever, vomiting, diarrhea, constipation, or any urinary complains. Contrast-enhanced computed tomography (CECT) of the abdomen revealed appendiceal lumen distended, filled with fluid collection. There was abrupt narrowing seen at its junction with cecum. Features were suggestive of appendicular mucocele. The patient was taken up for exploratory laparotomy, and a distended turgid appendix, around 4 cm in diameter with dilated cecum, was found. Ileocecal resection was done followed by ileo-ascending colon side-to-side anastomosis using staplers. The histopathological examination report revealed an R0 resection. The patient was followed up for 3 years postoperatively with CECT of the abdomen and a colonoscopy yearly. There was no evidence of any recurrence in the follow-up.

Type 2 diabetes mellitus augments Parkinson's disease risk or the other way around: Facts, challenges and future possibilities.

About 10% of the adult population is living with type 2 diabetes mellitus (T2DM) and 1% of the population over 60 years of age is suffering from Parkinson's disease (PD). A school of thought firmly believes that T2DM, an age-related disease, augments PD risk. Such relationship is reflected from the severity of PD symptoms in drug naive subjects possessing T2DM. Onset of Parkinsonian feature in case controls possessing T2DM corroborates the role of hyperglycemia in PD. A few cohort, meta-analysis and animal studies have shown an increased PD risk owing to insulin resistance. High fat diet and role of insulin signaling in the regulation of sugar metabolism, oxidative stress, α-synuclein aggregation and accumulation, inflammatory response and mitochondrial function in PD models and sporadic PD further connect the two. Although little is reported about the implication of PD in hyperglycemia and T2DM, a few studies have also contradicted. Ameliorative effect of anti-diabetic drugs on Parkinsonian symptoms and vague outcome of anti-PD medications in T2DM patients also suggest a link. The article reviews the literature supporting augmented risk of one by the other, analysis of proof of the concept, facts, challenges, future possibilities and standpoint on the subject.

Knowledge, Awareness, and Practices among Consumers Regarding Trans-Fat: A Cross-Sectional Study.

Introduction: Processed and preserved food items are the major source of dietary trans fat. Despite various legal provision, public awareness toward trans fats are limited. Objective: To examine the awareness of participants about various aspects of trans fats and improving their knowledge through education. Methods: A cross sectional pre- and posttest survey was conducted online through a webinar. The questionnaire has 11 questions about trans fats. Received responses were coded. Mean and frequency of continuous data were calculated. Chi-square or t-test were used to find the difference in pre and posttest. Results: Eighty five out of 95 participants completed both pre- and posttest. The scores for each question were compared to find out awareness improvement. The question based on FSSAI showed 57% improvement while 50% in case of World Health Organization's REPLACE initiative. The difference of mean score of pretest (7.57 ± 1.8) and posttest (9.22 ± 1.37) was statistically significant. Conclusion: Nutrition education and proper labelling of food items can improve the knowledge about food ingredients and food purchasing patterns. Proper enforcement and monitoring of food items labeling guidelines can be recommended.

Ameliorative Role of Nutraceuticals on Neurodegenerative Diseases Using the Drosophila melanogaster as a Discovery Model to Define Bioefficacy.

Neurodegeneration is the destruction of neurons, and once the neurons degenerate they can't revive. This is one of the most concerned health conditions among aged population, more than ∼70% of the elderly people are suffering from neurodegeneration. Among all of the neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease (PD) and Poly-glutamine disease (Poly-Q) are the major one and affecting most of the people around the world and posing excessive burden on the society. In order to understand this disease in non-human animal models it is pertinent to examine in model organism and various animal model are being used for such diseases like rat, mice and non-vertebrate model like Drosophila. Drosophila melanogaster is one of the best animal proven by several eminent scientist and had received several Nobel prizes for uncovering mechanism of human related genes and highly efficient model for studying neurodegenerative diseases due to its great affinity with human disease-related genes. Another factor is also employed to act as therapeutic or preventive method that is nutraceuticals. Nutraceuticals are functional natural compounds with antioxidant properties and had extensively showed the neuroprotective effect in different organisms. These nutraceuticals having antioxidant properties act through scavenging free radicals or by increasing endogenous cellular antioxidant defense molecules. For the best benefit, we are trying to utilize these nutraceuticals, which will have no or negligible side effects. In this review, we are dealing with various types of such nutraceuticals which have potent value in the prevention and curing of the diseases related to neurodegeneration.HighlightsNeurodegeneration is the silently progressing disease which shows its symptoms when it is well rooted.Many chemical drugs (almost all) have only symptomatic relief with side effects.Potent mechanism of neurodegeneration and improvement effect by nutraceuticals is proposed.Based on the Indian Cuisine scientists are trying to find the medicine from the food or food components having antioxidant properties.The best model to study the neurodegenerative diseases is Drosophila melanogaster.Many nutraceuticals having antioxidant properties have been studied and attenuated various diseases are discussed.

An elderly woman with multilobulated breast mass presenting as a diagnostic dilemma: A rare case report.

A breast mass in women often presents a diagnostic challenge due to the diversity in the diagnosis. We herein report a rare variant of breast carcinoma, an invasive apocrine carcinoma (AC), in an elderly woman where the breast mass clinically mimicked phyllodes tumour. Immunohistochemistry (IHC) showed the tumour as triple-negative and also negative for androgen receptor (AR). Gross cystic disease fluid protein (GCDFP-15) was strongly and diffusely positive. It is an exceptional finding. It implies its significance as a diagnostic marker of AC of the breast. The accurate diagnostic criteria of AC are still lacking. Patients with breast lumps offer unique challenges and enormous responsibility to primary and family care physicians.

An Integrated Surgical Management for Giant Dermatofibrosarcoma Protuberans of Anterior Abdominal Wall.

Giant dermatofibrosarcoma protuberans (DFSP) is a very rare dermal sarcoma whose diagnosis and management are important because of the high local recurrence but low metastatic potential. Complete surgical excision of giant DFSP in a single stage is difficult but has a high cure rate. A 47-year-old man presented with a gradually increasing large (18 x 15 x 7 cm) DFSP in the epigastrium. A 3 cm circumferential wide local excision (WLE) with microscopic tumor-free margin confirmed by frozen section was performed. Immediate single staged tension-free primary closure of resultant defect was done on the principle of abdominal wall reconstruction (AWR) in ventral hernia repair. This technique of anterior component separation and bridge meshplasty is functional, avoids multiple surgeries, is cost-effective, and can be done in a resource-limited setting in developing countries. A multidisciplinary and integrated surgical approach to treat giant DFSP over epigastrium, by three-dimensional WLE and immediate AWR with anterior component separation technique (CST) and bridging meshplasty, can be of immense help in managing such rare cases in developing countries.

Involvement of Peroxiredoxin-3, Thioredoxin-2, and Protein Deglycase-1 in Cypermethrin-Induced Parkinsonism.

Owing to its lipophilic nature, cypermethrin makes entry into the brain through the blood-brain barrier and causes severe damage to the nigrostriatal dopaminergic neurons after prolonged exposure. Following substantial accrual in the brain, cypermethrin induces the abnormal expression and accumulation of α-synuclein. Besides, cytochrome P450 2E1 (CYP2E1) causes free radical generation leading to lipid peroxidation in toxicant-induced parkinsonism. Conversely, 4-hydroxynonenal (4-HNE), a byproduct of lipid peroxidation, is known to contribute to neuronal damage. The current investigation aimed to explicate the participation of endogenous redox-sensitive proteins in cypermethrin-induced cellular and animal models of parkinsonism. The qualitative and quantitative expressions of selected redox-sensitive proteins were evaluated employing the standard procedures. Cypermethrin reduced the expression of peroxiredoxin 3 (Prx3), thioredoxin 2 (Trx2), and protein deglycase-1 (DJ-1). Knocking down of Prx3, Trx2, or DJ-1 further reduced the level of expression in the cypermethrin-treated group. Reduction in the expression of Prx3, Trx2, or DJ-1 was found to be associated with overexpression of α-synuclein and 4-HNE modification of proteins. Besides, cypermethrin increased the expression of CYP2E1, which was not altered after Prx3 or Trx2 knockdown. However, knocking down the DJ-1 augmented the level of CYP2E1 both in the cypermethrin-treated group and its respective control. The outcomes of the study demonstrate that cypermethrin reduces the level of Prx3, Trx2, and DJ-1 proteins. While the reduction in the expression of selected redox-sensitive proteins leads to α-synuclein overexpression and 4-HNE modification of proteins, DJ-1 attenuation is also linked with increased CYP2E1 expression, which in turn could lead to oxidative stress-mediated neuronal damage.

Is Gut Dysbiosis an Epicenter of Parkinson's Disease?

Once recognized as one of the most esoteric diseases of the central nervous system, Parkinson's disease (PD) is now deemed to be a chronic illness contributed by the central, autonomic and enteric nervous systems. Most likely, an accumulation of α-synuclein in the central and enteric nervous systems is the key that supports this viewpoint. Constipation, one of the non-motor hallmarks in roughly two-third of PD patients, is regulated by the composition of gut bacteria, which is assumed to set off the enteric α-synuclein accrual. Vagus nerve is suggested to direct the signal for α-synuclein over-expression and accumulation to the brain. While trillions of microorganisms reside in the intestinal tract, only one third of the proportion inhabits evenly in all individuals. Existence of an impaired gut-microbe-brain axis consonant with dysbiosis could be an epicenter of this inexplicable disorder. Any alteration in the structure and function of the gastrointestinal tract owing to exposure of endogenous or exogenous chemicals or toxicants could lead to dysbiosis. However, inconsistency in the symptoms even after exposure to same chemical or toxicant in PD patients emphatically creates a conundrum. While the level of a few specific neurotransmitters and metabolites is influenced by microbes, implication of dysbiosis is still debatable. Nevertheless, the scientific literature is overflowing with the remarkable observations supporting the role of dysbiosis in PD. Lack of specificity to differentially diagnose PD with non-PD or PD-plus syndrome, to identify highly precise drug targets and to develop therapeutic stratagems to encounter the disease on the basis of this approach, causes us to be open-minded about the dysbiosis theory. The article reviews the facts supporting gut dysbiosis as the foremost trigger for PD onset along with disagreements.

Cypermethrin Induces the Activation of Rat Primary Microglia and Expression of Inflammatory Proteins.

Cypermethrin activates microglia, which is found to be decisive in neurodegeneration in the experimental rats. While the involvement of microglial activation in toxicant-induced neurodegeneration is reported, the effect of low concentration of cypermethrin on the expression of inflammatory proteins from the rat primary microglia is not yet properly understood. The study intended to delineate the effect of low concentration of cypermethrin on the expression and release of proteins from the microglia. Rat primary microglial cells were treated with cypermethrin to check the expression of inflammatory proteins. Cypermethrin-treated microglia conditioned media and cells were collected to measure the expression and release of inflammatory proteins. Cypermethrin augmented the protein kinase C-δ (PKC-δ), inducible nitric oxide synthase (iNOS), phosphorylated mitogen-activated protein kinase (MAPK) p38 and p42/44, matrix metalloproteinase (MMP)-3, and MMP-9 levels in the cell lysate and tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels in the microglia conditioned media. Pre-treatment with minocycline, a microglial activation inhibitor or rottlerin, a PKC-δ inhibitor, notably reduced the release of TNF-α in the conditioned media and expression of iNOS protein in the microglia. Minocycline reduced the expression of PKC-δ, phosphorylated p38 and p42/44 MAPKs, MMP-3, and MMP-9 proteins in the microglia. While cypermethrin-treated conditioned media induced the toxicity in the rat primary neurons, minocycline or rottlerin reduced the cypermethrin treated microglia conditioned media-induced toxicity. The outcomes of the present study suggest that cypermethrin activates microglia and releases TNF-α and IL-1ß as well as up-regulates the expression of PKC-δ, iNOS, phosphorylated p38 and p42/44 MAPKs, MMP-3, and MMP-9 proteins, which could contribute to neurodegeneration.

Resveratrol Regulates Nrf2-Mediated Expression of Antioxidant and Xenobiotic Metabolizing Enzymes in Pesticides-Induced Parkinsonism.

BACKGROUND: Combined maneb (MB) and paraquat (PQ), two widely used pesticides, increases oxidative stress leading to Parkinsonism. Xenobiotic metabolizing enzymes, cytochrome P450 (CYP) 2D6 and its mouse ortholog Cyp2d22 protect against Parkinsonism. Resveratrol, an antioxidant, restores antioxidant defense system through the activation of nuclear factor erythroid 2- related factor 2 (Nrf2). However, a crosstalk between Cyp2d22/CYP2D6-mediated protection and resveratrol-induced Nrf2 activation leading to neuroprotection is not yet elucidated. OBJECTIVE: The study aimed to decipher the effect of resveratrol on Nrf2 activation and expression of its downstream mediators, nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 (NQO1) and thioredoxin 1 (Trx1) along with Cyp2d22/CYP2D6 activity in combined MB and PQ mouse model of Parkinsonism and differentiated neuroblastoma cells. RESULTS: MB and PQ reduced the dopamine content (mouse) and Cyp2d22/CYP2D6 activity (mouse/neuroblastoma cells) and increased the nuclear translocation of Nrf2 and expression of NQO1 and Trx1 (both). Resveratrol ameliorated pesticides-induced changes in dopamine content and Cyp2d22/CYP2D6 activity. It was found to promote nuclear translocation of Nrf2 and expression of NQO1 and Trx1 proteins. Since Cyp2d22/CYP2D6 inhibitor (ketoconazole/quinidine) per se reduced Cyp2d22/CYP2D6 activity and dopamine content, it was found to substantially increase the pesticides-induced reduction in Cyp2d22/CYP2D6 activity and dopamine content. Inhibitors normalized the pesticides induced changes in Nrf2 translocation and NQO1 and Trx1 levels in pesticides treated groups. CONCLUSION: The results suggest that resveratrol promotes the catalytic activity of xenobiotic metabolizing enzyme, Cyp2d22/CYP2D6, which partially contributes to Nrf2 activation in pesticides- induced Parkinsonism.

A bael (Aegle marmelos) in rectum presenting with bowel obstruction in an elderly man.

A case of bowel obstruction resulting from bael fruit (Aegle marmelos) in the rectum is described in an Indian Hindu elderly man. To our knowledge, this is probably the first reported case with such a presentation in available literature. Dilemma at unsuspecting clinical history and finding of clinical examination and imaging evaluation made the case more interesting and challenging to manage. The case also highlights the need for awareness, education about prevailing unregulated practice of traditional herbal medical therapy leading to disastrous consequences.

A general overview of mucocele of appendix.

Mucocele of the appendix is a very rare disease entity that often discovered incidentally during surgery. It can result from both non-neoplastic and neoplastic lesions and histopathological examination is needed for confirmation. Failure to make an early preoperative diagnosis may results in its rapture and spillage of mucin contents into the peritoneal cavity leading to a disastrous complication of pseudomyxoma peritonei (PMP) that has a very bad prognosis. A clear pathological terminology and management strategies of appendiceal mucocele (AM) is lacking. This literature review aims to derive detailed information related to clinical significance of AM to avoid complication of PMP and plan appropriately during surgery according to the current evidence. The relevant articles from scientific databases such as Medline, PubMed, Google Scholar were searched and extracted using the keywords "mucocele appendix" "cystadenoma%". Data based on epidemiology, clinical manifestations, complications, pathology, diagnostic work up and management were analyzed and summarized. A meticulous surgical excision is the mainstay of treatment and open surgical approach is still preferred over laparoscopy. Preoperative diagnosis of AM is very imperative as it may harbour neoplasm and can be made utilising the imaging tools like computed tomography and ultrasonography. Primary care physicians can have a crucial role in making early detection and timely referral for appropriate management in order to avoid complications. After appendectomy, 5-year survival rate for the simple AM is 91%-100% but it reduces to 25% for the malignant AM.